Journal: Eur Heart J Cardiovasc Pharmacother

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Abstract

Aspirin-free antiplatelet regimens after PCI: insights from the GLOBAL LEADERS trial and beyond.

Wang R, Wu S, Gamal A, Gao C, ... Serruys PW, Garg S
Historically, aspirin has been the primary treatment for the prevention of ischemic events in patients with coronary artery disease. For patients undergoing percutaneous coronary intervention (PCI) standard treatment has been 12-months of dual anti-platelet therapy (DAPT) with aspirin and clopidogrel, followed by aspirin monotherapy; however, DAPT is undeniably associated with an increased risk of bleeding. For over a decade novel P2Y12 inhibitors, which have increased specificity, potency and efficacy have been available, prompting studies which have tested whether these newer agents can be used in aspirin-free anti-platelet regimens to augment clinical benefits in patients post-PCI. Among these studies, the GLOBAL LEADERS trial is the largest by cohort size, and so far has provided a wealth of evidence in a variety of clinical settings and patient groups. This article summarizes the state-of-the-art evidence obtained from the GLOBAL LEADERS and other trials of aspirin-free strategies.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J Cardiovasc Pharmacother: 29 Apr 2021; epub ahead of print
Wang R, Wu S, Gamal A, Gao C, ... Serruys PW, Garg S
Eur Heart J Cardiovasc Pharmacother: 29 Apr 2021; epub ahead of print | PMID: 33930107
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Abstract

Anticoagulation in atrial fibrillation and liver disease: a pooled-analysis of > 20000 patients.

Chen S, Pürerfellner H, Meyer C, Sommer P, ... Chun JKR, Schmidt B
Aims
Anticoagulation for atrial-fibrillation (AF) patients with liver-disease represents a clinical dilemma. We sought to evaluate the efficacy/safety of different anticoagulation, i.e. vitamin-K-antagonist (VKA) and non-VKA oral-anticoagulants (NOACs) in such patient group.
Methods and results
This was a pooled-analysis enrolling up-to-date clinical data. Two subsets: subset A (VKA vs. Non-Anticoagulation) and subset B (NOACs vs. VKA) were pre-specified. The study outcomes were ischemic-stroke(IS)/thromboembolism(TE), major-bleeding (MB), intracranial-bleeding (ICB), gastrointestinal-bleeding (GIB) and all-cause mortality.A total of 20,042 patients\' data were analyzed (subset A: N = 10275, subset B: N = 9767). Overall mean age: 71±11 years, mean CHA2DS2-VASc score: 4.0±1.8, mean HAS-BLED score: 3.6±1.2. The majority of the patients had Child-Pugh category (A-B). As compared with Non-Anticoagulation, VKA seemed to reduce the risk of IS/TE (OR: 0.60, P = 0.05), but heighten the risk of all-bleeding-events including MB (OR: 2.81, P = 0.01), ICB (OR: 1.60, P = 0.01), and GIB (OR: 3.32, P = 0.01). When compared with VKA, NOACs had similar efficacy in reducing the risk of IS/TE (OR: 0.82, P = 0.64), significantly lower risk of MB (OR: 0.54, P = 0.0003) and ICB (OR: 0.35, P < 0.0001), and trend towards reduced risk of GIB (OR: 0.72, P = 0.12) and all-cause mortality (OR: 0.79, P = 0.35). The favorable effects were maintained in subgroups of individual NOAC.
Conclusions
VKA appears to reduce the risk of IS/TE but increase all-bleeding-events. NOACs have similar effect in reducing the risk of IS/TE and have significantly lower risk of MB and ICB as compared with VKA. NOACs seem to be associated with better clinical outcome than VKA in patients with mild-moderate liver disease.

© Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2021. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 18 Apr 2021; epub ahead of print
Chen S, Pürerfellner H, Meyer C, Sommer P, ... Chun JKR, Schmidt B
Eur Heart J Cardiovasc Pharmacother: 18 Apr 2021; epub ahead of print | PMID: 33871577
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Abstract

Thromboembolism and bleeding complications in anticoagulated patients with atrial fibrillation and native aortic or mitral valvular heart disease: a descriptive nationwide cohort study.

Melgaard L, Overvad TF, Jensen M, Lip GYH, Larsen TB, Nielsen PB
Aims
To describe the risks of thromboembolism and major bleeding complications in anticoagulated patients with atrial fibrillation (AF) and native aortic or mitral valvular heart disease using data reflecting clinical practice.
Methods and results
Descriptive cohort study of anticoagulated patients with incident AF and native aortic or mitral valvular heart disease, identified in nationwide Danish registries from 2000 to 2018. A total of 10 043 patients were included, of which 5190 (51.7%) patients had aortic stenosis, 1788 (17.8%) patients had aortic regurgitation, 327 (3.3%) patients had mitral stenosis, and 2738 (27.3%) patients had mitral regurgitation. At 1 year after AF diagnosis, the risk of thromboembolism was 4.6% in patients with mitral stenosis taking a vitamin K antagonist (VKA), and 2.6% in patients with aortic stenosis taking a VKA or non-vitamin K antagonist oral anticoagulant (NOAC). For patients with aortic or mitral regurgitation, the risks of thromboembolism ranged between 1.5%-1.8% in both treatment groups. For the endpoint of major bleeding, the risk was ∼5.5% in patients with aortic stenosis or mitral stenosis treated with a VKA, and 3.3-4.0% in patients with aortic or mitral regurgitation. For patients treated with a NOAC, the risk of major bleeding was 3.7% in patients with aortic stenosis and ∼2.5% in patients with aortic or mitral regurgitation.
Conclusion
When using data reflecting contemporary clinical practice, our observations suggested that 1 year after a diagnosis of AF, anticoagulated patients with aortic or mitral valvular heart disease had dissimilar risk of thromboembolism and major bleeding complications. Specifically, patients with aortic stenosis or mitral stenosis were high-risk subgroups. This observation may guide clinicians regarding intensity of clinical follow-up.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 08 Apr 2021; 7:f101-f110
Melgaard L, Overvad TF, Jensen M, Lip GYH, Larsen TB, Nielsen PB
Eur Heart J Cardiovasc Pharmacother: 08 Apr 2021; 7:f101-f110 | PMID: 32003787
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Abstract

All-cause mortality, stroke, and bleeding in patients with atrial fibrillation and valvular heart disease.

Strange JE, Sindet-Pedersen C, Staerk L, Grove EL, ... Gislason GH, Olesen JB
Aims 
To compare the risk of all-cause mortality, stroke, and bleeding in patients with atrial fibrillation (AF) and valvular heart disease (VHD) treated with vitamin K antagonist (VKA) or factor Xa-inhibitors (FXa-I; rivaroxaban and apixaban).
Methods and results 
We cross-linked data from Danish nationwide registries identifying patients with AF and VHD (aortic stenosis/insufficiency, mitral insufficiency, bioprosthetic heart valves, mitral-, and aortic valve repair) initiating VKA or FXa-I between January 2014 and June 2017. Outcomes were all-cause mortality, stroke, and bleeding. Using cause-specific Cox regression, we reported the standardized absolute 2-year risk of the outcomes and absolute risk differences (ARD). We identified 1115 (41.7%), 620 (23.1%), and 942 (35.2%) patients initiating treatment with VKA, rivaroxaban, and apixaban, respectively. The standardized absolute risk (95% confidence interval) of all-cause mortality associated with VKA treatment was 34.1% (30.4-37.8%) with corresponding ARD for FXa-I of -2.7% (-6.7% to 1.4%). The standardized absolute risk of stroke for VKA was 3.8% (2.2-5.4%) with corresponding ARD for FXa-I of -0.1% (-2.0% to 1.8%). The standardized risk of bleeding for VKA was 10.4% (7.2-12.9%) with corresponding ARD for FXa-I of -2.0% (-5.1% to 1.1%). The risk of bleeding was significantly reduced in subgroup analyses of apixaban compared with VKA [ARD: -3.9% (-7.0% to -0.9%)] and rivaroxaban [ARD: -5.6% (-9.5% to -1.7%)].
Conclusion 
In this nationwide cohort study, there were no significant differences in the risks of all-cause mortality, stroke, and bleeding in patients with AF and VHD treated with VKA compared with FXa-I.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 08 Apr 2021; 7:f93-f100
Strange JE, Sindet-Pedersen C, Staerk L, Grove EL, ... Gislason GH, Olesen JB
Eur Heart J Cardiovasc Pharmacother: 08 Apr 2021; 7:f93-f100 | PMID: 32065652
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Abstract

Impact of liver disease on oral anticoagulant prescription and major adverse events in patients with atrial fibrillation: analysis from a population-based cohort study.

Proietti M, Marzona I, Vannini T, Colacioppo P, ... Lip GYH, Roncaglioni MC
Aims 
Data on the impact of liver disease (LD) in patients with atrial fibrillation (AF) and the role of oral anticoagulant (OAC) drugs for stroke prevention are limited.
Methods and results 
A retrospective observational population-based cohort study on the administrative health databases of Lombardy region Italy. All AF patients ≥40 years admitted to hospital from 2000 to 2018 were considered. Atrial fibrillation and LD diagnosis were established using ICD9-CM codes. Use of OAC was determined with Anatomical Therapeutic Chemical codes. Primary study outcomes were stroke, major bleeding, and all-cause death. Among 393 507 AF patients, 16 168 (4.1%) had concomitant LD. Liver disease AF patients were significantly less treated with OAC. Concomitant LD was associated with an increased risk in all the study outcomes [hazard ratio (HR): 1.18, 95% confidence interval (CI): 1.11-1.25 for stroke; HR: 1.57, 95% CI: 1.47-1.66 for major bleeding; HR: 1.41, 95% CI: 1.39-1.44 for all-cause death]. Use of OAC in patients with AF and LD resulted in a reduction in stroke (HR: 0.80, 95% CI: 0.70-0.92), major bleeding (HR: 0.86, 95% CI: 0.74-0.99), and all-cause death (HR: 0.77, 95% CI: 0.73-0.80), with similar results according to subgroups. A net clinical benefit (NCB) analysis suggested a positive benefit/risk ratio in using OAC in AF patients with LD (NCB: 0.408, 95% CI: 0.375-0.472).
Conclusion
In AF patients, concomitant LD carries a significantly higher risk for all clinical outcomes. Use of OAC in AF patients with LD was associated with a significant favourable benefit/risk ratio, even in high-risk patient subgroups.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 08 Apr 2021; 7:f84-f92
Proietti M, Marzona I, Vannini T, Colacioppo P, ... Lip GYH, Roncaglioni MC
Eur Heart J Cardiovasc Pharmacother: 08 Apr 2021; 7:f84-f92 | PMID: 32129845
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Abstract

Motivational Interviewing to Support Oral AntiCoagulation adherence in patients with non-valvular Atrial Fibrillation (MISOAC-AF): a randomized clinical trial.

Tzikas A, Samaras A, Kartas A, Vasdeki D, ... Karvounis H, Giannakoulas G
Aims
We aimed to assess the impact of an educational, motivational intervention on the adherence to oral anticoagulation (OAC) in patients with non-valvular atrial fibrillation (AF).
Methods and results
Hospitalized patients with non-valvular AF who received OAC were randomly assigned to usual medical care or a proactive intervention, comprising motivational interviewing, and tailored counselling on medication adherence. The primary study outcome was adherence to OAC at 1 year, which was evaluated according to proportion of days covered (PDC) by OAC regimens and was assessed through nationwide registers of prescription claims. Secondary outcomes included the rate of persistence to OAC, gaps in treatment, and clinical events. A total of 1009 patients were randomized, 500 in the intervention group and 509 in the control group. At 1-year follow-up, 77.2% (386/500) of patients in the intervention group were adherent (PDC > 80%), compared with 55% (280/509) in the control group [adjusted odds ratio (aOR) 2.84, 95% confidence interval (CI) 2.14-3.75; P < 0.001]. Mean PDC ± standard deviation was 0.85 ± 0.26 and 0.75 ± 0.31, respectively (P < 0.001). Patients that received the intervention were more likely to persist in their OAC therapy at 1 year (aOR 2.42, 95% CI 1.71-3.41; P < 0.001). Usual medical care was associated with more major (≥3 months) treatment gaps (aOR 2.39, 95% CI 1.76-3.26; P < 0.001). Clinical events over a median follow-up period of 2 years did not differ among treatment groups.
Conclusion
In patients receiving OAC therapy for non-valvular AF, a multilevel motivational intervention significantly improved medication adherence and rate of therapy persistence, and reduced major gaps in treatment. No significant impact on clinical outcomes was observed.
Trial registration number
NCT02941978.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 08 Apr 2021; 7:f63-f71
Tzikas A, Samaras A, Kartas A, Vasdeki D, ... Karvounis H, Giannakoulas G
Eur Heart J Cardiovasc Pharmacother: 08 Apr 2021; 7:f63-f71 | PMID: 32339234
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Impact:
Abstract

Long-term persistence and adherence with non-vitamin K oral anticoagulants in patients with atrial fibrillation and their associations with stroke risk.

Komen JJ, Heerdink ER, Klungel OH, Mantel-Teeuwisse AK, ... Wettermark B, Hjemdahl P
Aims 
Studies on adherence and persistence with non-vitamin K oral anticoagulant (NOAC) treatment have relied on data from the early years of NOAC availability. We aimed to study long-term adherence and persistence with NOACs and their association with stroke risk.
Methods and results 
From the Stockholm Healthcare database, we included 21 028 atrial fibrillation patients claiming a first NOAC prescription from July 2011 until October 2018, with more than 1000 patients having more than 5 years of follow-up (median: 2.0, interquartile range: 1.0-3.2). Persistence rates, defined as continuing to claim NOAC prescriptions within a 90-day gap, decreased to 70% at the end of follow-up. However, 85% of the patients were treated at the end of the study due to reinitiations. Adherence, calculated as medication possession rate (MPR) in 3 and 6-month intervals among persistent users, remained stable at 90%, with 75% of patients having an MPR >95% throughout the study period. Using a case-control design, we calculated associations of persistence and adherence with stroke risk, adjusting for potential confounders. The outcome was a composite of ischaemic or unspecified stroke and transient ischaemic attack. Non-persistence and poor adherence were both associated with increased stroke risk [non-persistence adjusted odds ratio (aOR): 2.05; 95% confidence interval (CI): 1.49-2.82, 1% reduction MPR aOR: 1.03; CI: 1.01-1.05]. There was no association between non-persistence or poor adherence and the falsification endpoints; fractions and respiratory infections, indicating no \'healthy-adherer\' effect.
Conclusion 
Persistence rates decreased slowly over time, but persistent patients had high adherence rates. Both non-persistence and poor adherence were associated with an increased stroke risk.

© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J Cardiovasc Pharmacother: 08 Apr 2021; 7:f72-f80
Komen JJ, Heerdink ER, Klungel OH, Mantel-Teeuwisse AK, ... Wettermark B, Hjemdahl P
Eur Heart J Cardiovasc Pharmacother: 08 Apr 2021; 7:f72-f80 | PMID: 32324233
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Abstract

Assessing absolute stroke risk in patients with atrial fibrillation using a risk factor-based approach.

Lee CJ, Toft-Petersen AP, Ozenne B, Phelps M, ... Torp-Pedersen C, Gerds TA
Aim
To assess the risk of stroke and thromboembolism in patients with atrial fibrillation (AF) based on risk factor combinations of the CHA2DS2-VASc score.
Methods and results
Using nationwide Danish registries, patients with AF were included from 1997 to 2015 in this retrospective observational study. A multiple logistic regression, including interactions of history of stroke with age at AF, calendar year of AF, and the CHA2DS2-VASc score risk factors (congestive heart failure, hypertension, diabetes, vascular disease, and female sex) were used to predict the personalized risks of stroke within 1 year. A total of 147 842 patients with AF were included in the study cohort (median age 76 years, range 20-100 years, 51% females). Within the first year, 6% of the cohort were diagnosed with stroke. The predicted personalized 1-year absolute risk of stroke varied widely within each CHA2DS2-VASc score. To estimate the personalized risk of stroke an online calculator was created, the Calculator of Absolute Stroke Risk (CARS), which allows calculation of all the possible combinations of the CHA2DS2-VASc score (https://hjerteforeningen.shinyapps.io/riskvisrr/).
Conclusion
Calculation of the individual risk using a risk factor-based approach as opposed to using average risk for a particular CHA2DS2-VASc score can improve risk estimates. Furthermore, CARS can assist in the communication of the stroke risk for a more evidence-based shared decision-making of whether to initiate oral anticoagulation therapy.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 08 Apr 2021; 7:f3-f10
Lee CJ, Toft-Petersen AP, Ozenne B, Phelps M, ... Torp-Pedersen C, Gerds TA
Eur Heart J Cardiovasc Pharmacother: 08 Apr 2021; 7:f3-f10 | PMID: 32531029
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Impact:
Abstract

Edoxaban for stroke prevention in atrial fibrillation in routine clinical care: 1-year follow-up of the prospective observational ETNA-AF-Europe study.

de Groot JR, Weiss TW, Kelly P, Monteiro P, ... De Caterina R, Kirchhof P
Aims
Non-vitamin K oral anticoagulants are safe and effective for stroke prevention in patients with atrial fibrillation (AF). Data on the safety and efficacy of edoxaban in routine care are limited in Europe. We report 1-year outcomes in patients with AF treated with edoxaban in routine care.
Methods and results
ETNA-AF-Europe is a prospective, multicentre, post-authorization, observational study enrolling patients treated with edoxaban in 10 European countries, the design of which was agreed with the European Medicines Agency as part of edoxaban\'s post-approval safety plan. Altogether 13 092 patients in 852 sites completed the 1-year follow-up [mean age: 73.6 ± 9.5 years; 57% male, mean follow-up: 352 ± 49 days (median: 366 days)]. Most patients had associated comorbidities (mean CHA2DS2-VASc score: 3.1 ± 1.4). Stroke or systemic embolism was reported in 103 patients (annualized event rate: 0.82%/year), and major bleeding events were reported in 132 patients (1.05%/year). Rates of intracranial haemorrhage were low [30 patients (0.24%/year)]. Death occurred in 442 patients (3.50%/year); cardiovascular (CV) death occurred in 206 patients (1.63%/year). The approved dosing of edoxaban was chosen in 83%. All-cause and CV mortality were higher in patients receiving edoxaban 30 mg vs. 60 mg, in line with the higher age and more frequent comorbidities of the 30 mg group. Major bleeding was also numerically more common in patients receiving edoxaban 30 mg vs. 60 mg.
Conclusion
The rates of stroke, systemic embolism, and major bleeding are low in this large unselected cohort of high-risk AF patients routinely treated with edoxaban.

© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J Cardiovasc Pharmacother: 08 Apr 2021; 7:f30-f39
de Groot JR, Weiss TW, Kelly P, Monteiro P, ... De Caterina R, Kirchhof P
Eur Heart J Cardiovasc Pharmacother: 08 Apr 2021; 7:f30-f39 | PMID: 32790837
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Impact:
Abstract

Patients with diabetes mellitus and atrial fibrillation treated with non-vitamin K antagonist oral anticoagulants: meta-analysis of eight outcomes in 58 634 patients across four randomized controlled trials.

Plitt A, Zelniker TA, Park JG, McGuire DK, ... Braunwald E, Giugliano RP
Aims
Concomitant atrial fibrillation (AF) and diabetes mellitus (DM) increases the risk of stroke and systemic embolic events (SEE). This meta-analysis assessed the benefit/risk balance of non-vitamin K antagonist oral anticoagulants (NOACs) vs. warfarin, and explored whether there was effect modification by DM or heterogeneity in outcomes between NOACs in patients with and without DM.
Methods and results
We performed a meta-analysis of 58 634 patients from four Phase 3 trials of NOAC vs. warfarin in patients with AF, comparing the primary outcomes of efficacy and safety and six other secondary outcomes in patients stratified by the presence of DM. Interaction testing was used to assess for heterogeneity of treatment effects. A meta-regression was performed to evaluate the influence of baseline characteristics. NOACs reduced the risk of stroke/SEE in 18 134 patients with DM [hazard ratio (HR) 0.80; 95% confidence interval (CI) (0.69-0.93), I2 3.90] to a similar degree as in 40 500 patients without DM [HR 0.82; 95% CI (0.74-0.91), I2 16.33; P-int 0.81]. There was no effect modification of DM on the relative reduction with NOACs vs. warfarin in major bleeding (DM: 0.95, 95% CI 0.75-1.20, I2 43.83; no DM: 0.83, 95% CI 0.55-1.24; I2 87.90; P-int 0.37). Intracranial haemorrhage (HRs 0.51 and 0.47, P-int 0.70) and cardiovascular death (HRs 0.87 and 0.90, P-int 0.70) were significantly reduced by NOACs in the presence or absence of DM.
Conclusion
Non-vitamin K antagonist oral anticoagulants are more effective and safer than warfarin in AF patients with or without DM. Absent contraindications, NOACs should be the anticoagulation treatment choice in patients with diabetes.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 08 Apr 2021; 7:f40-f49
Plitt A, Zelniker TA, Park JG, McGuire DK, ... Braunwald E, Giugliano RP
Eur Heart J Cardiovasc Pharmacother: 08 Apr 2021; 7:f40-f49 | PMID: 33063112
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Impact:
Abstract

Safety and efficacy of double vs. triple antithrombotic therapy in patients with atrial fibrillation with or without acute coronary syndrome undergoing percutaneous coronary intervention: a collaborative meta-analysis of non-vitamin K antagonist oral anticoagulant-based randomized clinical trials.

Gargiulo G, Cannon CP, Gibson CM, Goette A, ... Vranckx P, Valgimigli M
Aims
Safety and efficacy of antithrombotic regimens in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) may differ based on clinical presentation. We sought to compare double vs. triple antithrombotic therapy (DAT vs. TAT) in AF patients with or without acute coronary syndrome (ACS) undergoing PCI.
Methods and results
A systematic review and meta-analysis was performed using PubMed to search for non-vitamin K antagonist oral anticoagulant (NOAC)-based randomized clinical trials. Data on subgroups of ACS or elective PCI were obtained by published reports or trial investigators. A total of 10 193 patients from four NOAC trials were analysed, of whom 5675 presenting with ACS (DAT = 3063 vs. TAT = 2612) and 4518 with stable coronary artery disease (SCAD; DAT = 2421 vs. TAT = 2097). The primary safety endpoint of ISTH major bleeding or clinically relevant non-major bleeding was reduced with DAT compared with TAT in both ACS (12.2% vs. 19.4%; RR 0.63, 95% CI 0.56-0.71; P < 0.0001; I2 = 0%) and SCAD (14.6% vs. 22.0%; RR 0.68, 95% CI 0.55-0.85; P = 0.0008; I2 = 66%), without interaction (P-int = 0.54). Findings were consistent for secondary bleeding endpoints, including intra-cranial haemorrhage. In both subgroups, there was no difference between DAT and TAT for all-cause death, major adverse cardiovascular events, or stroke. Myocardial infarction and stent thrombosis were numerically higher with DAT vs. TAT consistently in ACS and SCAD (P-int = 0.60 and 0.86, respectively). Findings were confirmed by multiple sensitivity analyses, including a separate analysis on dabigatran regimens and a restriction to PCI population.
Conclusions
DAT, compared with TAT, is associated with lower bleeding risks, including intra-cranial haemorrhage, and a small non-significant excess of cardiac ischaemic events in both patients with or without ACS.

© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J Cardiovasc Pharmacother: 08 Apr 2021; 7:f50-f60
Gargiulo G, Cannon CP, Gibson CM, Goette A, ... Vranckx P, Valgimigli M
Eur Heart J Cardiovasc Pharmacother: 08 Apr 2021; 7:f50-f60 | PMID: 33119069
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Impact:
Abstract

Real-world safety and efficacy of direct oral anticoagulants in atrial fibrillation: a systematic review and meta-analysis of 605 771 patients.

Menichelli D, Del Sole F, Di Rocco A, Farcomeni A, ... Lip GYH, Pastori D
Aims
To analyse the safety and efficacy of direct oral anticoagulants (DOACs) in real-world studies including atrial fibrillation (AF) patients.
Methods and results
Systematic review and meta-analysis of observational studies including AF patients on DOACs. Primary endpoints: any, major, gastrointestinal (GI), intracranial haemorrhage (ICH), and haemorrhagic stroke (HS). Secondary endpoints: ischaemic stroke (IS), systemic embolism (SE), myocardial infarction (MI), and all-cause of death. A set of pair-wise meta-analyses using a random effect model and a random effect network meta-analysis under a Bayesian framework were performed. Prospero registration number: CRD42019137111. We included 21 studies with 605 771 AF patients. Apixaban was associated with lower major and GI bleeding compared with Rivaroxaban [hazard ratio (HR) 2.0, 95% confidence interval (CI) 1.6-2.5] and Dabigatran (HR 1.6, 95% CI 1.3-2.1). The latter drug performed better than Rivaroxaban (HR 1.2, 95% CI 1.0-1.5). Dabigatran and Apixaban had a similar association with HS, but Apixaban performed better than Rivaroxaban (HR 1.8, 95% CI 1.1-3.0). Apixaban had a similar association with Rivaroxaban and Dabigatran for ICH, the latter drug performing better than Rivaroxaban (HR 1.3, 95% CI 1.0-1.7). Rankograms showed that Apixaban was likely to be the first-choice treatment in relation to any (65%) major (100%) and GI bleeding (100%) followed by Dabigatran (46%, 100%, 99%, respectively). Dabigatran and Apixaban had similar rank as first choice for ICH (44% and 55%) and HS (52% and 48%). DOACs showed similar association with IS/SE, MI, all-cause of death.
Conclusions
Analysis of real-world studies shows significant differences for safety among DOACs.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 08 Apr 2021; 7:f11-f19
Menichelli D, Del Sole F, Di Rocco A, Farcomeni A, ... Lip GYH, Pastori D
Eur Heart J Cardiovasc Pharmacother: 08 Apr 2021; 7:f11-f19 | PMID: 33493255
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Impact:
Abstract

Renal protection in chronic heart failure: focus on sacubitril/valsartan.

Pontremoli R, Borghi C, Filardi PP
Chronic kidney disease (CKD) is highly prevalent in patients with chronic heart failure (CHF) and increases the risk of overall and cardiovascular (CV) mortality. Despite evidence supporting the effectiveness of angiotensin-converting enzyme inhibitors (ACE-I), angiotensin receptor blockers (ARB), and mineralocorticoid receptor antagonists (MRA) in decreasing mortality in patients with CHF, CKD hampers the optimization of standard pharmacologic therapy for HF. Therefore, other treatment options are needed to optimize treatment outcomes in CHF patients with CKD. The first-in-class angiotensin receptor-neprilysin inhibitor, sacubitril/valsartan, has a complementary activity that counteracts the potential unwanted long-term effects of over-activation of the renin-angiotensin-aldosterone system. Sacubitril/valsartan reduced the risk of CV mortality compared to standard therapy with an ACE-I in patients with heart failure with reduced ejection fraction (HFrEF) in the PARADIGM-HF trial and has been shown to be safe and effective in a broad range of HFrEF patients. However, data on the efficacy and tolerability of sacubitril/valsartan in patients with more advanced CKD are limited. This review discusses the evidence for the role of sacubitril/valsartan in providing additional renal benefit in patients with HFrEF. Data from clinical trials and real-world experience in patients with HFrEF and advanced CKD support the benefits of dual angiotensin/neprilysin inhibition across the breadth of kidney disease stages, including patients with significant renal impairment that was not reported in the pivotal PARADIGM-HF trial, and suggests a central role for the cardiac benefits of sacubitril/valsartan in nephroprotection.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J Cardiovasc Pharmacother: 02 Apr 2021; epub ahead of print
Pontremoli R, Borghi C, Filardi PP
Eur Heart J Cardiovasc Pharmacother: 02 Apr 2021; epub ahead of print | PMID: 33822031
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Impact:
Abstract

Spironolactone effect on the blood pressure of patients at risk of developing heart failure: an analysis from the HOMAGE trial.

Ferreira JP, Collier T, Clark AL, Mamas MA, ... Cleland JG, Zannad F
Background
Uncontrolled blood pressure (BP) increases the risk of developing heart failure (HF). The effect of spironolactone on BP of patients at risk of developing HF is yet to be determined.
Aims
To evaluate the effect of spironolactone on the BP of patients at risk for HF and whether renin can predict spironolactone`s effect.
Methods
HOMAGE (Heart OMics in Aging) was a prospective multicenter randomized open-label blinded Endpoint (PROBE) trial including 527 patients at risk for developing HF randomly assigned to either spironolactone (25-50mg/day) or usual care alone for a maximum of 9 months. Sitting BP was assessed at baseline, month 1 and 9 (or last visit). Analysis of covariance (ANCOVA), mixed effects models, and structural modelling equations were used.
Results
The median (percentile25-75) age was 73 (69-79) years, 26% were female, and >75% had history of hypertension. Overall, the baseline BP was 142/78 mmHg. Patients with higher BP were older, more likely to have diabetes and less likely to have coronary artery disease, had greater left ventricular mass (LVM), and left atrial volume (LAV). Compared with usual care, by last visit, spironolactone changed SBP by -10.3 (-13.0 to -7.5)mmHg and DBP by -3.2 (-4.8 to -1.7)mmHg (p < 0.001 for both). A higher proportion of patients on spironolactone had controlled BP < 130/80 mmHg (36 vs. 26%; p = 0.014). Lower baseline renin levels predicted a greater response to spironolactone (interactionp=0.041).
Conclusion
Spironolactone had a clinically important BP-lowering effect. Spironolactone should be considered for lowering blood pressure in patients who are at risk of developing HF.

© Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2021. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 01 Apr 2021; epub ahead of print
Ferreira JP, Collier T, Clark AL, Mamas MA, ... Cleland JG, Zannad F
Eur Heart J Cardiovasc Pharmacother: 01 Apr 2021; epub ahead of print | PMID: 33822033
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Impact:
Abstract

β-blocker and 1-year outcomes among patients hospitalized for heart failure with mid-range ejection fraction.

Wang B, Zhang L, Hu S, Bai X, ... Li J, Zheng X
Aims
The beneficial effect of β-blocker on heart failure with reduced ejection fraction (HFrEF) is well established. However, its effect on the 1-year outcome of heart failure with mid-range ejection fraction (HFmrEF) remains unclear.
Methods and results
We analysed the data of the patients with left ventricular ejection fraction (LVEF) between 40%-49% in China Patient-centred Evaluative Assessment of Cardiac Events Prospective Heart Failure Study (China PEACE 5p-HF Study), in which patients hospitalized for heart failure (HF) from 52 Chinese hospitals were recruited from 2016 to 2018. Two primary outcomes were all-cause death and all-cause hospitalization. The associations between β-blocker use at discharge and outcomes were assessed by inverse probability of treatment weighting (IPTW)-weighted Cox regression analyses. To assess consistency, IPTW adjusting medications analyses, multivariable analyses and dose-effect analyses were performed. 1035 HFmrEF patients were included in the analysis. The mean age was 65.5 ±12.7 years and 377 (36.4%) were female. The median (interquartile range) of LVEF was 44% (42%-47%). 661 (63.8%) were treated with β-blocker. Patients using β-blocker were younger with better cardiac function, and more likely to use renin-angiotensin system inhibitor and mineralocorticoid receptor antagonist. During the 1-year follow up, death occurred in 84 (12.7%) treated and 85 (22.7%) untreated patients (P < 0.0001); all-cause hospitalization occurred in 298 (45.1%) treated and 188 (50.3%) untreated patients (P = 0.04). After IPTW-weighted adjustment, β-blocker use was significantly associated with lower risk of all-cause death [hazard ratio (HR): 0.70; confidence interval (95% CI): 0.51-0.96, P = 0.03], but not with lower all-cause hospitalization (HR, 0.92, 95% CI, 0.76-1.10, P = 0.36). Consistency analyses showed consistent favourable effect of β-blocker on all-cause death, but not on all-cause hospitalization.
Conclusions
Among patients with HFmrEF, β-blocker use was associated with lower risk of all-cause death, but not with lower risk of all-cause hospitalization.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J Cardiovasc Pharmacother: 26 Mar 2021; epub ahead of print
Wang B, Zhang L, Hu S, Bai X, ... Li J, Zheng X
Eur Heart J Cardiovasc Pharmacother: 26 Mar 2021; epub ahead of print | PMID: 33774652
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Impact:
Abstract

Efficacy and safety of direct oral anticoagulant in morbidly obese patients with atrial fibrillation: systematic review and meta-analysis.

Thangjui S, Kewcharoen J, Yodsuwan R, Trongtorsak A, ... Winans ARM, Bischof E
Aims
We conducted a systematic review and meta-analysis on 3 outcomes. We assessed the efficacy and safety of direct oral anticoagulants (DOAC) compared to vitamin K antagonists (VKA) in morbidly obese patients with atrial fibrillation (AF). We compared the efficacy and safety of DOAC in obese patients and non-obese patients with AF. Finally, we updated the current knowledge of outcomes of AF patients with obesity compared to normal-weight patients regardless of anticoagulation type.
Methods and results
Using PubMed and Embase, we searched for literature published from inception to August 2020 for studies conducted in morbidly obese patients with AF who used DOACs and/or VKA for stroke or systemic embolism (stroke/SE) prevention that report efficacy and/or safety data. GRADE assessment was performed to determine the quality of the meta-analysis results. DOAC was not statistically different from VKA in reducing stroke/SE with RR of 0.85 (95%CI: 0.56 to 1.29; very low certainty evidence). Major bleeding risk was lower in the DOAC groups with RR of 0.62 (95%CI: 0.48 to 0.80; low certainty evidence). Obese patients with AF who used DOACs had lower risk of stroke/SE and similar major bleeding risk compared to nonobese patients with RR of 0.77 (95%CI: 0.70 to 0.84; low certainty evidence) and 1.02 (95%CI: 0.94 to 1.09; low certainty evidence), respectively. Obese patients with AF who used any type of anticoagulant had lower risk of stroke/SE compared to normal-weight patients with RR of 0.62 (95%CI: 0.57 to 0.69; low certainty evidence).
Conclusions
The use of DOACs in morbidly obese patients maybe reasonable if needed, but more dedicated studies are needed to make a more robust recommendation.

© Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2021. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 16 Mar 2021; epub ahead of print
Thangjui S, Kewcharoen J, Yodsuwan R, Trongtorsak A, ... Winans ARM, Bischof E
Eur Heart J Cardiovasc Pharmacother: 16 Mar 2021; epub ahead of print | PMID: 33730164
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Impact:
Abstract

Treatment of fabry disease with migalastat-outcome from a prospective 24 months observational multicenter study (FAMOUS).

Lenders M, Nordbeck P, Kurschat C, Eveslage M, ... Canaan-Kühl S, Brand E
Aims
Fabry disease (FD) is an X-linked lysosomal storage disorder caused by a deficiency of the lysosomal enzyme α-galactosidase A (GLA/AGAL) resulting in lysosomal accumulation of globotriaosylceramide (Gb3). Patients with amenable GLA mutations can be treated with migalastat, an oral pharmacologic chaperone increasing endogenous AGAL activity. In this prospective observational multicenter study safety as well as cardiovascular, renal, and patient-reported outcomes and disease biomarkers were assessed after 12 and 24 months of migalastat treatment under \"real world\" conditions.
Methods and results
54 patients (26 females) (33 of these [61.1%] pre-treated with enzyme replacement therapy) with amenable mutations were analyzed. Treatment was generally safe and well tolerated. 153 events per 1,000 patient-years were detected. Overall left ventricular mass index decreased after 24 months (all: -7.5 ± 17.4 g/m2, p = 0.0118; females: -4.6 ± 9.1 g/m2, p = 0.0554; males: -9.9 ± 22.2 g/m2, p = 0.0699). After 24 months, females and males presented with a moderate yearly loss of eGFR (-2.6 and -4.4 ml/min/1.73 m2 per year; p = 0.0317 and p = 0.0028, respectively). FD-specific manifestations/symptoms remained stable (all p > 0.05). 76.9% of females and 50% of males suffered from pain, which has not improved under treatment. FD-specific disease scores (DS3 and MSSI) remained stable during treatment. AGAL activities and plasma lyso-Gb3 values remained stable, although some male patients presented with increasing lyso-Gb3 levels over time.
Conclusions
Treatment with migalastat was generally safe and resulted in most patients in an amelioration of left ventricular mass. However, due to the heterogeneity of FD phenotypes, it is advisable that the treating physician monitors the clinical response regularly.

© Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2021. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 15 Mar 2021; epub ahead of print
Lenders M, Nordbeck P, Kurschat C, Eveslage M, ... Canaan-Kühl S, Brand E
Eur Heart J Cardiovasc Pharmacother: 15 Mar 2021; epub ahead of print | PMID: 33725118
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Impact:
Abstract

Antithrombotic therapy in patients with acute coronary syndrome complicated by cardiogenic shock or out-of-hospital cardiac arrest: a joint position paper from the European Society of Cardiology (ESC) Working Group on Thrombosis, in association with the Acute Cardiovascular Care Association (ACCA) and European Association of Percutaneous Cardiovascular Interventions (EAPCI).

Gorog DA, Price S, Sibbing D, Baumbach A, ... Vranckx P, Rocca B
Timely and effective antithrombotic therapy is critical to improving outcome, including survival, in patients with acute coronary syndrome (ACS). Achieving effective platelet inhibition and anticoagulation, with minimal risk, is particularly important in high-risk ACS patients, especially those with cardiogenic shock (CS) or those successfully resuscitated following out-of-hospital cardiac arrest (OHCA), who have a 30-50% risk of death or a recurrent ischaemic event over the subsequent 30 days. There are unique challenges to achieving effective and safe antithrombotic treatment in this cohort of patients that are not encountered in most other ACS patients. This position paper focuses on patients presenting with CS or immediately post-OHCA, of presumed ischaemic aetiology, and examines issues related to thrombosis and bleeding risk. Both the physical and pharmacological impacts of CS, namely impaired drug absorption, metabolism, altered distribution and/or excretion, associated multiorgan failure, co-morbidities and co-administered treatments such as opiates, targeted temperature management, renal replacement therapy and circulatory or left ventricular assist devices, can have major impact on the effectiveness and safety of antithrombotic drugs. Careful attention to the choice of antithrombotic agent(s), route of administration, drug-drug interactions, therapeutic drug monitoring and factors that affect drug efficacy and safety, may reduce the risk of sub- or supra-therapeutic dosing and associated adverse events. This paper provides expert opinion, based on best available evidence, and consensus statements on optimising antithrombotic therapy in these very high-risk patients, in whom minimising the risk of thrombosis and bleeding is critical to improving outcome.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 14 Mar 2021; 7:125-140
Gorog DA, Price S, Sibbing D, Baumbach A, ... Vranckx P, Rocca B
Eur Heart J Cardiovasc Pharmacother: 14 Mar 2021; 7:125-140 | PMID: 32049278
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Impact:
Abstract

Very short vs. long dual antiplatelet therapy after second generation drug-eluting stents in 35 785 patients undergoing percutaneous coronary interventions: a meta-analysis of randomized controlled trials.

Benenati S, Galli M, Marzo V, Pescetelli F, ... Crea F, Porto I
Aim
To provide an updated assessment of the efficacy-safety profile of very short (1 or 3 months) dual antiplatelet therapy (DAPT) compared with long (12 months) DAPT in patients undergoing percutaneous coronary interventions (PCIs).
Methods and results
Seven randomized controlled trials (RCTs) comparing very short vs. long DAPT in 35 785 patients undergoing PCI were selected. The primary efficacy endpoint was major adverse cardiovascular events (MACE) and the primary safety endpoint trial-defined major bleeding through at least 1 year. Compared with longer duration, very short DAPT yielded comparable rates of MACE [odds ratio (OR) 0.93, 95% confidence interval (CI) 0.84-1.03, P = 0.19], all-cause mortality (OR 0.92, 95% CI 0.80-1.06, P = 0.25), myocardial infarction (OR 1.01, 95% CI 0.88-1.15, P = 0.91), stroke (OR 1.04, 95% CI 0.72-1.50, P = 0.83), stent thrombosis (OR 1.05, 95% CI 0.80-1.37, P = 0.73), target vessel revascularization (OR 0.99, 95% CI 0.82-1.18, P = 0.89), and comparable net clinical benefit (OR 0.92, 95% CI 0.84-1.01, P = 0.08). Very short DAPT was associated with reduced rates of major bleeding (OR 0.61, 95% CI 0.40-0.94, P = 0.03) or any bleeding (OR 0.65, 95% CI 0.47-0.90, P = 0.009). Subgroup analyses showed consistent results for 1 vs. 3 month DAPT and for aspirin vs. P2Y12 inhibitor monotherapy following very short DAPT.
Conclusions
Compared with long DAPT, very short DAPT did not increase the odds of ischaemic complications, while reducing the odds of major or any bleeding by over 30%.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 14 Mar 2021; 7:86-93
Benenati S, Galli M, Marzo V, Pescetelli F, ... Crea F, Porto I
Eur Heart J Cardiovasc Pharmacother: 14 Mar 2021; 7:86-93 | PMID: 31942965
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Impact:
Abstract

Glucagon-like peptide-1 receptor agonists and the risk of cardiovascular events in diabetes patients surviving an acute myocardial infarction.

Trevisan M, Fu EL, Szummer K, Norhammar A, ... Jernberg T, Carrero JJ
Aims
Trial evidence indicates that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may reduce the risk of cardiovascular (CV) events in patients with diabetes and myocardial infarction (MI). We aimed to expand this observation to routine care settings.
Methods and results
Prospective observational study including all patients with diabetes surviving an MI and registered in the nationwide SWEDEHEART registry during 2010-17. Multivariable Cox regression analyses were used to estimate the association between GLP-1 RAs use and the study outcome, which was a composite of stroke, heart failure, Re-infarction, or CV death. Covariates included demographics, comorbidities, presentation at admission, and use of secondary CV prevention therapies. In total, 17 868 patients with diabetes were discharged alive after a first event of MI. Their median age was 71 years, 36% were women and their median estimated glomerular filtration rate was 75 mL/min/1.73m2. Of those, 365 (2%) were using GLP-1 RAs. During median 3 years of follow-up, 7005 patients experienced the primary composite outcome. Compared with standard of diabetes care, use of GLP-1 RAs was associated with a lower event risk [adjusted hazard ratio (HR) 0.72; 95% confidence interval (CI): 0.56-0.92], mainly attributed to a lower rate of re-infarction and stroke. Results were similar after propensity score matching or when compared with users of sulfonylurea. There was no suggestion of heterogeneity across subgroups of age, sex, chronic kidney disease, and STEMI.
Conclusion
GLP-1 RAs use, compared with standard of diabetes care, was associated with lower risk for major CV events in healthcare-managed survivors of an MI.

© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J Cardiovasc Pharmacother: 14 Mar 2021; 7:104-111
Trevisan M, Fu EL, Szummer K, Norhammar A, ... Jernberg T, Carrero JJ
Eur Heart J Cardiovasc Pharmacother: 14 Mar 2021; 7:104-111 | PMID: 31999317
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Impact:
Abstract

Comparison of P2Y12 receptor inhibitors in patients with ST-elevation myocardial infarction in clinical practice: a propensity score analysis of five contemporary European registries.

De Luca L, Zeymer U, Claeys MJ, Dörler J, ... Jukema JW, PIRAEUS group
Aims
Among acute coronary syndromes (ACS), ST-segment elevation myocardial infarction (STEMI) has the most severe early clinical course. Recent randomized clinical trials have demonstrated that novel antithrombotic therapies improve in-hospital outcomes in STEMI patients. We aimed to describe the effectiveness and safety of P2Y12 receptor inhibitors in clinical practice in patients with STEMI based on data from contemporary European ACS registries.
Methods and results
Five registries from the PIRAEUS initiative (AAPCI/ADPAT, ALKK-PIC, AMIS Plus, Belgium STEMI, and EYESHOT) provided data for the assessment of P2Y12 receptor inhibitor-based dual antiplatelet therapy. Registries were heterogeneous in terms of setting, patient characteristics, and treatment selection. Matched pair analysis and propensity score matching were used to assess all-cause in-hospital death rates based on data from 25 250 patients (8577 patients on prasugrel, 5995 on ticagrelor, and 10 678 on clopidogrel). The odds ratio (OR) for the death of any cause when compared with clopidogrel was 0.72 [95% confidence interval (CI) 0.62-0.84, P < 0.001] in favour of the new P2Y12 receptor inhibitors (prasugrel and ticagrelor combined). In the comparison between prasugrel and ticagrelor, there were no relevant differences (OR 0.97, 95% CI 0.77-1.23; P = 0.81). Event rates of cardiovascular death and stroke were also substantially lower for the new P2Y12 receptor inhibitors. The differences between clopidogrel and prasugrel or ticagrelor on major bleeding were numerically in the same order as for death of any cause but were not statistically significant. No differences in ischaemic and bleeding outcomes were observed between prasugrel and ticagrelor.
Conclusion
This analysis suggests that the prasugrel or ticagrelor compared with clopidogrel have favourable outcomes in clinical practice while not being inferior in terms of safety.

© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J Cardiovasc Pharmacother: 14 Mar 2021; 7:94-103
De Luca L, Zeymer U, Claeys MJ, Dörler J, ... Jukema JW, PIRAEUS group
Eur Heart J Cardiovasc Pharmacother: 14 Mar 2021; 7:94-103 | PMID: 31965164
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Impact:
Abstract

Practical guidance for P2Y12 inhibitors in acute myocardial infarction undergoing percutaneous coronary intervention.

Lee SH, Kim HK, Jeong MH, Yasuda S, ... JAMIR, and SMART-DATE Investigators
Aims
Potent P2Y12 inhibitors for dual antiplatelet therapy (DAPT) is crucial for managing acute myocardial infarction; however, the selection of drugs is based on limited clinical information such as age and body weight. The current study sought to develop and validate a new risk scoring system that can be used to guide the selection of potent P2Y12 inhibitors by balancing ischaemic benefit and bleeding risk.
Methods and results
Derivation cohort of 10 687 patients who participated in the Korea Acute Myocardial Infarction Registry-National Institutes of Health study was used to construct a new scoring system. We combined the ischaemic and bleeding models to establish a simple clinical prediction score. Among the low score group (n = 1764), the observed bleeding risk (8.7% vs. 4.4%, P < 0.001) due to potent P2Y12 inhibitors exceeded ischaemic benefit (1.3% vs. 2.2%, P = 0.185) during 12 months. Conversely, the high score group (n = 1898) showed an overall benefit from taking potent P2Y12 inhibitors from the standpoint of observed ischaemic (17.1% vs. 8.6%, P < 0.001) and bleeding events (10.1% vs. 6.8%, P = 0.073). The performance of ischaemic [integrated area under the curve (iAUC) = 0.809] and bleeding model (iAUC = 0.655) was deemed to be acceptable.
Conclusion
The new scoring system is a useful clinical tool for guiding DAPT by balancing ischaemic benefit and bleeding risk, especially among Asian populations. Further validation studies with other cohorts will be required to verify that the new system meets the needs of real clinical practice.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 14 Mar 2021; 7:112-124
Lee SH, Kim HK, Jeong MH, Yasuda S, ... JAMIR, and SMART-DATE Investigators
Eur Heart J Cardiovasc Pharmacother: 14 Mar 2021; 7:112-124 | PMID: 31977008
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Impact:
Abstract

Low adherence to statin treatment during the 1st year after an acute myocardial infarction is associated with increased 2nd-year mortality risk-an inverse probability of treatment weighted study on 54 872 patients.

Khalaf K, Johnell K, Austin PC, Tyden P, ... Perez-Vicente R, Merlo J
Aims
Experiencing an acute myocardial infarction (AMI) is a life-threatening event and use of statins can reduce the probability of recurrence and improve long-term survival. However, the effectiveness of statins in the real-world setting may be lower than the reported efficacy in randomized clinical trials. Therefore, we aimed to investigate whether low statin treatment adherence during the year following an AMI episode is associated with increased 2nd-year mortality.
Methods and results
We analysed all 54 872 AMI patients aged ≥45 years, admitted to Swedish hospitals between 2010 and 2012, and who survive at least 1 year after the AMI episode. We defined low adherence as a medication possession ratio <50% or non-use of statins. Applying inverse probability of treatment weighting (IPTW), we investigated the association between low adherence and all-cause, cardiovascular disease (CVD), and non-CVD mortality during the 2nd year. Overall, 20% of the patients had low adherence during the 1st year and 8% died during the 2nd year. In the IPTW analysis, low adherence was associated with an increased risk of all-cause [absolute risk difference (ARD) = 0.048, number needed to harm (NNH) = 21, relative risk (RR) = 1.71], CVD (ARD = 0.035, NNH = 29, RR = 1.62), and non-CVD mortality (ARD = 0.013, NNH = 77, RR = 2.17).
Conclusion
In the real-world setting, low statin adherence during the 1st year after an AMI episode is associated with increased mortality during the 2nd year. Our results reaffirm the importance of achieving a high adherence to statin treatment after suffering from an AMI.

© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J Cardiovasc Pharmacother: 14 Mar 2021; 7:141-147
Khalaf K, Johnell K, Austin PC, Tyden P, ... Perez-Vicente R, Merlo J
Eur Heart J Cardiovasc Pharmacother: 14 Mar 2021; 7:141-147 | PMID: 32058542
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Impact:
Abstract

A systematic review and meta-analysis to evaluate the clinical outcomes in COVID-19 patients on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers.

Grover A, Oberoi M
Introduction
Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) share their target receptor site with the SARS-CoV-2 virus, that may cause ACE2 receptor up-regulation which raised concerns regarding ACEI and ARB use in COVID-19 patients. However, many medical professional societies recommended their continued use given the paucity of clinical evidence, but there is a need for an updated systematic review and meta-analysis of the latest clinical studies.
Methods and results
A search was conducted on PubMed, Google Scholar, EMBASE, and various preprint servers for studies comparing clinical outcomes and mortality in COVID-19 patients on ACEIs and/or ARBs, and a meta-analysis was performed. A total of 16 studies were included for the review and meta-analysis. There were conflicting findings reported in the rates of severity and mortality in several studies. In a pooled analysis of four studies, there was a statistically non-significant association of ACEI/ARB use with lower odds of developing severe disease vs. non-users [odds ratio (OR) = 0.81, 95% confidence interval (CI): 0.41-1.58, I2=50.52, P-value = 0.53). In a pooled analysis of six studies, there was a statistically non-significant association of ACEI/ARB use with lower odds of mortality as compared with non-users (OR = 0.86, 95% CI = 0.53-1.41, I2 = 79.12, P-value = 0.55).
Conclusion
It is concluded that ACEIs and ARBs should be continued in COVID-19 patients, reinforcing the recommendations made by several medical societies. Additionally, the individual patient factors such as ACE2 polymorphisms which might confer higher risk of adverse outcomes need to be evaluated further.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 14 Mar 2021; 7:148-157
Grover A, Oberoi M
Eur Heart J Cardiovasc Pharmacother: 14 Mar 2021; 7:148-157 | PMID: 32542337
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Impact:
Abstract

Left ventricular thrombosis: new perspectives on an old problem.

Massussi M, Scotti A, Lip GYH, Proietti R
Left ventricular thrombosis (LVT) is a major risk factor for systemic thromboembolism and might complicate both the acute and the chronic phase of ischaemic heart disease after myocardial infarction and, less frequently, non-ischaemic cardiomyopathies. The pathophysiology of thrombus formation is complex and involves the three aspects of Virchow\'s triad: blood stasis, prothrombotic state, and tissue injury. Advances in technology have improved the detection rate of intracardiac thrombi, but several uncertainties still remain regarding the optimal treatment strategy within daily clinical practice. Of note, anticoagulation therapy with heparin and vitamin K antagonists decreases the risk of embolic stroke though exposing patients to an undeniable risk of bleeding complications. Although limited data on the off-label use of direct oral anticoagulants have reported safety and efficacy for LVT resolution, yet more evidence is needed to justify their use in clinical practice.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 14 Mar 2021; 7:158-167
Massussi M, Scotti A, Lip GYH, Proietti R
Eur Heart J Cardiovasc Pharmacother: 14 Mar 2021; 7:158-167 | PMID: 32569361
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Impact:
Abstract

The Role of Pharmacogenomics in Contemporary Cardiovascular Therapy: A position statement from the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy.

Magavern EF, Kaski JC, Turner RM, Drexel H, ... Pirmohamed M, Caulfield MJ
There is a strong and ever-growing body of evidence regarding the use of pharmacogenomics to inform cardiovascular pharmacology. However, there is no common position taken by international cardiovascular societies to unite diverse availability, interpretation and application of such data, nor is there recognition of the challenges of variation in clinical practice between countries within Europe. Aside from the considerable barriers to implementing pharmacogenomic testing and the complexities of clinically actioning results, there are differences in the availability of resources and expertise internationally within Europe. Diverse legal and ethical approaches to genomic testing and clinical therapeutic application also require serious thought. As direct-to-consumer genomic testing becomes more common, it can be anticipated that data may be brought in by patients themselves, which will require critical assessment by the clinical cardiovascular prescriber. In a modern, pluralistic and multi-ethnic Europe, self-identified race/ethnicity may not be concordant with genetically detected ancestry and thus may not accurately convey polymorphism prevalence. Given the broad relevance of pharmacogenomics to areas such as thrombosis and coagulation, interventional cardiology, heart failure, arrhythmias, clinical trials, and policy/regulatory activity within cardiovascular medicine, as well as to genomic and pharmacology subspecialists, this position statement attempts to address these issues at a wide-ranging level.

© Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2021. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 25 Feb 2021; epub ahead of print
Magavern EF, Kaski JC, Turner RM, Drexel H, ... Pirmohamed M, Caulfield MJ
Eur Heart J Cardiovasc Pharmacother: 25 Feb 2021; epub ahead of print | PMID: 33638977
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Impact:
Abstract

Cardiac and Cardiometabolic Phenotyping of Trastuzumab-Mediated Cardiotoxicity: a Secondary Analysis of the MANTICORE trial.

Kirkham AA, Pituskin E, Thompson RB, Mackey JR, ... Oudit GY, Paterson DI
Aims
An improved understanding of the pathophysiology of trastuzumab-mediated cardiotoxicity is required to improve outcomes of patients with HER2-positive breast cancer. We aimed to characterize the cardiac and cardiometabolic phenotype of trastuzumab-mediated toxicity and potential interactions with cardiac pharmacotherapy.
Methods and results
This study was an analysis of serial magnetic resonance imaging (MRI) and circulating biomarker data acquired from patients with HER2-positive early stage breast cancer participating in a randomized-controlled clinical trial for the pharmaco-prevention of trastuzumab-associated cardiotoxicity. Circulating biomarkers (B-type natriuretic peptide, troponin I, MMP-2 and -9, GDF-15, neuregulin-1 and IGF-1) and MRI of cardiac structure and function and abdominal fat distribution were acquired prior to trastuzumab, post-cycle 4 and post-cycle 17. Ninety-four participants (51±8 years) completed the study with 30 on placebo, 33 on perindopril, and 31 on bisoprolol. Post-cycle 4, global longitudinal strain (GLS) deteriorated from baseline in both placebo (+2.0±2.7%, p = 0.002) and perindopril (+0.9±2.5%, p = 0.04), but not with bisoprolol (-0.2±2.1%, p = 0.55). In all groups combined, extracellular volume fraction and GDF-15 increased post-cycle 4 (+1.3±4.4%, p = 0.004; +130±150%, p ≤ 0.001, respectively). However, no significant change in troponin I was detected throughout trastuzumab. In all groups combined, visceral and intermuscular fat volume increased post-cycle 4 (+7±17%, p = 0.02, +8±23%, p = 0.02, respectively), while muscle volume and IGF-1 decreased from post-cycle 4 to 17 (-2±10%, p = 0.008, -18±28%, p < 0.001, respectively).
Conclusion
Trastuzumab results in impaired cardiac function and early myocardial inflammation. Trastuzumab is also associated with deleterious changes to the cardiometabolic phenotype which may contribute to the increased cardiovascular risk in this population.

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Eur Heart J Cardiovasc Pharmacother: 18 Feb 2021; epub ahead of print
Kirkham AA, Pituskin E, Thompson RB, Mackey JR, ... Oudit GY, Paterson DI
Eur Heart J Cardiovasc Pharmacother: 18 Feb 2021; epub ahead of print | PMID: 33605416
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Impact:
Abstract

Epinephrine administration for adult out-of-hospital cardiac arrest patients with refractory shockable rhythm: time-dependent propensity score-sequential matching analysis from a nationwide population-based registry.

Matsuyama T, Komukai S, Izawa J, Gibo K, ... Ohta B, Kitamura T
Background
Little is known about the effect of prehospital epinephrine administration in out-of-hospital cardiac arrest (OHCA) patients with refractory shockable rhythm, for whom initial defibrillation was unsuccessful.
Methods
This study using Japanese nationwide population-based registry included all adult OHCA patients aged ≥18 years with refractory shockable rhythm between January 2014 and December 2017. Patients with or without epinephrine during cardiac arrest were sequentially matched using a risk set matching based on the time-dependent propensity scores within the same minute. The primary outcome was 1-month survival. The secondary outcomes included 1-month survival with favourable neurological outcome (cerebral performance category scale: 1 or 2) and prehospital return of spontaneous circulation (ROSC).
Results
Of the 499,944 patients registered in the database during the study period, 22,877 were included. Among them, 8,467 (37.0%) received epinephrine. After time-dependent propensity score-sequential matching, 16,798 patients were included in the matched cohort. In the matched cohort, positive associations were observed between epinephrine and 1-month survival (epinephrine: 17.3% [1,454/8,399] vs. no epinephrine: 14.6% [1,224/8,399]; RR 1.22 [95% confidence interval {CI}, 1.13-1.32]) and prehospital ROSC (epinephrine: 22.2% [1,868/8,399] vs. no epinephrine: 10.7% [900/8399]; RR, 2.07 [95% CI, 1.91-2.25]). No significant positive association was observed between epinephrine and favourable neurological outcome (epinephrine: 7.8% [654/8,399] vs. no epinephrine: 7.1% [611/8,399]; RR, 1.13 [95% CI, 0.998-1.27]).
Conclusions
Using the nationwide population-based registry with time-dependent propensity score-sequential matching analysis, prehospital epinephrine administration in adult OHCA patients with refractory shockable rhythm was positively associated with 1-month survival and prehospital ROSC.

© Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2021. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 17 Feb 2021; epub ahead of print
Matsuyama T, Komukai S, Izawa J, Gibo K, ... Ohta B, Kitamura T
Eur Heart J Cardiovasc Pharmacother: 17 Feb 2021; epub ahead of print | PMID: 33599265
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Impact:
Abstract

Recombinant human Lecithin-Cholesterol acyltransferase in patients with atherosclerosis: Phase 2a primary results and phase 2b design.

Bonaca MP, George RT, Morrow DA, Bergmark BA, ... Hsia J, Sabatine MS
Background
Reverse cholesterol transport (RCT) removes cholesterol and stabilizes vulnerable plaques. In addition, high-density lipoprotein (HDL) may be cardioprotective in acute MI. Lecithin-cholesterol acyltransferase (LCAT) may enhance RCT. The objective of this study was to investigate the pharmacokinetics, pharmacodynamics, and safety of multiple ascending doses of recombinant human LCAT (MEDI6012) to inform a Phase 2 b program.
Methods
This was a randomized, blinded, placebo-controlled, dose-escalation Phase 2a study of MEDI6012. Patients were randomized into 1 of 4 cohorts (40, 120, 300 mg IV weekly x3 doses, or 300 mg IV-push, 150 mg at 48-hours and 100 mg at 7 days). All cohorts were planned to randomize 6:2 (MEDI6012 vs placebo). The primary endpoints were baseline-adjusted AUC from 0-96 hours post dose-3 (AUC0-96hr) for HDL-C, HDL cholesteryl ester (HDL-CE), and total cholesteryl ester (CE). The primary safety endpoints were treatment-emergent adverse events (AEs).
Results
A total of 32 patients were randomized. MEDI6012 significantly increased AUC0-96hr for HDL-C, HDL-CE and CE in a graded fashion with increasing doses. Relative to placebo, MEDI6012 increased HDL-C at Day 19 by 66% (95%CI 33-99, p = 0.014) with 120 mg and 144% (95%CI 108-181, p < 0.001) with 300 mg. An IV-push increased HDL-C by 40.8% at 30 minutes. Overall AEs were similar between groups with no severe, life-threatening/fatal AEs or neutralizing antibodies.
Conclusions
Multiple ascending doses of MEDI6012 were safe and well tolerated and significantly increased HDL-C, HDL-CE and CE in a dose-related manner. These data support the ongoing Phase 2 b program investigating MEDI6012 in ST-elevation MI.

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Eur Heart J Cardiovasc Pharmacother: 24 Jan 2021; epub ahead of print
Bonaca MP, George RT, Morrow DA, Bergmark BA, ... Hsia J, Sabatine MS
Eur Heart J Cardiovasc Pharmacother: 24 Jan 2021; epub ahead of print | PMID: 33493256
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Impact:
Abstract

Off-label underdosed apixaban use in Asian patients with non-valvular atrial fibrillation.

Lee SR, Choi EK, Park SH, Jung JH, ... Oh S, Lip GYH
Aims
To compare the effectiveness and safety of off-label underdosed apixaban with on-label standard dose apixaban in Asian patients with atrial fibrillation (AF).
Methods and results
Using the Korean nationwide claims database, we identified patients who were prescribed apixaban and did not fulfil the dose reduction criteria for apixaban between January 2015 and December 2017. A multivariable Cox hazard regression model was performed, and hazard ratios (HRs) for ischemic stroke, major bleeding (MB), all-cause death, and composite outcome were analysed. Compared to patients prescribed on-label standard dose apixaban (n = 4,194), patients prescribed off-label underdosed apixaban (n = 2,890) showed a higher risk of ischemic stroke (adjusted HR [aHR], 1.38; 95% confidence interval [CI], 1.06-1.81), all-cause death (aHR, 1.19; 95% CI, 1.01-1.39), and the composite outcome (aHR, 1.17; 95% CI, 1.03-1.34), but with no significant differences in MB between the two groups. Among the patients who did not meet any dose reduction criteria, off-label underdosed apixaban use was associated with a significantly higher risk of ischemic stroke than on-label standard dose apixaban use (aHR, 1.85; 95% CI, 1.25-2.73). Among the patients who met a single dose reduction criterion, off-label underdosed apixaban use was associated with a higher risk of all-cause death than on-label standard dose apixaban (aHR, 1.32; 95% CI, 1.07-1.64).
Conclusion
The off-label underdosed apixaban group showed higher risks of ischemic stroke, all-cause death, and composite clinical outcomes than the on-label standard dose apixaban group, but both showed comparable risks of MB. Label-adherence to apixaban dosing should be emphasised to achieve the best clinical outcomes for Asian patients with AF.

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Eur Heart J Cardiovasc Pharmacother: 19 Jan 2021; epub ahead of print
Lee SR, Choi EK, Park SH, Jung JH, ... Oh S, Lip GYH
Eur Heart J Cardiovasc Pharmacother: 19 Jan 2021; epub ahead of print | PMID: 33471125
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Impact:
Abstract

THE CARDIOVASCULAR EFFECTS OF GNRH ANTAGONISTS IN MEN WITH PROSTATE CANCER.

Cirne F, Aghel N, Petropoulos JA, Klotz L, ... Pinthus J, Leong DP
Aims
The aim of this study was to determine whether gonadotropin-releasing hormone (GnRH) antagonists (an emerging class of drugs to suppress testosterone synthesis in the treatment of prostate cancer) cause less adverse cardiovascular events than the more commonly use GnRH agonists.
Methods and results
We conducted a systematic review to identify all randomised, controlled trials in which a GnRH antagonist was compared with a GnRH agonist in men with prostate cancer. We identified ten eligible studies including two different GnRH antagonists, degarelix (n = 1681) and relugolix (n = 734), which were compared with the GnRH agonists, leuprolide (n = 714) and goserelin (n = 600). The pooled risk ratios (95% confidence intervals) among GnRH antagonist recipients for adverse cardiovascular events, cardiovascular death and all-cause mortality were 0.57 (0.39-0.81); 0.49 (0.25-0.96); and 0.48 (0.28-0.83) respectively. Important limitations of the included trials were their short duration of follow-up, unblinded study design and (in most of the studies) the identification of adverse cardiovascular events through safety reporting mechanisms rather than as a pre-specified outcome. There was no evidence of heterogeneity of findings among the studies.
Conclusions
There is consistent but methodologically limited data to suggest that GnRH antagonists - a relatively new class of androgen deprivation therapy for prostate cancer - cause significantly less cardiovascular adverse effects than the more frequently used GnRH agonists.

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Eur Heart J Cardiovasc Pharmacother: 19 Jan 2021; epub ahead of print
Cirne F, Aghel N, Petropoulos JA, Klotz L, ... Pinthus J, Leong DP
Eur Heart J Cardiovasc Pharmacother: 19 Jan 2021; epub ahead of print | PMID: 33470403
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Impact:
Abstract

Obesity and atrial fibrillation: making inroads through fat.

Javed S, Gupta D, Lip GYH
The global prevalence of obesity has reached epidemic proportions, paralleled by a rise in cases of atrial fibrillation (AF). Data from epidemiological cohorts support the role of obesity as an independent risk factor for AF. Increasing evidence indicates that obesity may contribute to the AF substrate through a number of pathways including by altering epicardial adipose tissue biology, inflammatory pathways, structural cardiac remodelling, and inducing atrial fibrosis. Due to changes in pharmacokinetics and pharmacodynamics, specific therapeutic considerations are required to guide management of patients with AF including anticoagulation and rhythm control. Also, weight loss in patients with AF has been associated with reduced progression from paroxysmal to persistent AF and indeed regression from persistent to proximal AF. However, the role of dietary intervention in AF control remains to be fully elucidated and hard prospective outcome data to support weight loss are required in AF to determine its role as part of a comprehensive risk factor management strategy for AF in obese patients.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 15 Jan 2021; 7:59-67
Javed S, Gupta D, Lip GYH
Eur Heart J Cardiovasc Pharmacother: 15 Jan 2021; 7:59-67 | PMID: 32096865
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Impact:
Abstract

Choices in antithrombotic management for patients with atrial fibrillation undergoing percutaneous coronary intervention: questions (and answers) in chronological sequence.

Rubboli A, Valgimigli M, Capodanno D, Lip GYH
In accordance with the 2018 joint consensus document issued by the European Heart Rhythm Association (EHRA), European Society of Cardiology (ESC) Working Group on Thrombosis, European Association of Percutaneous Cardiovascular Interventions (EAPCI), and European Association of Acute Cardiac Care (ACCA), and endorsed by the Heart Rhythm Society (HRS), Asia-Pacific Heart Rhythm Society (APHRS), Latin America Heart Rhythm Society (LAHRS), and Cardiac Arrhythmia Society of Southern Africa (CASSA), as well as with other recent ESC Guidelines, the management of antithrombotic therapy of patients with atrial fibrillation undergoing percutaneous coronary intervention requires that multiple and interconnected issues, including, duration of initial triple antithrombotic therapy, selection of P2Y12 inhibitor, choice of oral anticoagulant to be combined with antiplatelet therapy, intensity of oral anticoagulation throughout combination therapy, and choice of oral anticoagulant for indefinite therapy, are addressed. To assist the responsible physician in clinical decision making, a series of practical questions are proposed and discussed in the chronological sequence they should likely be answered.

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Eur Heart J Cardiovasc Pharmacother: 15 Jan 2021; 7:68-73
Rubboli A, Valgimigli M, Capodanno D, Lip GYH
Eur Heart J Cardiovasc Pharmacother: 15 Jan 2021; 7:68-73 | PMID: 32379867
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Impact:
Abstract

Effects of intensive urate lowering therapy with febuxostat in comparison with allopurinol on pulse wave velocity in patients with gout and increased cardiovascular risk: the FORWARD study.

Desideri G, Rajzer M, Gerritsen M, Nurmohamed MT, ... Tausche AK, Borghi C
Aims
Hyperuricaemia and gout are strongly related with traditional cardiovascular risk factors and vascular damage. This study aimed to assess whether febuxostat and allopurinol could differently influence carotid-femoral pulse wave velocity (cfPWV) in patients with gout and elevated serum uric acid (SUA) levels.
Methods and results
A multi-centre, multinational, phase IV, randomized, parallel-group, active-controlled, open label trial with blind end-points evaluation. One hundred and ninetyseven adults with gout and SUA levels ≥8 mg/dL were randomised to febuxostat or allopurinol in a 1:1 ratio for 36 weeks. The primary outcome was the comparison of the effects of febuxostat and allopurinol on changes in cfPWV. The mean cfPWV values at randomisation and week 36 were respectively 8.69 m/s and 9.00 m/s for subjects randomised to febuxostat and 9.02 m/s and 9.05 m/s for subjects randomised to allopurinol. No statistically significant changes in cfPWV by treatment assignment were observed at any time point for any of the assessed parameters. More subjects who received febuxostat had serum urate concentrations ≤6 mg/dL following treatment (78.3% vs 61.1% at week 36, p = 0.0137). Treatment-emergent adverse events were reported by 51 (52.0%) patients randomised to febuxostat and 63 (62.5%) patients randomised to allopurinol. The majority of events were mild in both treatment groups and included gout flares and arthralgia.
Conclusions
In patients with gout and elevated SUA levels the arterial stiffness remained stable both with febuxostat and allopurinol. Febuxostat was more effective and faster than allopurinol in achieving the SUA target. Both treatments were safe and well tolerated.

© Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2021. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 06 Jan 2021; epub ahead of print
Desideri G, Rajzer M, Gerritsen M, Nurmohamed MT, ... Tausche AK, Borghi C
Eur Heart J Cardiovasc Pharmacother: 06 Jan 2021; epub ahead of print | PMID: 33410912
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Impact:
Abstract

Heterogeneity of diabetes as a risk factor for major adverse cardiovascular events in anticoagulated patients with atrial fibrillation: an analysis of the ARISTOTLE trial.

De Caterina R, Patti G, Westerbergh J, Horowitz J, ... Alexander JH, Wallentin L
Aims
Whether diabetes without insulin therapy is an independent cardiovascular (CV) risk factor in atrial fibrillation (AF) has recently been questioned. We investigated the prognostic relevance of diabetes with or without insulin treatment in patients in the ARISTOTLE trial.
Methods and results
Patients with AF and increased stroke risk randomized to apixaban vs. warfarin were classified according to diabetes status: no diabetes; diabetes on no diabetes medications; diabetes on non-insulin antidiabetic drugs only; or insulin-treated. The associations between such patient subgroups and stroke/systemic embolism (SE), myocardial infarction (MI), and CV death were examined by Cox proportional hazard regression, both unadjusted and adjusted for other prognostic variables. Patients with diabetes were younger and had a higher body mass index. Median CHA2DS2VASc score was 4.0 in patients with diabetes and 3.0 in patients without diabetes. We found no significant difference in stroke/SE incidence across patient subgroups. Compared with no diabetes, only insulin-treated diabetes was significantly associated with higher risk. When adjusted for clinical variables, compared with no diabetes, the hazard ratios (HRs) for MI (95% confidence intervals) were for diabetes on no medication: 1.15 (0.62-2.14); for diabetes on non-insulin antidiabetic drugs: 1.32 (0.90-1.94); for insulin-treated diabetes: 2.34 (1.43-3.82); interaction P = 0.008. HRs for CV death were for diabetes on no medication: 1.19 (0.86-166); for diabetes on non-insulin antidiabetic drugs: 1.12 (0.88-1.42); for insulin-treated diabetes 1.85 (1.36-2.53), interaction P = 0.001.
Conclusion
In anticoagulated patients with AF, a higher risk of MI and CV death is largely confined to diabetes treated with insulin.

© The Author(s) 2020. Published on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 27 Dec 2020; epub ahead of print
De Caterina R, Patti G, Westerbergh J, Horowitz J, ... Alexander JH, Wallentin L
Eur Heart J Cardiovasc Pharmacother: 27 Dec 2020; epub ahead of print | PMID: 33367487
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Impact:
Abstract

Renin-angiotensin system blockers, risk of SARS-CoV-2 infection and outcomes fromCoViD-19: systematic review and meta-analysis.

Lee MMY, Docherty KF, Sattar N, Mehta N, ... Jhund PS, McMurray JJV
Aims
This meta-analysis provides summary odds ratio (OR) estimates for associations between treatment with (vs. without) renin-angiotensin system (RAS) blockers and risk of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection and coronavirus disease 2019 (CoViD-19) severity (including case-fatality) in patients with hypertension, and in all patients (irrespective of hypertension).
Methods and results
PubMed, EMBASE, Web of Science, Google Scholar, medRxiv and SSRN were searched (May 02, 2020 to August 12, 2020) for non-randomised observational CoViD-19 studies. Event/patient numbers were extracted, comparing ACE inhibitor/ARB treatment (and each separately), to treatment with neither drug, for the outcomes: (a) Likelihood of SARS-CoV-2 infection; (b) CoViD-19 severity (including hospitalisation, Intensive Therapy Unit (ITU), ventilation); (c) Case-fatality. Risk of bias was assessed (ROBINS-I). Random-effects meta-analysis estimates were pooled. Eighty six studies including 459,755 patients (103,317 with hypertension), were analysed. In patients with hypertension, ACE inhibitor or ARB treatment was not associated with a greater likelihood of SARS-CoV-2 infection in 60,141 patients (OR 1.06, 95% CI 0.99-1.14), hospitalisation in 5,925 patients (OR 0.90, 0.62-1.31), ITU in 7,218 patients (OR 1.06, 0.73-1.56), ventilation (or ITU/ventilation/death) in 13,163 patients (OR 0.91, 0.72-1.15) or case-fatality in 18,735 patients with 2,893 deaths (OR 0.75, 0.61-0.92).
Conclusion
ACE inhibitors and ARBs appear safe in the context of SARS-CoV-2 infection and should not be discontinued. PROSPERO registration number: CRD42020186996.

© Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2020. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 17 Dec 2020; epub ahead of print
Lee MMY, Docherty KF, Sattar N, Mehta N, ... Jhund PS, McMurray JJV
Eur Heart J Cardiovasc Pharmacother: 17 Dec 2020; epub ahead of print | PMID: 33337478
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Impact:
Abstract

Antithrombotic therapy according to baseline bleeding risk in patients with atrial fibrillation undergoing percutaneous coronary intervention: applying the PRECISE-DAPT score in RE-DUAL PCI.

Costa F, Valgimigli M, Steg PG, Bhatt DL, ... Oldgren J, Cannon CP
Aims
Patients with atrial fibrillation undergoing coronary intervention are at higher bleeding risk due to the concomitant need for oral anticoagulation and antiplatelet therapy. The RE-DUAL PCI trial demonstrated better safety with dual antithrombotic therapy (DAT: dabigatran 110 or 150 mg bid, clopidogrel or ticagrelor) compared to triple antithrombotic therapy (TAT: warfarin, clopidogrel or ticagrelor, and aspirin). We explored the impact of baseline bleeding risk based on the PRECISE-DAPT score for decision-making regarding DAT vs. TAT.
Methods and results
A score ≥25 points qualified high bleeding-risk (HBR). Comparisons were made for the primary safety endpoint ISTH major or clinically relevant non-major bleeding, and the composite efficacy endpoint of death, thromboembolic events, or unplanned revascularization, analyzed by time-to-event analysis. PRECISE-DAPT was available in 2,336/2,725 patients, and 37.9% were HBR. Compared to TAT, DAT with dabigatran 110 mg reduced bleeding risk both in non-HBR (HR 0.42, 95%CI, 0.31-0.57) and HBR (HR 0.70, 95%CI, 0.52-0.94), with a greater magnitude of benefit among non-HBR (Pint=0.02). DAT with dabigatran 150 mg vs. TAT reduced bleeding in non-HBR (HR 0.60, 95%CI, 0.45-0.80), with a trend toward less benefit in HBR patients (HR 0.92, 95%CI, 0.63-1.34, Pint=0.08). Risk of ischaemic events was similar on DAT with dabigatran (both 110 and 150 mg) vs. TAT in non-HBR and HBR patients (Pint=0.45 and Pint=0.56, respectively).
Conclusions
PRECISE-DAPT score appeared useful to identify AF patients undergoing PCI at further increased risk of bleeding complications, and may help clinicians identifying the antithrombotic regimen intensity with the best benefit-risk ratio in an individual patient.

© Crown copyright 2020.

Eur Heart J Cardiovasc Pharmacother: 30 Nov 2020; epub ahead of print
Costa F, Valgimigli M, Steg PG, Bhatt DL, ... Oldgren J, Cannon CP
Eur Heart J Cardiovasc Pharmacother: 30 Nov 2020; epub ahead of print | PMID: 33258897
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Impact:
Abstract

Efficacy and safety of early initiation of eplerenone treatment in patients with acute heart failure (EARLIER trial): a multicenter, randomized, double-blind, placebo-controlled trial.

Asakura M, Ito S, Yamada T, Saito Y, ... Kitakaze M, EARLIER investigators and study coordinators
Aims
A mineralocorticoid receptor antagonist (MRA) is effective in patients with chronic heart failure; however, the effects of the early initiation of an MRA in patients with acute heart failure (AHF) have not been elucidated.
Methods and results
In this multicenter, randomized, double-blind, placebo-controlled, parallel-group study, we focused on the safety and effectiveness of the treatment with eplerenone, a selective MRA in 300 patients with AHF, that is, 149 in the eplerenone group and 151 in the placebo group in 27 Japanese institutions. The key inclusion criteria were (1) patients aged 20 years or older and (2) those with left ventricular ejection fraction of ≤ 40%. The primary outcome was a composite of cardiac death or first re-hospitalization due to cardiovascular disease within 6 months. The mean age of the participants was 66.8 years, 27.3% were women, and the median levels of brain natriuretic peptide were 376.0 pg/mL. The incidences of the primary outcome were 19.5% in the eplerenone group and 17.2% in the placebo group (hazard ratio (HR): 1.09, 95% confidence interval (CI): 0.642-1.855). In prespecified secondary outcomes, HR for the composite endpoint, cardiovascular death, or first re-hospitalization due to heart failure (HF) within 6 months was 0.55 (95% CI: 0.213 to 1.434). The safety profile for eplerenone was as expected.
Conclusion
The early initiation of eplerenone in patients with AHF could safely be utilized. The reduction of the incidence of a composite of cardiovascular death or first re-hospitalization for cardiovascular diseases by eplerenone is inconclusive because of inadequate power.

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Eur Heart J Cardiovasc Pharmacother: 10 Nov 2020; epub ahead of print
Asakura M, Ito S, Yamada T, Saito Y, ... Kitakaze M, EARLIER investigators and study coordinators
Eur Heart J Cardiovasc Pharmacother: 10 Nov 2020; epub ahead of print | PMID: 33175088
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Impact:
Abstract

Duration of dual antiplatelet therapy and subsequent monotherapy type in patients undergoing drug eluting stent implantation: a network Meta-analysis.

Benenati S, Crimi G, Canale C, Pescetelli F, ... Crea F, Porto I
Aims
To compare safety and efficacy of very short (≤3 months), short (6 months), standard (12 months) and extended (>12 months) DAPT, and subsequent monotherapies, after DES.
Methods and results
Twenty-two RCT (n = 110059 patients/year) were selected and included in a Bayesian network meta-analysis. The primary efficacy endpoint (PEP) was a composite of cardiac death, myocardial infarction (MI) and stent thrombosis (ST), the primary safety endpoint was major bleeding. Compared to standard, we found lower rate of MI (OR 0.56, 95% CI 0.44-0.77) in extended DAPT; lower rate of major bleeding (OR 0.61, 95% CI 0.39-0.87) in very short and lower rate of any bleeding (OR 0.61, 95% CI 0.38-0.90) in short DAPT. All DAPT durations were comparable regarding the secondary efficacy endpoints. Very short followed by P2Y12 inhibition was the treatment of choice to reduce both major bleeding and myocardial infarction. In the ACS subgroup, extended (as compared to standard DAPT) reduced PEP and ST (but not MI).
Conclusion
The efficacy of short and very short is comparable with that of standard DAPT after DES implantation, whereas extended DAPT reduces MI rate. Very short DAPT reduces haemorrhagic events and, followed by a P2Y12 inhibitor monotherapy, may be preferred in order to pursue a trade-off between major bleeding and ischemia.

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Eur Heart J Cardiovasc Pharmacother: 01 Nov 2020; epub ahead of print
Benenati S, Crimi G, Canale C, Pescetelli F, ... Crea F, Porto I
Eur Heart J Cardiovasc Pharmacother: 01 Nov 2020; epub ahead of print | PMID: 33135064
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Impact:
Abstract

EFFECT oF STATIN THERAPY oN SARS-CoV-2 INFECTION-RELATED.

Masana L, Correig E, Rodríguez-Borjabad C, Anoro E, ... Pedro-Botet J, Group OBOTSR
Aim
Assessing the effect of statin therapy at hospital admission for COVID-19 on in-hospital mortality.
Methods and results
Retrospective observational study. Patients taking statins were 11 years older and had significantly more comorbidities than patients who were not taking statins. A genetic matching (GM) procedure was performed prior to analysis of the mortality risk. A Cox proportional hazards model was used for the cause-specific hazard (CSH) function, and a competing-risks Fine and Gray (FG) model was also used to study the direct effects of statins on risk.Data from reverse transcription-polymerase chain reaction-confirmed 2157 SARS-CoV-2-infected patients (1234 men, 923 women; age: 67 y/o (IQR 54-78)) admitted to the hospital were retrieved from the clinical records in anonymized manner. 353 deaths occurred. 581 patients were taking statins. Univariate test after GM showed a significantly lower mortality rate in patients on statin therapy than the matched non-statin group (19.8% vs. 25.4%, χ2 with Yates continuity correction: p = 0.027). The mortality rate was even lower in patients (n = 336) who maintained their statin treatments during hospitalization compared to the GM non-statin group (17.4%; p = 0.045). The Cox model applied to the CSH function (HR = 0.58(CI: 0.39-0.89); p = 0.01) and the competing risks FG model (HR = 0.60(CI: 0.39-0.92); p = 0.02) suggest that statins are associated with reduced COVID-19-related mortality.
Conclusions
A lower SARS-CoV-2 infection-related mortality was observed in patients treated with statin therapy prior to hospitalization. Statin therapy should not be discontinued due to the global concern of the pandemic or in patients hospitalized for COVID-19.

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Eur Heart J Cardiovasc Pharmacother: 01 Nov 2020; epub ahead of print
Masana L, Correig E, Rodríguez-Borjabad C, Anoro E, ... Pedro-Botet J, Group OBOTSR
Eur Heart J Cardiovasc Pharmacother: 01 Nov 2020; epub ahead of print | PMID: 33135047
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Impact:
Abstract

Different left ventricular remodeling patterns and clinical outcomes between non-ischemic and ischemic etiologies in heart failure patients receiving sacubitril/valsartan treatment.

Lee YH, Chiou WR, Hsu CY, Lin PL, ... Lin WY, Chang HY
Aims
Although the beneficial effect of sacubitril/valsartan (SAC/VAL) compared to enalapril was consistent across ischaemic (ICM) and non-ischaemic cardiomyopathy (NICM) groups, the PARADIGM-HF study did not analyze the effect of ventricular remodelling on patients with different etiologies, which may affect clinical treatment outcomes. This study aimed to compare left ventricular ejection fraction (LVEF) following SAC/VAL treatment and its association with clinical outcomes.
Methods and results
A total of 1,576 patients were analyzed. Patients were grouped by LVEF changes following SAC/VAL treatment for 8-month period. LVEF improvement ≥15% was defined as \"significant improvement\", and <5% or worse was classified as \"lack of improvement\". The primary outcome was a composite of cardiovascular death and unplanned hospitalization for heart failure.Patients with NICM had lower baseline LVEF but improvement was significantly greater comparing to those with ICM (baseline 28.0 ± 7.7% vs. 30.1 ± 7.1%, p < 0.001, LVEF increase of 11.1 ± 12.6% vs. 6.7 ± 10.2%, p < 0.001). The effect of functional improvement of SAC/VAL on NICM patients showed bimodal distribution. Primary endpoints were inversely associated with LVEF changes in NICM patients: adjusted hazard ratio was 0.42 (95% confidence interval [CI] 0.31-0.58, p < 0.001) for NICM patients with significant improvement, and was 1.73 (95% CI 1.38-2.16, p < 0.001) for NICM patients but lack of improvement. Primary endpoints of ICM patients did not demonstrate an association with LVEF changes.
Conclusion
Patients with NICM had higher degree of LVEF improvement than those with ICM following SAC/VAL treatment, and significant improvement of LVEF in NICM patients indicates favorable outcome.

© Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2020. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 28 Oct 2020; epub ahead of print
Lee YH, Chiou WR, Hsu CY, Lin PL, ... Lin WY, Chang HY
Eur Heart J Cardiovasc Pharmacother: 28 Oct 2020; epub ahead of print | PMID: 33119090
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Impact:
Abstract

The burden of cholesterol accumulation through the lifespan: why pharmacological intervention should start earlier to go further?

Zambon A, Mello E Silva A, Farnier M
Among the cardiovascular risk factors, cholesterol-rich atherogenic lipoproteins play a central role in the pathogenesis of atherosclerosis. In middle-aged adults, the size of the total atherosclerotic plaque burden is influenced by both the concentration of circulating atherogenic lipoproteins and by the total duration of exposure to these lipoproteins. This review describes the evidence supporting a causal link between life-long elevations in atherogenic lipoproteins and future risk of atherosclerosis; evidence strengthened by recent epidemiological, genetic and clinical data. By consequence, adolescence and early adulthood are a crucial time for determining later cardiovascular disease risk. Arguments showing that early optimal lipid control leads to improved outcomes will be presented, and suggestions put forward for how those most at risk should be identified and managed.

© Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2020. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 28 Oct 2020; epub ahead of print
Zambon A, Mello E Silva A, Farnier M
Eur Heart J Cardiovasc Pharmacother: 28 Oct 2020; epub ahead of print | PMID: 33119073
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Impact:
Abstract

Depressive symptoms and non-adherence to treatable cardiovascular risk factors\' medications in the CONSTANCES cohort.

Hamieh N, Kab S, Zins M, Blacher J, ... Melchior M, Lemogne C
Aims
Depression is associated with increased risk of cardiovascular disease (CVD) and the role of poor medical adherence is mostly unknown. We studied the association between depressive symptoms and non-adherence to medications targeting treatable cardiovascular risk factors in the CONSTANCES population-based French cohort.
Methods and results
We used CONSTANCES data linked to the French national healthcare database to study the prospective association between depressive symptoms (assessed at inclusion with the Center for Epidemiological Studies Depression scale) and non-adherence to medications (less than 80% of trimesters with at least one drug dispensed) treating type 2 diabetes, hypertension, and dyslipidaemia over 36 months of follow-up. Binary logistic regression models were adjusted for socio-demographics, body mass index, and personal history of CVD at inclusion. Among 4998 individuals with hypertension, 793 with diabetes, and 3692 with dyslipidaemia at baseline, respectively 13.1% vs. 11.5%, 10.5% vs. 5.8%, and 29.0% vs. 27.1% of those depressed vs. those non-depressed were non-adherent over the first 18 months of follow-up (15.9% vs. 13.6%, 11.1% vs. 7.4%, and 34.8% vs. 36.6% between 19 and 36 months). Adjusting for all covariates, depressive symptoms were neither associated with non-adherence to medications for hypertension, diabetes, and dyslipidaemia over the first 18 months of follow-up, nor afterwards. Depressive symptoms were only associated with non-adherence to anti-diabetic medications between the first 3-6 months of follow-up.
Conclusion
Non-adherence to medications targeting treatable cardiovascular risk factors is unlikely to explain much of the association between depressive symptoms and CVD at a population level. Clinicians are urged to search for and treat depression in individuals with diabetes to foster medications adherence.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 27 Oct 2020; epub ahead of print
Hamieh N, Kab S, Zins M, Blacher J, ... Melchior M, Lemogne C
Eur Heart J Cardiovasc Pharmacother: 27 Oct 2020; epub ahead of print | PMID: 33200205
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Impact:
Abstract

Effect of Ticagrelor Monotherapy on Mortality After PCI: A Systematic Review and Meta-Analysis of Randomized Trials Including 26143 patients.

Hong SJ, Ahn CM, Kim JS, Kim BK, ... Jang Y, Hong MK
Background
Optimal timing and strategy of antiplatelet monotherapy after dual-antiplatelet therapy (DAPT) consisting of aspirin and P2Y12 inhibitor for patients who underwent percutaneous coronary intervention (PCI) is still being debated. The aim of this study to evaluate the effect of ticagrelor monotherapy after short-term DAPT after PCI on mortality.
Methods and results
A systematic review and meta-analysis was performed using PubMed to search for ticagrelor monotherapy after short-term DAPT comparing conventional DAPT in patients who underwent PCI. Three randomized trials encompassing 26143 patients (ticagrelor monotherapy after 1 to 3 months of DAPT [n = 13062] vs. conventional therapy [n = 13081]) were included. The efficacy endpoint of all-cause mortality was significantly lower with the ticagrelor monotherapy group vs. the conventional therapy group (risk ratio [RR]=0.80, 95% confidence interval [CI]=0.65 - 0.98; P = 0.03; I2=0%; number needed to treat for benefit [NNTB]=320). The safety endpoint of Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding was also significantly lower with the ticagrelor monotherapy group vs. the conventional therapy group (RR = 0.67, 95% CI = 0.49 - 0.92; P = 0.01; I2=65%; NNTB = 156). There were no significant differences in ischaemic stroke, acute myocardial infarction, and stent thrombosis. The favorable effects of the ticagrelor monotherapy vs. the conventional therapy on all-cause mortality and BARC type 3 or 5 bleeding were consistent in the subset of patients presenting acute coronary syndromes (n = 15157).
Conclusion
Ticagrelor monotherapy after short-term DAPT of 1 to 3 months was associated with decreased all-cause mortality and BARC type 3 or 5 bleeding not offset by increase of cardiac death, ischaemic stroke, acute myocardial infarction, and stent thrombosis.

© Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2020. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 08 Oct 2020; epub ahead of print
Hong SJ, Ahn CM, Kim JS, Kim BK, ... Jang Y, Hong MK
Eur Heart J Cardiovasc Pharmacother: 08 Oct 2020; epub ahead of print | PMID: 33035298
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Impact:
Abstract

Effectiveness and Safety of Oral Anticoagulants Among Non-Valvular Atrial FibrillationPatients with Polypharmacy.

Lip GYH, Keshishian A, Kang A, Dhamane AD, ... Yuce H, Deitelzweig S
Aims
Polypharmacy is prevalent among non-valvular atrial fibrillation (NVAF) patients and presents a potential issue for the effective management of NVAF. This study compared the risk of stroke/systemic embolism (SE) and major bleeding (MB) among NVAF patients with polypharmacy newly prescribed oral anticoagulants (OACs).
Methods and results
A retrospective study of NVAF patients with polypharmacy who initiated OACs from 01JAN2013-30SEP2015 was conducted using US CMS Medicare and four commercial databases. Polypharmacy was defined as ≥ 6 concomitant medications on the index date. Propensity score matching was conducted to compare non-Vitamin K antagonists OACs (NOACs) to warfarin as well as between NOACs. Cox proportional hazard models were used to evaluate the risk of stroke/SE and MB. A total of 188,893 patients with polypharmacy were included, with an average of 8 concomitant medications (IQR 6-9). Compared to warfarin, apixaban (HR: 0.59, 95% CI: 0.52-0.68) and rivaroxaban (HR: 0.75, 95% CI: 0.69-0.83) were associated with a lower risk of stroke/SE. Apixaban (HR: 0.57, 95% CI: 0.54-0.61) and dabigatran (HR: 0.76, 95% CI: 0.66-0.88) were associated with a decreased risk of MB compared with warfarin. Compared with dabigatran and rivaroxaban, apixaban was associated with a lower risk of stroke/SE and MB. Dabigatran was associated with lower risk of MB compared with rivaroxaban.
Conclusions
In this observational study of anticoagulated NVAF patients with polypharmacy, effectiveness and safety profiles are more favorable for NOACs vs warfarin. Our observations are hypothesis generating and may help inform future clinical trials regarding appropriate OAC treatment selection in polypharmacy patients.

© Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2020. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 02 Oct 2020; epub ahead of print
Lip GYH, Keshishian A, Kang A, Dhamane AD, ... Yuce H, Deitelzweig S
Eur Heart J Cardiovasc Pharmacother: 02 Oct 2020; epub ahead of print | PMID: 33010157
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Impact:
Abstract

Medication in adults after atrial switch for transposition of the great arteries: clinical practice and recommendations.

Woudstra OI, Kuijpers JM, Jongbloed MRM, van Dijk APJ, ... Mulder BJM, Bouma BJ
Aims
Heart failure is the main threat to long-term health in adults with transposition of the great arteries(TGA) corrected by an atrial switch operation(AtrSO). Current guidelines refrain from recommending heart failure medication in TGA-AtrSO, as there is insufficient data to support the hypothesis that it is beneficial. Medication is therefore prescribed based on personal judgements. We aimed to evaluate medication use in TGA-AtrSO patients and examine the association of use of Renin-Angiotension-Aldosteron System(RAAS) inhibitors and β-blockers with long-term survival.
Methods and results
We identified 150 TGA-AtrSO patients(median age 30 years[IQR 25-35], 63% male) included in the CONCOR registry from five tertiary medical centers with subsequent linkage to the Dutch Dispensed Drug Register for the years 2006-2014. Use of RAAS inhibitors, β-blockers, and diuretics increased with age, from respectively 21%[95%CI 14-40], 12%[95%CI 7-21], and 3%[95%CI 2-7] at age 25, to 49%[95%CI 38-60], 51%[95%CI 38-63], and 41%[95%CI 29-54] at age 45. Time-varying Cox marginal structural models that adjusted for confounding medication showed a lower mortality risk with use of RAAS inhibitors and β-blockers in symptomatic patients(HR = 0.13[95%CI 0.03-0.73]; p=0.020 and HR = 0.12[95%CI 0.02-0.17]; p=0.019, respectively). However, in the overall cohort, no benefit of RAAS inhibitors and β-blockers was seen(HR = 0.93[95%CI 0.24-3.63]; p=0.92 and HR = 0.98[0.23-4.17]; p=0.98, respectively).
Conclusion
The use of heart failure medication is high in TGA-AtrSO patients, although evidence of its benefit is limited. This study showed lower risk of mortality with use of RAAS inhibitors and β-blockers in symptomatic patients only. These findings can direct future guidelines, supporting use of RAAS inhibitors and β-blockers in symptomatic, but not asymptomatic patients.

© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J Cardiovasc Pharmacother: 24 Sep 2020; epub ahead of print
Woudstra OI, Kuijpers JM, Jongbloed MRM, van Dijk APJ, ... Mulder BJM, Bouma BJ
Eur Heart J Cardiovasc Pharmacother: 24 Sep 2020; epub ahead of print | PMID: 32976560
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Impact:
Abstract

Impact of White Blood Cell Count on Clinical Outcomes in Patients Treated with Aspirin-Free Ticagrelor Monotherapy after Percutaneous Coronary Intervention: Insights from the GLOBAL LEADERS Trial.

Ono M, Tomaniak M, Koenig W, Khamis R, ... Serruys PW, GLOBAL LEADERS Study Investigators
Aims
To investigate the efficacy and safety of ticagrelor monotherapy in patients undergoing percutaneous coronary intervention (PCI) stratified according to the baseline white blood cell (WBC) count.
Methods and results
This is a post-hoc analysis of the GLOBAL LEADERS trial, a multicentre, open-label, randomized all-comer trial in patients undergoing PCI, comparing the experimental strategy (23-month ticagrelor monotherapy following 1-month dual anti-platelet therapy [DAPT]) with the reference strategy (12-month aspirin monotherapy following 12-month DAPT). Patients were stratified into two WBC groups, either < or ≥median WBC count of 7.8 x 109 cells/L (lower or higher WBC group, respectively). The primary endpoint was a composite of all-cause mortality or new Q-wave myocardial infarction (MI) at 2 years.Out of 14,576 patients included in the present study, 7,212 patients (49.5%) were classified as the lower WBC group, who had a significantly lower risk of both ischemic and bleeding outcomes at 2 years. At 2 years, the experimental strategy was associated with a significant lower incidence of the primary endpoint compared with the reference strategy in the lower WBC group (2.8% vs. 4.2%; hazard ratio [HR]: 0.67; 95% CI: 0.52-0.86) but not in the higher WBC group (4.8% vs. 4.7%; HR: 1.01; 95% CI: 0.82-1.25; pinteraction=0.013). There were no significant differences in the risks of BARC type 3 or 5 bleeding between two antiplatelet strategies regardless of the WBC groups.
Conclusions
Increased WBC counts, which may reflect degree of inflammation, at the time of index procedure may attenuate the anti-ischemic benefits of ticagrelor monotherapy observed in patients with lower WBC counts.

© Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2020. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 20 Sep 2020; epub ahead of print
Ono M, Tomaniak M, Koenig W, Khamis R, ... Serruys PW, GLOBAL LEADERS Study Investigators
Eur Heart J Cardiovasc Pharmacother: 20 Sep 2020; epub ahead of print | PMID: 32956446
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Impact:
Abstract

PRECISE-DAPT score for bleeding risk prediction in patients on dual or single antiplatelet regimens: insights from the GLOBAL LEADERS and GLASSY.

Gragnano F, Heg D, Franzone A, McFadden EP, ... Valgimigli M, GLASSY Investigators
Aims
The 5-item PRECISE-DAPT, integrating age, haemoglobin, white-blood-cell count, creatinine clearance, and prior bleeding, predicts bleeding risk in patients on dual antiplatelet therapy (DAPT) after stent implantation. We sought to assess whether the bleeding risk prediction offered by the PRECISE-DAPT remains valid among patients receiving ticagrelor monotherapy from 1 month onwards after coronary stenting instead of standard DAPT and having or not having centrally-adjudicated bleeding endpoints.
Methods and results
The PRECISE-DAPT was calculated in 14,928 and 7,134 patients from GLOBAL LEADERS and GLASSY trials, respectively. The ability of the score to predict BARC 3 or 5 bleeding was assessed and compared among patients on ticagrelor monotherapy (experimental strategy) or standard DAPT (reference strategy) from 1 month after drug-eluting stent implantation. Bleeding endpoints were investigator-reported or centrally-adjudicated in GLOBAL LEADERS and GLASSY, respectively.At 2 years, the c-indexes for the score among patients treated with the experimental or reference strategy were 0.67 (95% confidence interval [CI]:0.63-0.71) vs. 0.63 (95% CI:0.59-0.67) in GLOBAL LEADERS (p = 0.27), and 0.67 (95% CI:0.61-0.73) vs. 0.66 (95% CI:0.61-0.72) in GLASSY (p = 0.88). Decision curve analysis showed net benefit using the PRECISE-DAPT to guide bleeding risk assessment under both treatment strategies. Results were consistent between investigator-reported and adjudicated endpoints and using the simplified 4-item PRECISE-DAPT.
Conclusions
The PRECISE-DAPT offers a prediction model that proved similarly effective to predict clinically-relevant bleeding among patients on ticagrelor monotherapy from 1 month after coronary stenting compared with standard DAPT and appears to be unaffected by the presence or absence of adjudicated bleeding endpoints.

© Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2020. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 16 Sep 2020; epub ahead of print
Gragnano F, Heg D, Franzone A, McFadden EP, ... Valgimigli M, GLASSY Investigators
Eur Heart J Cardiovasc Pharmacother: 16 Sep 2020; epub ahead of print | PMID: 32941620
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Impact:
Abstract

Potentially Inappropriate Prescriptions in Heart Failure with Reduced Ejection Fraction (PIP-HFrEF).

El Hadidi S, Rosano G, Tamargo J, Agewall S, ... Lewis BS, Coats AJS
Heart failure (HF) is a chronic debilitating and potentially life-threatening condition. Heart Failure patients are usually at high risk of polypharmacy and consequently, potentially inappropriate prescribing leading to poor clinical outcomes. Based on the published literature, a comprehensive HF-specific prescribing review tool is compiled to avoid medications that may cause HF or harm HF patients and to optimize the prescribing practice of HF guideline-directed medical therapies. Recommendations are made in line with the last versions of ESC guidelines, ESC position papers, scientific evidence, and experts\' opinions.

© Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2020. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 16 Sep 2020; epub ahead of print
El Hadidi S, Rosano G, Tamargo J, Agewall S, ... Lewis BS, Coats AJS
Eur Heart J Cardiovasc Pharmacother: 16 Sep 2020; epub ahead of print | PMID: 32941594
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Impact:
Abstract

Unravelling the puzzle of antithrombotic therapies for complex percutaneous coronary intervention.

De Luca L, Valgimigli M
Percutaneous coronary intervention (PCI) has remarkably evolved in the last decades. This has resulted in a larger number of patients treated with PCI, including those with more complex anatomic lesions. Several studies demonstrated that PCI involving complex lesions is associated with increased rate of procedural complications and adverse clinical outcomes. In this setting, optimal adjunctive antithrombotic regimens still need to be defined. In this review, we sought to summarize and discuss the recent evidence deriving from analyses appraising antithrombotic therapies in patients undergoing complex PCI.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 15 Sep 2020; epub ahead of print
De Luca L, Valgimigli M
Eur Heart J Cardiovasc Pharmacother: 15 Sep 2020; epub ahead of print | PMID: 33175148
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Impact:
Abstract

Management of pregnancy-related hypertensive disorders in patients infected with SARS CoV-2: pharmacological and clinical issues.

Fogacci S, Fogacci F, Favari E, Toth PP, Borghi C, Cicero AFG
Coronavirus-19 disease (COVID-19) continues to spread throughout the world. It is known that among patients with hypertension, diabetes, chronic respiratory disease, or cardiovascular diseases, COVID-19 is associated with greater morbidity and mortality compared with patients without these conditions. This correlation is of great importance in pregnant women affected by COVID-19, since it usually leads to the development of a serious clinical complication. In particular, managing hypertensive disorders in pregnancy can be problematic because antihypertensive medications may interact pharmacologically with drugs used to treat COVID-19. This review focuses on the safety of drug treatment for COVID-19 in pregnant women treated with antihypertensive medication. Several databases were searched to identify relevant literature. A few antihypertensive drugs and antithrombotic treatments are known for having a beneficial effect in the management of hypertension and hypertensive disorders in pregnancy. In this review, we focus on the expected drug-drug interactions with the experimental agents most often used to treat COVID-19. The current indications for the management of hypertension-related disorders in pregnancy maintain their validity, while the risk of pharmacological interaction with the currently tested anti-SARS-CoV-2 medications is relatively low.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 09 Sep 2020; epub ahead of print
Fogacci S, Fogacci F, Favari E, Toth PP, Borghi C, Cicero AFG
Eur Heart J Cardiovasc Pharmacother: 09 Sep 2020; epub ahead of print | PMID: 33155016
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Impact:
Abstract

Off-label use of reduced dose direct oral factor Xa-inhibitors in subjects with atrial fibrillation: a review of clinical evidence.

Bo M, Corsini A, Brunetti E, Isaia G, ... Marchionni N, De Ferrari GM
In real-world clinical practice, underdosing, i.e. off-label use of reduced doses (RD), of oral factor Xa inhibitors (oFXaIs) is quite common in stroke prevention in nonvalvular atrial fibrillation, possibly reflecting the hope to increase safety without reducing efficacy in selected patients. To assess whether this strategy is associated with some clinical benefit, we used a physician-centered approach to evaluate whether current evidence supports the hypothesis that a substantial proportion of underdosing may be voluntary rather than casual, whether and to what extent oFXaIs\' dose rather than patients\' characteristics are associated with bleeding events, and which are the safety and efficacy clinical implications of oFXaIs\' underdosing. Our review found consistent evidence that underdosing is often an intentional strategy; however, available studies do not demonstrate a sizeable net clinical benefit of using off-label RD oFXaIs.

© Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2020. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 26 Aug 2020; epub ahead of print
Bo M, Corsini A, Brunetti E, Isaia G, ... Marchionni N, De Ferrari GM
Eur Heart J Cardiovasc Pharmacother: 26 Aug 2020; epub ahead of print | PMID: 32853346
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Impact:
Abstract

Optimal P2Y12 inhibition in older adults with acute coronary syndromes: A network meta-analysis of randomized controlled trials.

Montalto C, Morici N, Munafò AR, Mangieri A, ... De Servi S, Crimi G
Aims
Dual antiplatelet therapy (DAPT) with a P2Y12 inhibitor on top of aspirin is the cornerstone of therapy after acute coronary syndromes (ACS). Nonetheless, the safest and most efficacious P2Y12 for older patients who are both at high ischemic and bleeding risk remains uncertain. We aimed to examine the effect of available P2Y12 inhibitors on ischemic and bleeding endpoints in older adults with ACS.
Methods and results
Randomized clinical trials that reported separately the results of adults older >70 years for at least the primary endpoint (composite of death, myocardial infarction [MI] and stroke). Seven studies (14,485 patients-years) were included. Network meta-analysis showed that prasugrel was associated with similar occurrence of the primary endpoint and of a secondary ischemic endpoint (composite of MI and stroke) and was most likely the best treatment (Surface Under the Cumulative Ranking curve Analysis [SUCRA] 54.5 and 59.8, respectively). With regards to major bleedings, clopidogrel showed the highest likelihood of event reduction (SUCRA 70.1%) while ticagrelor of stent thrombosis (SUCRA 55.6%). Our meta-regression with a fixed proportion of patients managed invasively of 100% confirmed these trends with increasing SUCRA.
Conclusion
Among older subjects with ACS, DAPT should be balanced upon ischemic and bleeding risks as prasugrel is associated with the highest probability of reduction of ischemic events and clopidogrel of bleedings. Ticagrelor had highest SUCRA for stent thrombosis reduction but seems suboptimal in older adults.

© Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2020. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 23 Aug 2020; epub ahead of print
Montalto C, Morici N, Munafò AR, Mangieri A, ... De Servi S, Crimi G
Eur Heart J Cardiovasc Pharmacother: 23 Aug 2020; epub ahead of print | PMID: 32835355
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Impact:
Abstract

Patient-Reported Outcomes and Medication Adherence in Patients with Heart Failure.

Rasmussen AA, Wiggers H, Jensen M, Berg SK, ... Larsen SH, Johnsen SP
Aim
Patient-reported outcome measures (PROMs) may predict poor clinical outcome in patients with heart failure (HF). It remains unclear whether PROMs are associated with subsequent adherence to HF medication. We aimed to determine whether health-related quality of life, anxiety and depression were associated with long-term medication adherence in these patients.
Methods and results
A national cohort study of Danish patients with HF with three-year follow-up (n = 1,464). PROMs included the EuroQol five-dimensional, five-level questionnaire (EQ-5D-5L), the HeartQoL and the Hospital Anxiety and Depression Scale (HADS). Patient-reported outcomes (PRO) data were linked to demographic and clinical data at baseline, and data on all redeemed prescriptions for angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers/angiotensin receptor neprilysin inhibitors (ACEI/ARB/ARNI), β-blockers and mineralocorticoid receptor antagonists (MRAs) during follow-up. Medication non-adherence was defined as < 80% of proportion of days covered (PDC). In adjusted regression analyses, lower health-related quality of life (EQ-5D and HeartQoL) and symptoms of depression (HADS-D) at discharge were associated with non-adherence. After three years of follow-up, lower health-related quality of life (EQ-5D) was associated with non-adherence for ACEI/ARB/ARNI (adjusted OR 2.78, 95% CI:1.19-6.49), β-blockers (adjusted OR 2.35, 95% CI:1.04-5.29), whereas HADS-D was associated with non-adherence for ACEI/ARB/ARNI (adjusted OR 1.07, 95% CI:1.03-1.11) and β-blockers (adjusted OR 1.06, 95% CI:1.02-1.10).
Conclusion
Lower health-related quality of life and symptoms of depression were associated with non-adherence across HF medications at one- and three years of follow-up. Person-centred care using PROMs may carry a potential for identifying patients at increased risk of future medication non-adherence.

© Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2020. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 05 Aug 2020; epub ahead of print
Rasmussen AA, Wiggers H, Jensen M, Berg SK, ... Larsen SH, Johnsen SP
Eur Heart J Cardiovasc Pharmacother: 05 Aug 2020; epub ahead of print | PMID: 32761093
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Impact:
Abstract

Ticagrelor and The Risk of Staphylococcus Aureus Bacteremia and Other Infections.

Butt JH, Fosbøl EL, Gerds TA, Iversen K, ... Køber L, Olesen JB
Aim
To investigate the 1-year risks of Staphylococcus aureus bacteremia (SAB), sepsis, and pneumonia in patients who underwent percutaneous coronary intervention and were treated with ticagrelor versus clopidogrel.
Methods and results
In this nationwide observational cohort study, 26,606 patients who underwent urgent or emergent percutaneous coronary intervention (January 2011-December 2017) and initiated treatment with ticagrelor (N = 20,073 [75.5%]; median age 64 years [25th-75th percentile 55-72 years]; 74.8% men) or clopidogrel (N = 6,533 [24.5%]; median age 68 years [25th-75th percentile 58-77 years]; 70.2% men) were identified using Danish nationwide registries. The 1-year standardized absolute risks of outcomes was calculated based on cause-specific Cox regression models, and average treatment effects between treatment groups were obtained as standardized differences in absolute 1-year risks. The absolute 1-year risk of SAB was 0.10% [95% CI, 0.05% to 0.15%] in the ticagrelor group and 0.29% [95% CI, 0.17% to 0.42%] in the clopidogrel group. Compared with clopidogrel, treatment with ticagrelor was associated with a significantly lower absolute 1-year risk of SAB (absolute risk difference -0.19% [95% CI, -0.32% to -0.05%], p-value 0.006). Likewise, treatment with ticagrelor was associated with a significantly lower absolute 1-year risk of sepsis (0.99% [95% CI, 0.83% to 1.14% versus 1.49% [95%CI, 1.17% to 1.80%]; absolute risk difference -0.50% [95% CI, -0.86% to -0.14%], p-value 0.007) and pneumonia (3.13% [95%CI, 2.86% to 3.39% versus 4.56% [95%CI, 4.03% to 5.08%]; absolute risk difference -1.43% [95% CI, -2.03% to -0.82%], p-value < 0.001) compared with clopidogrel.
Conclusions
Treatment with ticagrelor was associated with a significantly lower 1-year risk of SAB, sepsis, and pneumonia compared with clopidogrel.

© Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2020. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 03 Aug 2020; epub ahead of print
Butt JH, Fosbøl EL, Gerds TA, Iversen K, ... Køber L, Olesen JB
Eur Heart J Cardiovasc Pharmacother: 03 Aug 2020; epub ahead of print | PMID: 32750138
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Impact:
Abstract

Impact of opioids on P2Y12-receptor inhibition in patients with ST-elevation myocardial infarction who are pre-treated with crushed ticagrelor: Opioids aNd crushed Ticagrelor In Myocardial infarction Evaluation (ON-TIME 3) trial.

Tavenier AH, Hermanides RS, Ottervanger JP, Tolsma R, ... Ruiters L, van \'t Hof AWJ
Aim
Platelet inhibition induced by P2Y12 receptor antagonists in patients with ST-elevation myocardial infarction (STEMI) can be affected by concomitant use of opioids. The aim of this trial was to examine the effect of intravenous (iv) acetaminophen compared with iv fentanyl on P2Y12 receptor inhibition in patients with STEMI.
Methods and results
The ON-TIME 3 trial randomised 195 STEMI patients who were scheduled to undergo primary percutaneous coronary intervention (PCI) and were pre-treated with crushed ticagrelor to iv acetaminophen (N = 98) or iv fentanyl (N = 97) in the ambulance.The primary endpoint, consisting of the level of platelet reactivity units (PRU) measured immediately after primary PCI, was not significantly different between the study arms (median PRU 104 [IQR 37-215] vs. 175 [63-228], P = 0.18). However, systemic levels of ticagrelor were significantly higher in the acetaminophen arm at the start of primary PCI (151 ng/mL [32-509] vs. 60 ng/mL [13-206], P = 0.007), immediately after primary PCI (326 ng/mL [94-791] vs. 115 ng/mL [38-326], P = 0.002) and at one-hour after primary PCI (488 ng/mL [281-974]) vs. 372 ng/mL [95-635], P = 0.002). Acetaminophen resulted in the same extent of pain relief as compared to fentanyl (reduction of 3 points on 10-step-pain scale before primary PCI [IQR 1-5] in both study arms (P = 0.67) and immediately after PCI (reduction of 5 points [3-7]; P = 0.96).
Conclusion
Iv acetaminophen in comparison with iv fentanyl was not associated with significantly lower platelet reactivity in STEMI patients, but resulted in significantly higher ticagrelor plasma levels and was effective in pain relief.

© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J Cardiovasc Pharmacother: 29 Jul 2020; epub ahead of print
Tavenier AH, Hermanides RS, Ottervanger JP, Tolsma R, ... Ruiters L, van 't Hof AWJ
Eur Heart J Cardiovasc Pharmacother: 29 Jul 2020; epub ahead of print | PMID: 32730628
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Impact:
Abstract

The Use of Novel Oral Anti-Coagulant\'s (NOAC) compared to Vitamin K Antagonists (Warfarin) in patients with Left Ventricular thrombus after Acute Myocardial Infarction (AMI).

Jones DA, Wright P, Alizadeh MA, Fhadil S, ... Mathur A, Antoniou S
Aim
Current guidelines recommend the use of Vitamin K Antagonist (VKA) for up to 3 - 6 months for treatment of LV thrombus post-acute myocardial infarction (AMI). However, based on evidence supporting non-inferiority of Novel Oral Anti-Coagulant\'s (NOAC) compared to VKA for other indications such as DVT, PE and thrombo-embolic prevention in atrial fibrillation, NOACs are being increasingly used off licence for the treatment of LV thrombus post AMI. In this study we investigated the safety and effect of NOACs compared to VKA on LV thrombus resolution in patients presenting with AMI.
Methods and results
This was an observational study of 2,328 consecutive patients undergoing Coronary Angiography +/- Percutaneous Coronary Intervention (PCI) for AMI between May 2015- December 2018, at a UK cardiac centre. Patients\' details were collected from the hospital electronic database. The primary end-point was rate of LV thrombus resolution with bleeding rates a secondary outcome.Left ventricular (LV) thrombus was diagnosed in 101 (4.3%) patients. Sixty patients (59.4%) were started on VKA and 41 patients (40.6%) on NOAC therapy (rivaroxaban: 58.5%, apixaban, 36.5% and edoxaban: 5.0%). Both groups were well matched in terms of baseline characteristics including age, previous cardiac history (Previous MI, PCI, CABG), and cardiovascular risk factors (Hypertension, Diabetes, Hypercholesterolaemia).Over the follow up period (median 2.2 years), overall rates of LV thrombus resolution were 86.1%. There was greater and earlier LV thrombus resolution in the NOAC group compared to patients treated with warfarin (82% vs 64.4%, p = 0.0018, at 1 year), which persisted after adjusting for baseline variables (OR 1.8 95% CI 1.2-2.9). Major bleeding events during the f/u period were lower in the NOAC group, compared with VKA group (0% vs 6.7%, p = 0.030) with no difference in rates of systemic thromboembolism (5% vs 2.4%, p = 0.388).
Conclusion
This data suggests improved thrombus resolution in post ACS LV thrombosis in patients treated with NOACs compared to vitamin K antagonists. This improvement in thrombus resolution was accompanied with a better safety profile for NOAC patients\' vs VKA treated patients. Thus, provides data to support a randomised trial to answer this question.

© Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2020. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 29 Jul 2020; epub ahead of print
Jones DA, Wright P, Alizadeh MA, Fhadil S, ... Mathur A, Antoniou S
Eur Heart J Cardiovasc Pharmacother: 29 Jul 2020; epub ahead of print | PMID: 32730627
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Impact:
Abstract

Risk of Fracture in Patients with Nonvalvular Atrial Fibrillation Initiating Direct Oral Anticoagulants vs Vitamin K Antagonists.

He N, Dell\'Aniello S, Zhai S, Suissa S, Renoux C
Aims
To determine the risk of fracture associated with direct oral anticoagulants (DOACs) compared with vitamin K antagonists (VKAs) in patients with nonvalvular atrial fibrillation (NVAF), accounting for cumulative duration of use.
Methods and results
Using Quebec administrative healthcare databases, we formed a cohort of all patients aged 40 years or older newly diagnosed with NVAF, who filled a first prescription for DOACs or VKAs between 2011 and 2014. Exposure was modelled as a time-varying variable whereby patients were considered unexposed up to 180 days of cumulative duration of use (to account for a biologically meaningful exposure) and exposed thereafter. The final cohort included 10,306 new users of DOACs and 15,357 new users of VKAs. After propensity score-based fine stratification and weighting, use of DOACs for 180 days or greater was associated with a 35% decreased risk of fracture (crude incidence rates 7.5 vs 15.3 per 1000 person-years; adjusted hazard ratio [HR] 0.65, 95%CI 0.46 - 0.91) compared to VKA duration ≥ 180 days. DOACs use was also associated with a lower risk of hip fracture (HR 0.51, 95%CI 0.31 - 0.86) compared with VKAs. There was no difference in the rate of fracture for shorter duration of use (HR 1.10; 95%CI 0.79 - 1.53). The risk was not modified by age, sex, chronic kidney disease, osteoporosis, history of fracture or falls.
Conclusion
Prolonged use of DOACs is associated with a lower risk of fracture compared with VKAs. These findings support the first-line recommendation for DOACs in patients with NVAF.

© Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2020. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 27 Jul 2020; epub ahead of print
He N, Dell'Aniello S, Zhai S, Suissa S, Renoux C
Eur Heart J Cardiovasc Pharmacother: 27 Jul 2020; epub ahead of print | PMID: 32722764
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Impact:
Abstract

Central Apnoeas and Ticagrelor Related Dyspnoea in Patients with Acute Coronary Syndrome.

Giannoni A, Borrelli C, Gentile F, Mirizzi G, ... Emdin M, Passino C
Aims
Dyspnoea often occurs in patients with acute coronary syndrome (ACS) treated with ticagrelor compared to other anti-platelet agents, and is a cause of drug discontinuation. We aimed to explore the contribution of central apnoeas and chemoreflex sensitization to ticagrelor-related dyspnoea in patients with ACS.
Methods and results
Sixty consecutive patients with ACS, preserved left ventricular ejection fraction and no history of obstructive sleep apnoea, treated either with ticagrelor 90 mg b.i.d. (n = 30) or prasugrel 10 mg o.d. (n = 30) were consecutively enrolled. One week after ACS, all patients underwent 2-dimensional Doppler echocardiography, pulmonary static/dynamic testing, carbon monoxide diffusion capacity assessment, 24-hour cardiorespiratory monitoring for hypopnoea-apnoea detection, and evaluation of the chemosensitivity to hypercapnia by rebreathing technique.No differences were found in baseline demographic and clinical characteristics, echocardiographic and pulmonary data between the 2 groups. Patients on ticagrelor, as compared to those on prasugrel, reported more frequently dyspnoea (43.3% versus 6.7%, p = 0.001; severe dyspnoea 23.3% versus 0%, p = 0.005), and showed higher apnoea-hypopnoea index (AHI) and central apnoea index (CAI) during the day, the night and the entire 24-hour period (all p < 0.001). Likewise, they showed a higher chemosensitivity to hypercapnia (p = 0.001). Among patients treated with ticagrelor, those referring dyspnoea had the highest AHI, CAI and chemosensitivity to hypercapnia (all p < 0.05).
Conclusions
Central apnoeas are a likely mechanism of dyspnoea and should be screened for in patients treated with ticagrelor. A drug related sensitization of the chemoreflex may be the cause of ventilatory instability and breathlessness in this setting.

© Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2020. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 14 Jul 2020; epub ahead of print
Giannoni A, Borrelli C, Gentile F, Mirizzi G, ... Emdin M, Passino C
Eur Heart J Cardiovasc Pharmacother: 14 Jul 2020; epub ahead of print | PMID: 32667975
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Impact:
Abstract

Prediction of the early response to spironolactone in resistant hypertension by the combination of matrix metalloproteinase-9 activity and arterial stiffness parameters.

Rodríguez-Sánchez E, Navarro-García JA, Aceves-Ripoll J, González-Lafuente L, ... Ruilope LM, Ruiz-Hurtado G
Aims
The aim of present study was to determine whether arterial stiffness assessed with the biochemical parameter active matrix metalloproteinase (MMP)-9 and the clinical parameters pulse pressure (PP) and pulse wave velocity predicts the response to spironolactone in resistant hypertension (RH).
Methods and results
Ambulatory blood pressure (BP) and active MMP-9 (measured by zymography and ELISA) were measured at baseline, and patients were classified as having pseudo-RH or RH. Patients with RH received spironolactone and the response was determined after 8 weeks by ambulatory BP monitoring: those who achieved BP goals were considered controlled (CRH) and those who did not were considered uncontrolled (UCRH). Plasma active MMP-9 was significantly higher in patients with RH than with pseudo-RH, and correlated with 24-hour systolic BP and PP. Receiver operating characteristic analysis indicated that active MMP-9 could predict the response to spironolactone, and its combination with 24-hour PP and pulse wave velocity significantly improved this prediction. Moreover, plasma of patients with UCRH induced the MMP-9 expression pathway.
Conclusion
We propose active MMP-9 as a useful biomarker to identify patients with RH who will not respond to spironolactone. Combining MMP-9 activity with classical arterial stiffness parameters improves the prediction of the clinical response to spironolactone and might contribute to guide the most appropriate therapeutic decisions for patients with RH.

© Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2020. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 13 Jul 2020; epub ahead of print
Rodríguez-Sánchez E, Navarro-García JA, Aceves-Ripoll J, González-Lafuente L, ... Ruilope LM, Ruiz-Hurtado G
Eur Heart J Cardiovasc Pharmacother: 13 Jul 2020; epub ahead of print | PMID: 32663251
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Impact:
Abstract

2019 ESC/EAS Guidelines for management of dyslipidaemia: strengths and limitations.

Zeitouni M, Sabouret P, Kerneis M, Silvain J, ... Bruckert E, Montalescot G
In 2019, the European Society of Cardiology and European Atherosclerosis Society released a new guideline document with substantial changes regarding the assessment of cardiovascular risk and treatments. The update of high-risk criteria and categories led to a better detection and primary prevention of patients at risk of a first cardiovascular event. Nonetheless, additional efforts are needed for a better inclusion of risk modifiers, especially specific to women, to improve risk stratification and direct primary prevention. Eventually, we discuss how these new guidelines implement PCSK9 inhibitors for very-high risk individuals and the evidence supporting new LDL-C goals below such as 55 mg/dL and 40 mg/dL.

© Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2020. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 10 Jul 2020; epub ahead of print
Zeitouni M, Sabouret P, Kerneis M, Silvain J, ... Bruckert E, Montalescot G
Eur Heart J Cardiovasc Pharmacother: 10 Jul 2020; epub ahead of print | PMID: 32652000
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Impact:
Abstract

Cost-utility of ticagrelor plus aspirin in diabetic patients with stable coronary artery disease.

Wu B, Shi L
Aims
Ticagrelor plus aspirin could reduce the risks of major adverse cardiac events in diabetic patients with stable coronary artery disease (SCD), and yet it also increases bleeding risk. This study would compare the cost and effectiveness of aspirin and ticagrelor plus aspirin therapies in diabetic patients with SCD from a US health care sector perspective.
Methods and results
A state-transition Markov model was developed to project probabilities of MI, IS, bleeding and death with and without ticagrelor among all diabetic patients with SCD as the overall population, and those with a history of previous percutaneous coronary intervention (PCI) as a sub-population. Model inputs were extracted from published sources. Lifetime costs and quality-adjusted life-years (QALYs) were measured. The clinical benefits and bleeding risk of ticagrelor added to aspirin were translated into additional 0.08 QALYs at incremental costs of $19,580 in the overall population, yielding an incremental cost-utility ratio (ICUR) of $260,032/QALY. In the sub-population with an additional 0.43 QALYs at an incremental cost of $20,189, the ICUR was $46,426/QALY. Two-way sensitivity showed the clinical benefits of ticagrelor plus aspirin was counterbalanced by its risk of major bleeding. One-way sensitivity and probabilistic sensitivity analysis demonstrated the results were generally robust except the all-cause death reduction.
Conclusions
The results indicated that ticagrelor plus aspirin is likely to be a cost-effective option in the diabetic patients with a history of PCI. Diabetes management can be improved by carefully prescribing ticagrelor to individuals with low risk of bleeding and high risk of ischemic events.

© Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2020. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 08 Jul 2020; epub ahead of print
Wu B, Shi L
Eur Heart J Cardiovasc Pharmacother: 08 Jul 2020; epub ahead of print | PMID: 32645147
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Impact:
Abstract

Differential effects of dual antiplatelet therapy in patients presented with acute coronary syndrome vs. stable ischaemic heart disease after coronary artery bypass grafting.

Choi KH, Song YB, Jeong DS, Jang YH, ... Gwon HC, Lee YT
Aims
The current study sought to evaluate whether long-term clinical outcomes according to the use of dual antiplatelet therapy (DAPT) or single antiplatelet therapy (SAPT) differed between acute coronary syndrome (ACS) and stable ischaemic heart disease (SIHD) patients who underwent coronary artery bypass grafting surgery (CABG).
Methods and results
Between January 2001 and December 2017, 3199 patients with ACS (55.3%) and 2583 with SIHD (44.7%) who underwent isolated CABG were enrolled. The study population was stratified using DAPT or SAPT in ACS patients and SIHD patients. The primary outcome was a cardiovascular death or myocardial infarction (MI) at 5 years. After CABG, DAPT was more frequently used in patients with ACS than in those with SIHD [n = 1960 (61.3%) vs. n = 1313 (50.8%), P < 0.001]. Among patients with ACS, the DAPT group showed a significantly lower risk of cardiovascular death or MI at 5 years than the SAPT group [DAPT vs. SAPT, 4.0% vs. 7.8%, hazard ratio (HR) 0.521, 95% confidence interval (CI) 0.339-0.799; P = 0.003]. In contrast, among patients with SIHD, there was no significant difference in the rate of cardiovascular death or MI at 5 years between the use of DAPT and SAPT (4.0% vs. 4.0%, HR 0.991, 95% CI 0.604-1.626; P = 0.971). These findings were robust to multiple sensitivity analyses and competing risk analysis. In the subgroup analysis, the use of DAPT was associated with a significantly lower risk of cardiovascular death or MI among SIHD patients with a previous percutaneous coronary intervention (PCI), with a significant interaction between the use of DAPT and PCI history (interaction P = 0.011).
Conclusion
Among ACS patients who underwent CABG, the use of DAPT was associated with lower cardiovascular death or MI than the use of SAPT, but this was not the case in SIHD patients.
Trial registration
ClinicalTrials.gov, NCT03870815.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 05 Jul 2020; epub ahead of print
Choi KH, Song YB, Jeong DS, Jang YH, ... Gwon HC, Lee YT
Eur Heart J Cardiovasc Pharmacother: 05 Jul 2020; epub ahead of print | PMID: 33075126
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Impact:
Abstract

Early glycemic changes after initiation of oral anti-diabetic medication and risk of major adverse cardiovascular events: results from a large primary care population of patients with type 2 diabetes.

Ghouse J, Blanche P, Skov MW, Lind B, ... Holst AG, Nielsen JB
Aims
To determine the risk of major cardiovascular events (MACE) and death, associated with an early large and rapid decline in HbA1C following first time initiation of an oral antidiabetic drug (OAD).
Methods and results
We included 10,518 primary care patients with T2D, who initiated an OAD for the first time. For each individual, we measured a decline in HbA1C, as the difference between the pre-treatment HbA1C (within 3 months before OAD initiation) and the post-treatment HbA1C (within 1.5-4.5 months after OAD initiation), divided by the time between the two measurements. The decline was reported in mmol/mol change per 3 months in HbA1C and categorized by the median decline into levels of steep (≥ 9 mmol/mol [≥ 0.8%]) and flat decline (< 9 mmol/mol per 3 mo. [< 0.8%]). Pre-treatment HbA1C was categorized by the median, into levels of low (48-62 mmol/mol) and high (> 62 mmol/mol). Multiple Cox regression was used to study the effect of decline (steep vs. flat) on the outcome hazard rates separately for patients with low and high pre-treatment HbA1C. Analyses were adjusted for age, sex, traditional cardiovascular risk factors, severe comorbidities, and concomitant medication treatment. During a median follow-up time of 7.7 years, 1,625 developed MACE and 2,323 died. We found that a steep decline vs. a flat decline was significantly associated with a decreased hazard for MACE, both in individuals with high (HR 0.81; 95% CI 0.69-0.94; P = 0.005) and low pre-treatment HbA1C (HR 0.79; 95% CI 0.66-0.96; P = 0.015). The hazard of MACE was more pronounced on the short-term vs. long-term in individuals with high pre-treatment HbA1C. We found no significant association between combinations of pre-treatment HbA1C and decline categories and hazard of all-cause mortality. However, a combination of a low pre-treatment HbA1C and steep decline was associated with increased 1-year mortality (HR 1.52; 95% CI 1.00-2.29; P = 0.048) and hypoglycemia (HR 1.82; 95% CI 1.11-2.98; P = 0.017).
Conclusion
A combination of a high pre-treatment HbA1C and a steep decline in HbA1C was associated with a decreased short-term risk of MACE. A low pre-treatment HbA1C and a steep decline was associated with a long-term reduced risk of MACE, but a short-term increased risk of death and hypoglycaemia.

© Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2020. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 01 Jul 2020; epub ahead of print
Ghouse J, Blanche P, Skov MW, Lind B, ... Holst AG, Nielsen JB
Eur Heart J Cardiovasc Pharmacother: 01 Jul 2020; epub ahead of print | PMID: 32614428
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Impact:
Abstract

Effect of atorvastatin on muscle symptoms in coronary heart disease patients with self-perceived statin muscle side-effects: a randomized, double blinded crossover trial.

Kristiansen O, Vethe NT, Peersen K, Fagerland MW, ... Otterstad JE, Munkhaugen J
Aims
To estimate the effect of atorvastatin on muscle symptom intensity in coronary heart disease (CHD) patients with self-perceived statin-associated muscle symptoms (SAMS) and to determine the relationship to blood levels of atorvastatin and/or metabolites.
Methods and results
A randomized multi-center trial consecutively identified 982 patients with previous or ongoing atorvastatin treatment after a CHD event. Of these, 97 (9.9%) reported SAMS and 77 were randomized to 7-weeks double-blinded treatment with atorvastatin 40 mg/day and placebo in a crossover design. The primary outcome was the individual mean difference in muscle symptom intensity between the treatment periods, measured by visual-analogue scale (VAS) scores. Atorvastatin did not affect the intensity of muscle symptoms among 71 patients who completed the trial. Mean VAS difference [statin-placebo] was 0.31 (95% CI -0.24-0.86). The proportion with more muscle symptoms during placebo than atorvastatin was 17% (n = 12), 55% (n = 39) had the same muscle symptom intensity during both treatment periods whereas 28% (n = 20) had more symptoms during atorvastatin than placebo (confirmed SAMS). There were no differences in clinical or pharmacogenetic characteristics between these groups. The levels of atorvastatin and/or metabolites did not correlate to muscle symptom intensity among patients with confirmed SAMS (Spearmans rho ≤0.40, for all variables).
Conclusion
Re-challenge with high-intensity atorvastatin did not affect the intensity of muscle symptoms in CHD patients with self-perceived SAMS during previous atorvastatin therapy. There was no relationship between muscle symptoms and the systemic exposure to atorvastatin and/or its metabolites. The findings encourage an informed discussion to elucidate other causes of muscle complaints and continued statin use.

© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J Cardiovasc Pharmacother: 30 Jun 2020; epub ahead of print
Kristiansen O, Vethe NT, Peersen K, Fagerland MW, ... Otterstad JE, Munkhaugen J
Eur Heart J Cardiovasc Pharmacother: 30 Jun 2020; epub ahead of print | PMID: 32609361
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Impact:
Abstract

Adherence to prescribed medications in patients with heart failure - insights from liquid chromatography-tandem mass spectrometry-based urine analysis.

Simpson J, Jackson CE, Haig C, Jhund PS, ... Squire IB, Gupta P
Aims
None of the existing studies on adherence have directly measured levels of medications (or their metabolites) in patients with heart failure.
Methods and results
We used liquid chromatography-tandem mass spectrometry to measure the presence of prescribed drugs (diuretics, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers and mineralocorticoid receptor antagonists) in the urine of patients reviewed 4 to 6 weeks after hospitalisation with heart failure. Patients were unaware that adherence was being assessed. Of the 341 patients studied, 281 (82.4%) were adherent i.e. had all prescribed drugs of interest detectable in their urine. Conversely, 60 patients (17.6%) were partially or completely non-adherent. Notably, 24 of the 60 were non-adherent to only diuretic therapy and only 7 out of all 341 patients studied (2.1%) were completely non-adherent to all prescribed heart failure drugs. There were no major differences in baseline characteristics between adherent and non-adherent patients.
Conclusion
Non-adherence, assessed using a single spot urine measurement of drug levels, was confirmed in 1 of 5 patients evaluated 4 to 6 weeks after hospitalisation with heart failure.

© Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2020. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 28 Jun 2020; epub ahead of print
Simpson J, Jackson CE, Haig C, Jhund PS, ... Squire IB, Gupta P
Eur Heart J Cardiovasc Pharmacother: 28 Jun 2020; epub ahead of print | PMID: 32597982
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Impact:
Abstract

Prescriber responsibility, predictors for initiation, and 20-year trends in use of non-aspirin non-steroidal anti-inflammatory drugs in patients with cardiovascular contraindications: a nationwide cohort study.

Schmidt M, Pottegård A
Aims
To examine whether prescription patterns complied with recommendations not to use nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with cardiovascular contraindications. Moreover, we examined predictors for initiation and prescriber responsibility.
Methods and results
We identified first-time cardiovascular diseases from medical databases (1996-2017). We assessed standardized prevalence proportions, predictors from logistic regression, and prescriber identifiers. 1-year prevalence of NSAID initiation increased 3.4% from 1996 (19.4%) to 2001 (22.7%) and declined by 2.7% thereafter until 2017 (13.5%). Trends were independent of age, sex, and disease subtype, although larger annual declines occurred for heart failure (3.9%) and ischemic heart disease (3.5%) since 2002. One-year prevalence remained highest among patients with venous thromboembolism (16.6%) and angina (13.8%), and lowest for ST-segment elevation myocardial infarction (7.0%) and heart failure (8.8%). Initiators were predominantly prescribed ibuprofen (59%), diclofenac (23%) and etodolac (6%). Diclofenac and coxib use declined, while ibuprofen and naproxen use increased. Median prescribed pill dose of ibuprofen declined after 2008 from moderate/high (600 mg) to low (400 mg). Treatment duration declined for all NSAIDs, except celecoxib. Rheumatic, obesity, and pain-related conditions predicted NSAID initiation. General practitioners issued 86-91% of all NSAID prescriptions, followed by hospital prescribers (7.3-12%).
Conclusions
Initiation of NSAIDs in patients with cardiovascular disease declined since 2002. Shorter treatment duration, declining COX-2 inhibition, and increasing use of naproxen and low-dose ibuprofen suggest adherence to guidelines when NSAIDs cannot be avoided. Still, NSAID use remained prevalent despite cardiovascular contraindications, warranting awareness of appropriateness of use among general practitioners in particular.

© Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2020. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 24 Jun 2020; epub ahead of print
Schmidt M, Pottegård A
Eur Heart J Cardiovasc Pharmacother: 24 Jun 2020; epub ahead of print | PMID: 32584988
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Impact:
Abstract

Risk of infections in patients treated with ticagrelor versus clopidogrel: a systematic review and meta-analysis.

Long H, Feng Q, Tsoi MF, Fei Y, Cheung BMY
Aims
Ticagrelor has been shown to reduce the risk of pneumonia and improve lung function, but the findings across studies were inconsistent. The objective is to investigate the relative safety of ticagrelor versus clopidogrel on infection outcomes in patients with cardiovascular diseases.
Methods and results
We searched MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials.gov up to 15 October 2019. Randomized controlled trials comparing ticagrelor and clopidogrel that reported infection outcomes were included. The primary outcome was pneumonia. Secondary outcomes were upper respiratory tract infection (URTI), urinary tract infection (UTI) and sepsis. Study quality was assessed using the Cochrane Risk of Bias tool. Study selection, data extraction and quality assessment were conducted by independent authors. Random-effects model was used for data synthesis. Relative risks (RRs) and 95% confidence intervals (CIs) were pooled with a random-effects model. Out of 5231 citations, ten trials with altogether 37514 patients were included. Ticagrelor was associated with a lower risk of pneumonia (RR 0.80, 95% CI 0.67 to 0.95) compared to clopidogrel. There were no statistically significant differences for URTI (RR 0.71, 95% CI 0.34 to 1.48), UTI (RR 1.06, 95% CI 0.73 to 1.64), or sepsis (RR 0.79, 95% CI 0.50 to 1.26).
Conclusions
Compared to clopidogrel, ticagrelor reduces the risk of pneumonia, but not URTI, UTI or sepsis. Our study provides further evidence for recommending ticagrelor to patients with acute coronary syndrome at risk of pneumonia, although the mechanism by which ticagrelor reduces the risk of pneumonia merits further research.

© Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2020. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 21 Jun 2020; epub ahead of print
Long H, Feng Q, Tsoi MF, Fei Y, Cheung BMY
Eur Heart J Cardiovasc Pharmacother: 21 Jun 2020; epub ahead of print | PMID: 32569384
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Abstract

Efficacy and safety of direct oral anticoagulants versus low molecular weight heparin for cancer related venous thromboembolism: A meta-analysis of randomized trials.

Elbadawi A, Shnoda M, Mahmoud K, Elgendy IY
Aims
To examine the efficacy and safety of direct oral anticoagulants (DOAC) versus low molecular weight heparin (LMWH) in patients with cancer-related venous thrombo-embolism (VTE).
Methods and results
An electronic search of MEDLINE, SCOPUS and COCHRANE without language restrictions was performed through April 2020 for randomized controlled trials that compared the effects of DOACs versus LMWH on patients with cancer-related VTE. Summary estimates were reported using random effects model. The main efficacy outcome was VTE recurrence while the main safety outcome was major bleeding events. The final analysis included 4 randomized trials with a total of 2,907 patients. The weighted mean follow-up was 6.1 months. Compared with LMWH, DOACs were associated with lower risk of VTE recurrence (5.7% vs. 9.1%, risk ratio [RR] 0.62; 95% confidence interval [CI] 0.44 to 0.87; P = 0.01), driven by lower deep venous thrombosis (P = 0.02). There was no difference between DOACs and LMWH in major bleeding events (4.8% vs. 3.6%, RR 1.33; 95% CI 0.84 to 2.11; P = 0.23). The incidence of all-cause mortality was similar (RR 0.99; 95% CI 0.84 to 1.16; P = 0.91). Subgroup analysis suggested no differences according to the type of DOAC in recurrent VTE or major bleeding (Pinteraction= 0.53 and Pinteraction= 0.11, respectively).
Conclusion
Among patients with cancer-related VTE, DOACs were associated with lower risk of VTE recurrence and similar risk of major bleeding compared with LMWH. Future studies examining the subset of cancer patients who drive the most benefit are encouraged.

© Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2020. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 17 Jun 2020; epub ahead of print
Elbadawi A, Shnoda M, Mahmoud K, Elgendy IY
Eur Heart J Cardiovasc Pharmacother: 17 Jun 2020; epub ahead of print | PMID: 32556105
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Abstract

P2Y12 inhibitors monotherapy after short course of dual antiplatelet therapy in patients undergoing percutaneous coronary intervention: a meta-analysis of randomized clinical trials including 29 089 patients.

Bianco M, Careggio A, Destefanis P, Luciano A, ... Varbella F, Cerrato E
Aims
Dual antiplatelet therapy (DAPT) reduces the incidence of thrombotic complications at the cost of an increase in bleedings. New antiplatelet therapies focused on minimizing bleeding and maximizing antithrombotic effects are emerging. The aim of this study is to collect the current evidence coming from randomized controlled trials (RCTs) on early aspirin interruption after percutaneous coronary intervention (PCI) and current drug-eluting stent (DES) implantation and to perform a meta-analysis in order to evaluate the safety and efficacy of this strategy.
Methods and results
MEDLINE/PubMed was systematically screened for RCTs comparing P2Y12 inhibitors (P2Y12i) monotherapy after a maximum of 3 months of DAPT (S-DAPT) vs. DAPT for 12 months (DAPT) in patients undergoing PCI with DES. Baseline features were appraised. Major adverse cardiac and cerebrovascular events (MACCE: all causes of death, myocardial infarction, and stroke) and its single composites, stent thrombosis (ST) and Bleeding Academic Research Consortium (BARC) type 3 or 5 were considered and pooled with fixed and random-effects with inverse-variance weighting. A total of four RCTs including a total of 29 089 patients were identified. Overall, the majority of included patients suffered a stable coronary artery disease, while ST-elevation myocardial infarction was the least represented clinical presentation. Complex anatomical settings like left main intervention, bifurcations, and multi-lesions treatment were included although representing a minor part of the cases. At 1-year follow-up, MACCE rate was similar [odds ratio (OR) 0.90; 95% confidence intervals (CIs) 0.79-1.03] and any of its composites (all causes of death rate: OR 0.87; 95% CIs 0.71-1.06; myocardial infarction: OR 1.06; 95% CIs 0.90-1.26; stroke: OR 1.12; 95% CIs 0.82-1.53). Similarly, also ST rate was comparable in the two groups (OR 1.17; 95% CIs 0.83-1.64), while BARC 3 or 5 bleeding resulted significantly lower, adopting an S-DAPT strategy (OR 0.70; 95% CIs 0.58-0.86).
Conclusion
After a PCI with current DES, an S-DAPT strategy followed by a P2Y12i monotherapy was associated with a lower incidence of clinically relevant bleeding compared to 12 months DAPT, with no significant differences in terms of 1-year cardiovascular events.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 15 Jun 2020; epub ahead of print
Bianco M, Careggio A, Destefanis P, Luciano A, ... Varbella F, Cerrato E
Eur Heart J Cardiovasc Pharmacother: 15 Jun 2020; epub ahead of print | PMID: 32544220
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Abstract

Association between renin-angiotensin system inhibitors and COVID-19 complications.

Liabeuf S, Moragny J, Bennis Y, Batteux B, ... Masmoudi K, Gras-Champel V
Aims
To describe the characteristics of patients hospitalized with COVID-19 (including their long-term at-home medication use), and compare them with regard to the course of the disease. To assess the association between renin-angiotensin system inhibitors (RASIs) and disease progression and critical outcomes.
Methods and results
All consecutive hospitalized patients with laboratory-confirmed COVID-19 in a university hospital in Amiens (France) were included in this study. The primary composite endpoint was admission to an intensive care unit (ICU) or death before ICU admission. Univariable and multivariable logistic regression models were used to identify factors associated with the composite endpoint. Between 28 February 2020 and 30 March 2020, a total of 499 local patients tested positive for SARS-CoV-2. Of these, 231 were not hospitalized {males 33%; median [interquartile range (IQR)] age: 44 (32-54)}, and 268 were hospitalized [males 58%; median (IQR) age: 73 (61-84)]. A total of 116 patients met the primary endpoint: 47 died before ICU admission, and 69 were admitted to the ICU. Patients meeting the primary endpoint were more likely than patients not meeting the primary endpoint to have coronary heart disease and to have been taking RASIs; however, the two subsets of patients did not differ with regard to median age. After adjustment for other associated variables, the risk of meeting the composite endpoint was 1.73 times higher (odds ratio 1.73, 95% confidence interval 1.02-2.93) in patients treated at baseline with a RASI than in patients not treated with this drug class. This association was confirmed when the analysis was restricted to patients treated with antihypertensive agents.
Conclusions
We highlighted a potential safety signal for RASIs, the long-term use of which was independently associated with a higher risk of severe COVID-19 and a poor outcome. Due to the widespread use of this important drug class, formal proof based on clinical trials is needed to better understand the association between RASIs and complications of COVID-19.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 11 Jun 2020; epub ahead of print
Liabeuf S, Moragny J, Bennis Y, Batteux B, ... Masmoudi K, Gras-Champel V
Eur Heart J Cardiovasc Pharmacother: 11 Jun 2020; epub ahead of print | PMID: 32531040
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Abstract

Methodological Considerations for Investigating Oral Anticoagulation Persistence in Atrial Fibrillation.

Paquette M, Mbuagbaw L, Iorio A, Nieuwlaat R
Aims
Reports of long-term oral anticoagulant (OAC) therapy for atrial fibrillation (AF) reveal highly variable, and generally suboptimal estimates of medication persistence. The objective of this review is to summarize current literature and highlight important methodological considerations for interpreting persistence research and designing studies of persistence on OAC treatment.
Methods and results
We summarize differences in study methodology, setting, timing, treatment and other factors associated with reports of better or worse persistence. For example, prospective compared to retrospective study designs are associated with higher reported persistence. Similarly, patient factors such as permanent AF or high stroke risk, and treatment with non-vitamin K oral antagonists relative to vitamin K antagonists are associated with higher persistence. Persistence has also been reported to be higher in Europe compared to North America and higher when the treating physician is a general practitioner compared to a specialist.We propose a framework for assessing and designing persistence studies. This framework includes aspects of patient selection, reliability and validity of measures, persistence definitions, clinical utility of measurements, follow-up periods and analytic approaches.
Conclusions
Differences in study design, patient selection, treatments and factors such as the countries/regions where studies are conducted or the type of treating physician may help explain the variability in OAC persistence estimates. A framework is proposed to assess persistence studies. This may have utility to compare and interpret published studies as well as for planning of future studies.

© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J Cardiovasc Pharmacother: 18 May 2020; epub ahead of print
Paquette M, Mbuagbaw L, Iorio A, Nieuwlaat R
Eur Heart J Cardiovasc Pharmacother: 18 May 2020; epub ahead of print | PMID: 32428195
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This program is still in alpha version.