Journal: Eur Heart J Cardiovasc Pharmacother

Sorted by: date / impact
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
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
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
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
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
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
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
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
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
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
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
Go to: DOI | PubMed | PDF | Google Scholar |
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
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
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
Go to: DOI | PubMed | PDF | Google Scholar |
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
Go to: DOI | PubMed | PDF | Google Scholar |
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
Go to: DOI | PubMed | PDF | Google Scholar |
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
Go to: DOI | PubMed | PDF | Google Scholar |
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
Go to: DOI | PubMed | PDF | Google Scholar |
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
Go to: DOI | PubMed | PDF | Google Scholar |
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
Go to: DOI | PubMed | PDF | Google Scholar |
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
Go to: DOI | PubMed | PDF | Google Scholar |
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
Go to: DOI | PubMed | PDF | Google Scholar |
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
Go to: DOI | PubMed | PDF | Google Scholar |
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
Go to: DOI | PubMed | PDF | Google Scholar |
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
Go to: DOI | PubMed | PDF | Google Scholar |
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
Go to: DOI | PubMed | PDF | Google Scholar |
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
Go to: DOI | PubMed | PDF | Google Scholar |
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
Go to: DOI | PubMed | PDF | Google Scholar |
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
Go to: DOI | PubMed | PDF | Google Scholar |
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
Go to: DOI | PubMed | PDF | Google Scholar |
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
Go to: DOI | PubMed | PDF | Google Scholar |
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
Go to: DOI | PubMed | PDF | Google Scholar |
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.

© 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 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
Go to: DOI | PubMed | PDF | Google Scholar |
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
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:

This program is still in alpha version.