Journal: Eur Heart J Cardiovasc Pharmacother

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Abstract

The relevance of depressive symptoms for the outcome of patients receiving vitamin K antagonists: results from the thrombEVAL cohort study.

Michal M, Eggebrecht L, Göbel S, Panova-Noeva M, ... Wild PS, Prochaska JH
Aims
Although depressive symptoms are highly prevalent in patients receiving oral anticoagulation (OAC), the relevance of depression for the outcome of anticoagulated individuals is unknown.
Methods and results
We analysed data from the multicentre cohort study thrombEVAL (NCT01809015) investigating the efficacy of OAC with vitamin K antagonists. There was an independent study monitoring, and an independent review panel assessed the endpoints. Out of n = 1558 participants, information about depressive symptoms, as measured by the two-item screener of the patient health questionnaire (PHQ-2), was available in n = 1405 individuals. The mean follow-up period was 28.04 months, with a standard deviation of 11.52 months. In multivariable Cox regression analysis, baseline PHQ-2 sum score was a strong and robust predictor of clinically relevant bleeding [hazard ratio (HR) 1.13, 95% confidence interval 1.03-1.24; P = 0.011] and all-cause mortality (HR 1.18, 1.08-1.28; P = 0.001) independent of age, sex, high school graduation, partnership, clinical profile, intake of serotonin reuptake inhibitors, and quality of OAC therapy. Individuals with clinically significant depressive symptoms (PHQ-2 ≥ 3) had a 57% increased risk for clinically relevant bleeding (fully adjusted HR 1.57, 1.08-2.28) and 54% greater risk for death (fully adjusted HR 1.54, 1.09-2.17). There was no association of depressive symptoms with thromboembolic events. For hospitalization, individuals with depressive symptoms (PHQ-2 ≥ 3) did not experience an elevated risk in the fully adjusted model (HR 1.08, 0.86-1.35; P = 0.52).
Conclusion
Assessment of depression by the PHQ-2 provided independent long-term prognostic information beyond common biomedical risk factors. These findings highlight the need for targeting depressive symptoms in the management of patients receiving OAC 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: 22 Jul 2021; 7:271-279
Michal M, Eggebrecht L, Göbel S, Panova-Noeva M, ... Wild PS, Prochaska JH
Eur Heart J Cardiovasc Pharmacother: 22 Jul 2021; 7:271-279 | PMID: 31922545
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Abstract

Identification of anticancer drugs associated with atrial fibrillation: analysis of the WHO pharmacovigilance database.

Alexandre J, Salem JE, Moslehi J, Sassier M, ... Funck-Brentano C, Dolladille C
Aims
The explosion of novel anticancer therapies has meant emergence of cardiotoxicity signals including atrial fibrillation (AF). Reliable data concerning the liability of anticancer drugs in inducing AF are scarce. Using the World Health Organization individual case safety report database, VigiBase®, we aimed to determine the association between anticancer drugs and AF.
Methods and results
A disproportionality analysis evaluating the multivariable-adjusted reporting odds ratios for AF with their 99.97% confidence intervals was performed for 176 U.S. Food and Drug Administration (FDA)- or European Medicines Agency (EMA)-labelled anticancer drugs in VigiBase®, followed by a descriptive analysis of AF cases for the anticancer drugs identified in VigiBase®. ClinicalTrial registration number: NCT03530215. A total of 11 757 AF cases associated with at least one anticancer drug were identified in VigiBase® of which 95.8% were deemed serious. Nineteen anticancer drugs were significantly associated with AF of which 14 (74%) are used in haematologic malignancies and 9 (45%) represented new AF associations not previously confirmed in literature including immunomodulating agents (lenalidomide, pomalidomide), several kinase inhibitors (nilotinib, ponatinib, midostaurin), antimetabolites (azacytidine, clofarabine), docetaxel (taxane), and obinutuzumab, an anti-CD20 monoclonal antibody.
Conclusion
Although cancer malignancy itself may generate AF, we identified 19 anticancer drugs significantly associated with a significant increase in AF over-reporting. This pharmacovigilance study provides evidence that anticancer drugs themselves could represent independent risk factors for AF development. Dedicated prospective clinical trials are now required to confirm these 19 associations. This list of suspected anticancer drugs should be known by physicians when confronted to AF in cancer patients, particularly in case of haematologic malignancies.

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: 22 Jul 2021; 7:312-320
Alexandre J, Salem JE, Moslehi J, Sassier M, ... Funck-Brentano C, Dolladille C
Eur Heart J Cardiovasc Pharmacother: 22 Jul 2021; 7:312-320 | PMID: 32353110
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Abstract

Patient-reported outcomes and medication adherence in patients with heart failure.

Rasmussen AA, Wiggers H, Jensen M, Berg SK, ... Larsen SH, Johnsen SP
Aims
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 3-year follow-up (n = 1464). 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 during follow-up. Medication non-adherence was defined as <80% of proportion of days covered. 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 3 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% confidence interval (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 1 and 3 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(s) 2020. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 22 Jul 2021; 7:287-295
Rasmussen AA, Wiggers H, Jensen M, Berg SK, ... Larsen SH, Johnsen SP
Eur Heart J Cardiovasc Pharmacother: 22 Jul 2021; 7:287-295 | PMID: 32761093
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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 all medications (or their metabolites) in patients with heart failure (HF).
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 4-6 weeks after hospitalization with HF. 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 seven out of all 341 patients studied (2.1%) were completely non-adherent to all prescribed HF 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 one of five patients evaluated 4-6 weeks after hospitalization with HF.

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: 22 Jul 2021; 7:296-301
Simpson J, Jackson CE, Haig C, Jhund PS, ... Squire IB, Gupta P
Eur Heart J Cardiovasc Pharmacother: 22 Jul 2021; 7:296-301 | PMID: 32597982
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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 low-density lipoprotein cholesterol goals below, such as 55 and 40 mg/dL.

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: 22 Jul 2021; 7:324-333
Zeitouni M, Sabouret P, Kerneis M, Silvain J, ... Bruckert E, Montalescot G
Eur Heart J Cardiovasc Pharmacother: 22 Jul 2021; 7:324-333 | PMID: 32652000
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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 (RDs), of oral factor Xa inhibitors (oFXaIs) is quite common in stroke prevention in non-valvular 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-centred 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(s) 2020. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 22 Jul 2021; 7:334-345
Bo M, Corsini A, Brunetti E, Isaia G, ... Marchionni N, De Ferrari GM
Eur Heart J Cardiovasc Pharmacother: 22 Jul 2021; 7:334-345 | PMID: 32853346
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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: 22 Jul 2021; 7:346-351
Fogacci S, Fogacci F, Favari E, Toth PP, Borghi C, Cicero AFG
Eur Heart J Cardiovasc Pharmacother: 22 Jul 2021; 7:346-351 | PMID: 33155016
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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: 22 Jul 2021; 7:352-359
De Luca L, Valgimigli M
Eur Heart J Cardiovasc Pharmacother: 22 Jul 2021; 7:352-359 | PMID: 33175148
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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: 22 Jul 2021; 7:280-286
Hamieh N, Kab S, Zins M, Blacher J, ... Melchior M, Lemogne C
Eur Heart J Cardiovasc Pharmacother: 22 Jul 2021; 7:280-286 | PMID: 33200205
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Abstract

Apixaban versus Warfarin in Patients with Left Ventricular Thrombus, A Prospective Multicenter Randomized Clinical Trial.

Alcalai R, Butnaru A, Moravsky G, Yagel O, ... Elbaz-Greener G, Leibowitz D
Aims
Current guidelines recommend anticoagulation with a vitamin K antagonist to treat left ventricular (LV) thrombus post myocardial infarction (MI). Data on the use of direct oral anticoagulants (DOACS) in this setting is limited. The aim of the study was to assess the efficacy of apixaban versus warfarin in treating LV thrombus after MI.
Methods and results
A prospective, randomized, multi-center open label clinical trial including patients with LV thrombus detected by 2D-transthoracic-echocardiography 1-14 days after acute MI. Thirty-five patients were enrolled in 3 medical centers, 17 patients were randomized to warfarin and 18 patients to apixaban. The primary outcome was the presence and size of LV thrombus 3 months after initiation of anticoagulation. Secondary outcomes were major bleeding, stroke or systemic embolism, re-hospitalization, and all-cause mortality. Mean LV thrombus size at enrollment was 18.5 × 12.3 mm in the warfarin group and 19.9 × 12.4 mm in the apixaban group (P = NS). Thirty-two patients completed 3 months follow-up. In the warfarin group two patients withdrew and in the apixaban group one patient died. Thrombus completely resolved in 14 of 15 patients in the warfarin group and in 16 of 17 in the apixaban group ((P = NS, P = 0.026 for non-inferiority). Two patients had major bleeding in the warfarin group while no major bleeding events were recorded in the apixaban group. There was one stroke in the warfarin group and one death in the apixaban group.
Conclusion
Our results suggest that apixaban is non-inferior to warfarin for treatment of patients with LV thrombus after acute MI with a 20% non-inferiority margin.

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

Eur Heart J Cardiovasc Pharmacother: 18 Jul 2021; epub ahead of print
Alcalai R, Butnaru A, Moravsky G, Yagel O, ... Elbaz-Greener G, Leibowitz D
Eur Heart J Cardiovasc Pharmacother: 18 Jul 2021; epub ahead of print | PMID: 34279598
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Abstract

Cardio-Renal Benefits of SGLT2 Inhibitors in Heart Failure with Reduced Ejection Fraction: Mechanisms and Clinical Evidence.

Aguilar-Gallardo JS, Correa A, Contreras JP
The heart and the kidneys are closely interconnected, and disease in one organ system can lead to disease in the other. This interdependence is illustrated in heart failure with reduced ejection fraction (HFrEF), where worsening heart failure can lead to renal dysfunction and vice versa. Further complicating this situation is the fact that drugs that serve as guideline directed medical therapy (GDMT) for HFrEF can affect renal function. Sodium glucose co-transporter 2 (SGLT2) inhibitors are a new class of medication with an evolving role in heart failure (HF) and chronic kidney disease (CKD). Initially found to have benefits in diabetics, new research established potential cardiovascular and renal benefits in patients with HF independent of their diabetic status and in populations with CKD. This has been established by landmark trials such as EMPEROR-Reduced, EMPA-TROPISM, CREDENCE, DAPA-CKD, DAPA-HF, and DEFINE-HF. Multiple mechanisms responsible for these benefits have been suggested by clinical and non-clinical studies, and involve cardiac and renal energetic efficiency, cardiac remodeling, preservation of renal function, immunomodulation, changes in hematocrit, and control of risk factors. As such, SGLT2 inhibitors have tremendous potential to improve outcomes in populations with HF and CKD. The purpose of this review is to discuss the current evidence and underlying mechanisms for the cardio-renal benefits of SGLT2 inhibitors in patients with HFrEF.

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

Eur Heart J Cardiovasc Pharmacother: 14 Jul 2021; epub ahead of print
Aguilar-Gallardo JS, Correa A, Contreras JP
Eur Heart J Cardiovasc Pharmacother: 14 Jul 2021; epub ahead of print | PMID: 34264341
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Abstract

Concerns about the use of digoxin in acute coronary syndromes.

Bugiardini R, Cenko E, Yoon J, van der Schaar M, ... Badimon L, Manfrini O
Aims
The use of digitalis has been plagued by controversy since its initial use. We aimed to determine the relationship between digoxin use and outcomes in hospitalized patients with acute coronary syndromes (ACSs) complicated by heart failure (HF) accounting for sex difference and prior heart diseases.
Methods and results
Of the 25,187 patients presenting with acute HF (Killip class ≥ 2) in the International Survey of Acute Coronary Syndromes (ISACS)-Archives (NCT04008173) registry, 4,722 (18.7%) received digoxin on hospital admission. The main outcome measure was all cause 30-day mortality. Estimates were evaluated by inverse probability of treatment weighting models. Women who received digoxin had a higher rate of death than women who did not receive it (33.8% vs. 29.2%; relative risk [RR] ratio:1.24;95% confidence interval [CI]: 1.12-1.37). Similar odds for mortality with digoxin were observed in men (28.5% vs. 24.9%; RR ratio 1.20; 95% CI:1.10-1.32). Comparable results were obtained in patients with no prior coronary heart disease (RR ratios:1.26; 95% CI: 1.10 to 1.45 in women and RR:1.21; 95% CI: 1.06 to 1.39 in men) and those in sinus rhythm at admission (RR ratios:1.34; 95% CI 1.15 to 1.54 in women and 1.26; 95% CI 1.10 to 1.45 in men).
Conclusion
Digoxin therapy is associated with an increased risk of early death among women and men with ACS complicated by HF. This finding highlights the need for re-examination of digoxin use in the clinical setting of ACS.

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

Eur Heart J Cardiovasc Pharmacother: 11 Jul 2021; epub ahead of print
Bugiardini R, Cenko E, Yoon J, van der Schaar M, ... Badimon L, Manfrini O
Eur Heart J Cardiovasc Pharmacother: 11 Jul 2021; epub ahead of print | PMID: 34251454
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Abstract

Cardiovascular risks associated with calcium supplementation in patients with osteoporosis: a nationwide cohort study.

Kim KJ, Kim MS, Hong N, Bae JH, ... Lee J, Kim SG
Aims
This study aimed to evaluate the real effects of calcium supplementation on cardiovascular outcomes within a population-based cohort.
Methods and results
From a nationwide health screening database in Korea, a total of 11,297 patients with osteoporosis who had taken calcium supplementation with or without vitamin D for at least 90 days (total-calcium group; calcium supplementation only [CaO], n = 567; calcium supplementation in combination with vitamin D [CaD], n = 10,730) were matched at a 1:1 ratio to patients who had not taken calcium supplements (control group) by using propensity scores. The overall mean age was 59.9 ± 8.8 years and the percentage of women was 87.9% in our study population. Over a median follow-up of 54 months, the incidence rate of composite cardiovascular diseases (CVD) per 1000 person-years was not different between the groups: 9.73 in the total-calcium group and 8.97 in the control group (adjusted hazard ratio [HR]: 1.12; 95% confidence interval [CI]: 0.99 to 1.28; P = 0.08). However, calcium supplementation without vitamin D was associated with an increased risk of composite CVD (HR: 1.54; 95% CI: 1.17 to 2.04; P < 0.01), especially non-fatal myocardial infarction (HR:1.89; 95% CI: 1.23 to 2.91; P < 0.01), compared with no calcium supplementation.
Conclusion
Our population-based study supported that taking calcium supplementation with vitamin D together did not appear to be harmful to cardiovascular health, but reminding that calcium supplementation without vitamin D should be used carefully even in populations with low dietary calcium intake.

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

Eur Heart J Cardiovasc Pharmacother: 08 Jul 2021; epub ahead of print
Kim KJ, Kim MS, Hong N, Bae JH, ... Lee J, Kim SG
Eur Heart J Cardiovasc Pharmacother: 08 Jul 2021; epub ahead of print | PMID: 34244740
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Abstract

An international audit of the management of dyslipidaemia and hypertension in patients with rheumatoid arthritis-results from 19 countries.

Rollefstad S, Ikdahl E, Wibetoe G, Sexton J, ... Medková H, Semb AG
Aims
To assess differences in estimated cardiovascular disease (CVD) risk among rheumatoid arthritis (RA) patients from different world regions. Further to evaluate the management and goal attainment of lipids and blood pressure (BP).
Methods and results
The SUrvey of CVD Risk Factors in patients with RA was conducted in 14503 patients from 19 countries during 2014-2019. The treatment goal for BP was <140/90 mmHg. CVD risk prediction and lipid goals were according to the 2016 European guidelines. Overall, 21% had a very high estimated risk of CVD, ranging from 5% in Mexico, 15% in Asia, 19% in Northern Europe, to 31% in Central and Eastern Europe and 30% in North America. Of the 52% with indication for lipid lowering treatment (LLT), 44% were using LLT. The lipid goal attainment was 45% and 18% in the high and very high-risk group, respectively. Use of statins in monotherapy was 24%, while 1% used statins in combination with other LLT. Sixty-two % had hypertension and approximately half of these patients were at BP goal. The majority of the patients used antihypertensive treatment in monotherapy (24%), while 10% and 5% as a two- or three drug combination.
Conclusion
We revealed considerable geographical differences in estimated CVD risk and preventive treatment. Low goal attainment for LLT was observed, and only half the patients obtained BP goal. Despite a high focus on the increased CVD risk in RA patients over the last decade, there is still substantial potential for improvement in CVD preventive measures.

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

Eur Heart J Cardiovasc Pharmacother: 06 Jul 2021; epub ahead of print
Rollefstad S, Ikdahl E, Wibetoe G, Sexton J, ... Medková H, Semb AG
Eur Heart J Cardiovasc Pharmacother: 06 Jul 2021; epub ahead of print | PMID: 34232315
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Abstract

Cardiovascular Outcomes with GLP-1 Receptor Agonists Versus SGLT-2 Inhibitors in Patients with Type 2 Diabetes.

Nørgaard CH, Starkopf L, Gerds TA, Vestergaard P, ... Torp-Pedersen C, Lee CJ
Aims
We examined cardiovascular outcomes associated with initiation of GLP-1RA versus SGLT-2i treatment in a real-world setting among patients with type 2 diabetes.
Methods and results
This Danish nationwide registry-based cohort study included patients with type 2 diabetes with a first ever prescription of either GLP-1RA or SGLT-2i from 2013 through 2015 with follow-up until end of 2018. All analyses were standardized with respect to age, sex, diabetes duration, comorbidity, and comedication. The main outcome was a composite of cardiovascular death, myocardial infarction, and stroke. Furthermore, the components of the composite outcome and hospitalization for heart failure were evaluated. Standardized average 3-year risks of outcomes and differences thereof were estimated using doubly robust estimation combining cause-specific Cox regression with propensity score regression. We identified 8,913 new users of GLP-1RA and 5,275 new users of SGLT-2i. The standardized 3-year risk associated with initiating GLP-1RA and SGLT-2i, respectively, was for the composite cardiovascular outcome, 5.6% (95% confidence interval (CI): 5.2-6.1) versus 5.6% (95% CI: 4.8-6.3); cardiovascular mortality, 1.6% (95% CI: 1.3-1.9) versus 1.5% (95% CI: 1.1-1.8); hospitalization for heart failure, 1.7% (95% CI: 1.5-2.0) versus 1.8% (95% CI: 1.2-2.5); myocardial infarction, 2.1% (95% CI: 1.8-2.4) versus 2.1% (95% CI: 1.5-2.6); and stroke, 2.5% (95% CI: 2.2-2.9) versus 2.6% (95% CI: 2.2-3.1).
Conclusion
In this nationwide study of patients with type 2 diabetes, initiating GLP-1RA versus SGLT-2i was not found to be associated with significant differences in cardiovascular risk.

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

Eur Heart J Cardiovasc Pharmacother: 01 Jul 2021; epub ahead of print
Nørgaard CH, Starkopf L, Gerds TA, Vestergaard P, ... Torp-Pedersen C, Lee CJ
Eur Heart J Cardiovasc Pharmacother: 01 Jul 2021; epub ahead of print | PMID: 34215881
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Abstract

Low-dose rivaroxaban plus aspirin in patients with polypharmacy and multimorbidity: an analysis from the COMPASS trial.

Vanassche T, Verhamme P, Anand SS, Shestakovska O, ... Eikelboom JW, Bosch J
Background
In patients with coronary or peripheral arterial disease, adding low dose rivaroxaban to aspirin reduces cardiovascular events and mortality. Polypharmacy and multimorbidity are frequent in such patients.
Aims
To analyze whether the benefits and risks of rivaroxaban plus aspirin varies in patients with comorbidities and receiving multiple drugs.
Methods and results
We describe ischemic events (cardiovascular death, stroke, or myocardial infarction) and major bleeding in participants from the randomised, double-blind COMPASS study by number of cardiovascular medications and concomitant medical conditions. We compared event rates and hazard ratios (HR) for rivaroxaban plus aspirin versus aspirin alone by the number of medications and concomitant conditions, and tested for interaction between polypharmacy or multimorbidity and the antithrombotic regimen.The risk of ischemic events was higher in patients with more concomitant drugs (HR 1.7, 95%CI 1.5-2.1 for >4 vs 0-2) and with more comorbidities (HR 2.3, 1.8-2.1 for >3 vs 0-1). Multimorbidity, but not polypharmacy, was associated with a higher risk of major bleeding. The relative efficacy, safety, and net clinical benefit of rivaroxaban were not affected by the number of drugs or comorbidities. Patients taking more concomitant medications derived the largest absolute reduction in the net clinical outcome with added rivaroxaban (1.1% vs 0.4% reduction with >4 vs 0-2 cardiovascular drugs, NNT 91 vs 250).
Conclusion
Adding low-dose rivaroxaban to aspirin resulted in benefits irrespective of the number of concomitant drugs or comorbidities. Multiple comorbidities and/or polypharmacy should not dissuade the addition of rivaroxaban to aspirin in otherwise eligible patients.

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

Eur Heart J Cardiovasc Pharmacother: 29 Jun 2021; epub ahead of print
Vanassche T, Verhamme P, Anand SS, Shestakovska O, ... Eikelboom JW, Bosch J
Eur Heart J Cardiovasc Pharmacother: 29 Jun 2021; epub ahead of print | PMID: 34191011
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Impact:
Abstract

Weekend versus weekday admission and clinical outcomes in heart failure patients with and without atrial fibrillation in Taiwan.

Hu WS, Lin CL
Purpose
We conduct this study to explore the associations of weekend and weekdays admission with the clinical events among heart failure (HF) patients with and without comorbid atrial fibrillation (AF).
Methods
In this study, we recruited 57919 HF patients without AF hospitalized in weekends and 57919 HF patients without AF hospitalized in weekdays. There were 21467 and 21467 HF patients with AF admisson in weekends and weekdays, respectively. The outcomes of interest included all-cause mortality, CV death (ICD-9-CM 390-459), and heart failure recurrence. Cox proportional hazard regression model was applied to estimate the hazard ratio. Variables found to be statistically significant in a univariable Cox proportional hazard regression model were further examined in a multivariable Cox proportional hazard regression model. The cumulative incidence curves were obtained by the Kaplan-Meier method and assessed by the Log-rank test.
Results
HF patients with AF and hospitalized in weekends had the highest incidence rates of rehospitalization due to HF (233.8 per1000 person-years), and CV death (23.9 per 1000 person-years) among four groups. Kaplan-Meier method shows that HF patients with AF had the higher cumulative incidence of HF recurrence than that of patients without AF.
Conclusion
HF patients with AF and hospitalized in weekends are at highest risk of HF recurrence among these four groups.

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

Eur Heart J Cardiovasc Pharmacother: 27 Jun 2021; epub ahead of print
Hu WS, Lin CL
Eur Heart J Cardiovasc Pharmacother: 27 Jun 2021; epub ahead of print | PMID: 34180528
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Impact:
Abstract

Efficacy and safety of dual pathway inhibition in patients with cardiovascular disease: a systematic review and Meta-analysis.

Galli M, Capodanno D, Benenati S, D\'Amario D, ... Andreotti F, Angiolillo DJ
Background
Low-dose direct oral anticoagulants (DOACs) in adjunct to antiplatelet therapy, known as dual pathway inhibition (DPI), have been tested to prevent ischaemic events in patients with cardiovascular disease (CVD). We conducted a systematic review and meta-analysis to determine the overall safety and efficacy of low-dose DOACs vs. placebo on a background of antiplatelet therapy.
Methods
All randomized controlled trials (RCTs) comparing low-dose DOAC (defined as a dosage below the lowest approved for stroke prevention) vs. placebo among patients with CVD receiving single or dual antiplatelet therapy in at least 50% of the population and followed for at least 6 months, were included. Incidence rate ratios (IRRs) with 95% confidence intervals (CIs) were used to overcome different follow-up durations across trials. The primary efficacy endpoint was major adverse cardiovascular events (MACE) and the primary safety endpoint major bleeding. A pre-specified subgroup analysis was performed for different DOAC-dose regimens.
Results
A total of 55,782 patients from 7 RCTs were included. Low-dose DOACs vs placebo were associated with significant reductions in MACE (IRR 0.85, 95% CI 0.78-0.91) and myocardial infarction (IRR 0.86, 95% CI 0.78-0.95) and significant increases of major (IRR 2.05, 95% CI 1.50-2.80) or all bleeding (IRR 1.82, 95% CI 1.49-2.22). CV death (IRR 0.90, 95% CI 0.79-1.03), intracranial (IRR 1.18, 95% CI 0.71-1.96) and fatal bleeding (IRR 1.13, 95% CI 0.76-1.69) did not differ significantly between strategies. Non-significant reductions of all-cause death (IRR 0.90, 95% CI 0.80-1.01) and stroke (IRR 0.73, 95% CI 0.53-1.01) favoured low-dose DOACs. Meta-regression analyses showed a significant interaction between percentage of DAPT use and increased risk of major bleeding (p = 0.04), intracranial Haemorrhage (p = 0.035) and stroke (p = 0.0003). Subgroup analysis of very low-dose DOAC, defined as ≤ 1/3 of the lowest approved dose for stroke prevention (i.e., rivaroxaban 2.5 mg twice daily) seems to mitigate the risk of bleeding without any trade-off in efficacy compared to other low-dose DOAC regimens.
Conclusions
In patients with CVD, a low-dose DOAC regimen vs. placebo, on a background of antiplatelet therapy, is effective in reducing ischaemic events at the expense of increased major and all bleeding, but without significantly increasing intracranial or fatal bleeds, while the reduction of cardiovascular and total mortality is not statistically significant. A DPI with very low-dose DOAC (i.e. rivaroxaban 2.5 mg twice daily) appears particularly advantageous, especially when combined with a single antiplatelet agent and used among patients at high ischaemic and low bleeding risk.
Study registration
This study is registered in PROSPERO (CRD42021232744).

© 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 Jun 2021; epub ahead of print
Galli M, Capodanno D, Benenati S, D'Amario D, ... Andreotti F, Angiolillo DJ
Eur Heart J Cardiovasc Pharmacother: 18 Jun 2021; epub ahead of print | PMID: 34146091
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Impact:
Abstract

Antiplatelet Therapy in Patients with Atrial Fibrillation: A Systematic Review and Metaanalysis of Randomized Trials.

Benz AP, Johansson I, Dewilde WJM, Lopes RD, ... Eikelboom JW, Connolly SJ
Aims
To systematically assess the effects of antiplatelets on clinical outcomes in patients with atrial fibrillation (AF), treated and not treated with oral anticoagulation.
Methods and results
We searched MEDLINE, Embase and CENTRAL from inception until September 2020. From 5,446 citations, we selected randomized trials allocating patients with AF to antiplatelet therapy vs. control. We applied random-effects models for meta-analysis and assessed potential effect modification with background anticoagulation use. Eighteen trials including 21,518 participants met our prespecified eligibility criteria. In 10 studies without background anticoagulation, antiplatelets reduced all-cause stroke (486/6,165 [events/patients] vs. 621/6,061; risk ratio [RR] 0.77, 95% confidence interval [CI] 0.69-0.86, I2=0%). In 8 studies with background anticoagulation, there was a signal for an increase in all-cause stroke with antiplatelets (97/4,608 vs. 72/4,684; RR 1.33, 95% CI 0.98-1.79, I2=0%), p-value for interaction < 0.001. A similar pattern emerged for ischaemic stroke. Irrespective of background anticoagulation use, antiplatelets increased major bleeding (509/10,402 vs. 328/10,496; RR 1.54, 95% CI 1.35-1.77, I2=0%) and intracranial Haemorrhage (107/10,221 vs. 65/10,232; RR 1.64, 95% CI 1.20-2.24, I2=0%), and reduced myocardial infarction (201/9,679 vs. 260/9,751; RR 0.79, 95% CI 0.65-0.94, I2=0%), all p-values for interaction ≥ 0.36. Antiplatelets did not affect mortality (1,221/10,299 vs. 1,211/10,287; RR 1.02, 95% CI 0.89-1.17, I2=29%), p-value for interaction = 0.23.
Conclusions
In patients with AF not receiving oral anticoagulation, antiplatelet therapy modestly reduced stroke. There was a corresponding signal for harm when used on top of anticoagulation. Irrespective of background anticoagulation use, antiplatelet therapy significantly increased bleeding, moderately reduced myocardial infarction and did not affect mortality.

© 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 Jun 2021; epub ahead of print
Benz AP, Johansson I, Dewilde WJM, Lopes RD, ... Eikelboom JW, Connolly SJ
Eur Heart J Cardiovasc Pharmacother: 16 Jun 2021; epub ahead of print | PMID: 34142118
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Impact:
Abstract

Impact Of Chronic Kidney Disease On The Pharmacodynamic And Pharmacokinetic Effects Of Ticagrelor In Patients With Diabetes Mellitus And Coronary Artery Disease.

Franchi F, Rollini F, Been L, Maaliki N, ... Bass TA, Angiolillo DJ
Aims
Patients with diabetes mellitus (DM) and chronic kidney disease (CKD) are at increased risk of atherothrombotic events. Ticagrelor reduces ischaemic events compared to clopidogrel, with the greatest risk reduction in patients with both DM and CKD. How CKD status affects the pharmacodynamic (PD) and pharmacokinetic (PK) profiles of different ticagrelor maintenance dose regimens in patients with DM is unknown.
Methods and results
In this randomized, cross-over study, patients with DM on treatment with dual antiplatelet therapy (aspirin and clopidogrel) were stratified according to CKD status and randomized to ticagrelor 90 mg bid or 60 mg bid. PK/PD assessments were performed at baseline, after 7-10 days of ticagrelor (peak and trough), and after 7-10 days of alternative ticagrelor regimen (peak and trough). PK assessments included plasma concentrations of ticagrelor and its major metabolite. PD assessments included VASP-PRI, VerifyNow P2Y12, and LTA.A total of 92 patients with DM (CKD, n = 44; non-CKD, n = 48) were randomized. Levels of platelet reactivity were lower with the 90 mg compared with the 60 mg ticagrelor dose, which was statistically significant in non-CKD but not in CKD patients for most PD measures. There were no significant differences in the primary endpoint (trough levels of VASP-PRI following ticagrelor 90 mg dosing) between cohorts (31 ± 20 vs 25 ± 14; p = 0.105). VerifyNow and LTA provided similar findings. PK assessments tracked PD profiles showing increased plasma concentrations of ticagrelor and its major metabolite in CKD compared to non-CKD patients.
Conclusion
In patients with DM, although ticagrelor maintenance dose regimens (60 mg and 90 mg) yield potent P2Y12 inhibition, levels of platelet reactivity tended to be higher and subject to broader variability in non-CKD compared with CKD patients.
Clinical trial registration
http://www.clinicaltrials.gov Unique Identifier: NCT02539160.

© 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: 10 Jun 2021; epub ahead of print
Franchi F, Rollini F, Been L, Maaliki N, ... Bass TA, Angiolillo DJ
Eur Heart J Cardiovasc Pharmacother: 10 Jun 2021; epub ahead of print | PMID: 34114623
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Impact:
Abstract

Outcomes after delayed primary percutaneous coronary intervention versus pharmaco-invasive strategy in ST-segment elevation myocardial infarction in Norway.

Jortveit J, Pripp AH, Halvorsen S
Aims
Primary percutaneous coronary intervention (pPCI) is the preferred reperfusion strategy in patients with ST-segment elevation myocardial infarction (STEMI) provided it can be performed within 120 min from diagnosis. However, it is unclear whether pPCI or a pharmaco-invasive (P-I) strategy is the best choice in patients who cannot receive timely pPCI. The aim of the present study was to compare outcomes after delayed and late pPCI vs. a P-I strategy in STEMI patients who did not receive timely pPCI.
Methods and results
All patients with STEMI registered in the Norwegian Myocardial Infarction Registry (NORMI) between 2013 and 2019, with ≤12 hours from symptom onset to first medical contact and available timelines were included in the study. The primary outcome was all-cause mortality, and follow-up was through 2019.A total of 21121 (27% of 78368) STEMI patients were registered in the NORMI. Among patients who met the inclusion criteria, 7238 (54%) patients underwent timely pPCI, 1537 (11%) delayed pPCI (121-180 min), 1012 (7%) late pPCI (>180 min), and 2338 (17%) patients were treated with a P-I strategy. After a median follow-up time of 2.5 years, mortality was higher in the delayed pPCI (adjusted HR 1.3, 95% CI 1.0-1.5) and in the late pPCI group (adjusted HR 1.4, 95% CI 1.1-1.7) compared to the P-I strategy group, but bleeding complications were more frequent after P-I strategy.
Conclusions
In STEMI patients who did not receive timely PCI, a P-I strategy seemed to be associated with better long-term survival compared to delayed/late pPCI.

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

Eur Heart J Cardiovasc Pharmacother: 25 May 2021; epub ahead of print
Jortveit J, Pripp AH, Halvorsen S
Eur Heart J Cardiovasc Pharmacother: 25 May 2021; epub ahead of print | PMID: 34038535
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Impact:
Abstract

Medical treatment of heart failure with reduced ejection fraction: the dawn of a new era of personalized treatment?

Ameri P, Bertero E, Maack C, Teerlink JR, Rosano G, Metra M
Recent trials have shown the efficacy of new drugs for the medical therapy of heart failure and reduced ejection fraction (HFrEF). Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduced hospitalizations for HF, HF events, and cardiovascular death in patients with HFrEF or hospitalized for HF. Iron repletion with ferric carboxymaltose (FCM) improved symptoms, functional capacity, and quality of life in chronic HFrEF patients, and decreased the risk of subsequent HF hospitalizations in subjects with acutely decompensated HF. New-generation potassium binders may allow initiation and up-titration of renin-angiotensin-aldosterone system inhibitors (RASi). Lastly, the guanylate cyclase stimulator vericiguat and the myosin activator omecamtiv mecarbil reduced the primary endpoint in two major controlled trials. These results open novel pathways for the treatment of HFrEF. This review discusses new opportunities of an individualized approach to HFrEF pharmacotherapy, where new compounds expand a spectrum of drugs that target primarily neuroendocrine activation. SGLT2i can be safely applied once daily at a fixed dose to the vast majority of patients with HFrEF, including those with moderate renal dysfunction and/or systolic blood pressure as low as 95-100 mmHg. Additional medications are suitable for more specific phenotypes, with ivabradine providing benefit in patients with sinus rhythm and heart rates ≥70 beats per minute, FCM in the presence of iron deficiency, and potassium-lowering agents to implement RASi when hyperkalaemia occurs. Vericiguat and omecamtiv mecarbil also have potential for tailored approaches towards the hemodynamic status. Thus, a new era is starting for a more personalized medical treatment of HFrEF.

© 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 May 2021; epub ahead of print
Ameri P, Bertero E, Maack C, Teerlink JR, Rosano G, Metra M
Eur Heart J Cardiovasc Pharmacother: 25 May 2021; epub ahead of print | PMID: 34037742
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Impact:
Abstract

De-escalation of antiplatelets after percutaneous coronary intervention: a Bayesian network meta-analysis of various de-escalation strategies.

Khan SU, Khan MZ, Khan MS, Mahmood A, ... Michos ED, Alkhouli M
Aims
To compare early de-escalation of dual antiplatelet therapy (DAPT) (1-3 months) to monotherapy with either P2Y12 inhibitor or aspirin vs. 12 months DAPT after percutaneous coronary intervention (PCI) with drug-eluting stent (DES).
Methods and results
Electronic databases of Medline, Embase, and Cochrane library were searched through February 2020 to identify randomized controlled trials. A Bayesian network meta-analysis was conducted with random effects model. The main endpoints of interest were cardiovascular mortality and total bleeding events. Among seven trials (35 821 patients), 52.6% patients were presented with acute coronary syndrome. A total of 3359 patients and 14 530 patients were de-escalated to aspirin and P2Y12 inhibitor monotherapy, respectively. At a median follow-up of 12 months, compared with 12 months of DAPT, there was no significant difference in cardiovascular mortality between 1-month DAPT followed by P2Y12 inhibitor monotherapy [hazard ratio (HR) 0.84 (95% credible interval 0.29-2.43)], 3 months of DAPT followed by P2Y12 inhibitor monotherapy [HR 0.74 (0.39-1.46)], or 3 months of DAPT [HR 1.00 (0.54-1.86)] followed by aspirin monotherapy. Except for de-escalation of DAPT to aspirin monotherapy after 3 months [HR 0.75 (0.43-1.20)], de-escalation to P2Y12 inhibitor monotherapy after 1 month [HR 0.28 (0.10-0.83)], or 3 months [HR 0.57 (0.33-0.98)] were associated with significant decrease in total bleeding events. There were no significant differences in terms of ischaemic endpoints among different DAPT strategies.
Conclusion
Early de-escalation of DAPT (1-3 months) to monotherapy with a P2Y12 inhibitor instead of aspirin might be a safer and equally effective approach compared with 12 months of DAPT in patients with PCI and DES.

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: 22 May 2021; 7:209-215
Khan SU, Khan MZ, Khan MS, Mahmood A, ... Michos ED, Alkhouli M
Eur Heart J Cardiovasc Pharmacother: 22 May 2021; 7:209-215 | PMID: 32271872
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Impact:
Abstract

Aspirin-omitted dual antithrombotic therapy in non-valvular atrial fibrillation patients presenting with acute coronary syndrome or undergoing percutaneous coronary intervention: results of a meta-analysis.

Luo CF, Mo P, Li GQ, Liu SM
Aims
To investigate the effects of aspirin-omitted dual antithrombotic therapy (DAT) on myocardial infarction and stent thrombosis in non-valvular atrial fibrillation (NVAF) patients presenting with acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI).
Methods and results
A systematic review and meta-analysis were performed using PubMed to search for randomized clinical trials comparing DAT with triple antithrombotic therapy (TAT) in this setting. Three trials involving 8845 patients were included (4802 and 4043 patients treated with DAT and TAT, respectively). There were no significant differences in all-cause death and stroke between the aspirin-omitted DAT group and TAT group. Otherwise, the incidence of myocardial infarction was significantly higher with aspirin-omitted DAT vs. TAT [odds ratio (OR): 1.29, 95% confidence interval (CI): 1.02-1.63; P = 0.04; I2 = 0%]. Similarly, the incidence of stent thrombosis increased in patients treated with aspirin-omitted DAT vs. TAT (OR: 1.61, 95% CI: 1.02-2.53; P = 0.04; I2 = 0%). The occurrence of major bleeding and clinically relevant non-major bleeding events, as defined by the International Society on Thrombosis and Haemostasis, was significantly lower with aspirin-omitted DAT vs. TAT (OR: 0.61, 95% CI: 0.48-0.78; P = 0.02; I2 = 76%). Similar results were found according to the International Society on Thrombosis and Haemostasis major bleeding, Thrombolysis in Myocardial Infarction major or minor bleeding, and Thrombolysis in Myocardial Infarction major bleeding scales.
Conclusion
Aspirin-omitted DAT reduces the occurrence of bleeding episodes, with a higher rate of myocardial infarction and stent thrombosis in NVAF patients presenting with ACS or undergoing 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: 22 May 2021; 7:218-224
Luo CF, Mo P, Li GQ, Liu SM
Eur Heart J Cardiovasc Pharmacother: 22 May 2021; 7:218-224 | PMID: 32129850
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Impact:
Abstract

Indirect comparison of the efficacy and safety of alirocumab and evolocumab: a systematic review and network meta-analysis.

Guedeney P, Sorrentino S, Giustino G, Chapelle C, ... Mehran R, Montalescot G
Aims
Although alirocumab and evolocumab have both been associated with improved outcomes in patients with dyslipidaemia or established atherosclerotic cardiovascular disease, data on their respective performances are scarce. This study aimed at providing an indirect comparison of the efficacy and safety of alirocumab vs. evolocumab.
Methods and results
We conducted a systematic review and network meta-analysis of randomized trials comparing alirocumab or evolocumab to placebo with consistent background lipid-lowering therapy up to November 2018. We estimated the relative risk (RR) and the 95% confidence intervals (CIs) using fixed-effect model in a frequentist pairwise and network meta-analytic approach. A total of 30 trials, enrolling 59 026 patients were included. Eligibility criteria varied significantly across trials evaluating alirocumab and evolocumab. Compared with evolocumab, alirocumab was associated with a significant reduction in all-cause death (RR 0.80, 95% CI 0.66-0.97) but not in cardiovascular death (RR 0.83, 95% CI 0.65-1.05). This study did not find any significant differences in myocardial infarction (RR 1.15, 95% CI 0.99-1.34), stroke (RR 0.96, 95% CI 0.71-1.28), or coronary revascularization (RR 1.13, 95% CI 0.99-1.29) between the two agents. Alirocumab was associated with a 27% increased risk of injection site reaction compared to evolocumab; however, no significant differences were found in terms of treatment discontinuations, systemic allergic reaction, neurocognitive events, ophthalmologic events, or new-onset of or worsening of pre-existing diabetes.
Conclusion
Alirocumab and evolocumab share a similar safety profile except for injection site reaction. No significant differences were observed across the efficacy endpoints, except for all-cause death, which may be related to the heterogeneity of the studied populations treated with the two drugs.

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: 22 May 2021; 7:225-235
Guedeney P, Sorrentino S, Giustino G, Chapelle C, ... Mehran R, Montalescot G
Eur Heart J Cardiovasc Pharmacother: 22 May 2021; 7:225-235 | PMID: 32275743
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Impact:
Abstract

Long-term prognosis of de novo atrial fibrillation during acute myocardial infarction: the impact of anti-thrombotic treatment strategies.

Hofer F, Kazem N, Hammer A, El-Hamid F, ... Niessner A, Sulzgruber P
Aims
While the prognosis of patients presenting with de novo atrial fibrillation (AF) during the acute phase of myocardial infarction has been controversially discussed, it seems intuitive that affected individuals have an increased risk for both thrombo-embolic events and mortality. However, profound data on long-term outcome of this highly vulnerable patient population are not available in current literature. Therefore, we aimed to investigate the impact of de novo AF and associated anti-thrombotic treatment strategies on the patient outcome from a long-term perspective.
Methods and results
Patients presenting with acute myocardial infarction, treated at the Medical University of Vienna, were enrolled within a clinical registry and screened for the development of de novo AF. After discharge, participants were followed prospectively over a median time of 8.6 years. Primary study endpoint was defined as cardiovascular mortality. Out of 1372 enrolled individuals 149 (10.9%) developed de novo AF during the acute phase of acute myocardial infarction. After a median follow-up time of 8.6 years, a total of 418 (30.5%) died due to cardiovascular causes, including 93 (62.4%) in the de novo AF subgroup. We found that de novo AF was significantly associated with long-term cardiovascular mortality with an adjusted HR of 1.45 (95% CI 1.19-2.57; P < 0.001). While patients with de novo AF were less likely to receive a triple anti-thrombotic therapy as compared to patients with pre-existing AF at time of discharge, this therapeutic approach showed a strong and inverse association with mortality in de novo AF, with an adj. HR of 0.86 (95% CI 0.45-0.92; P = 0.012).
Conclusion
De novo AF was independently associated with a poor prognosis with a 67% increased risk of long-term cardiovascular mortality. Intensified anti-thrombotic treatment in this high-risk patient population might be considered.

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: 22 May 2021; 7:189-195
Hofer F, Kazem N, Hammer A, El-Hamid F, ... Niessner A, Sulzgruber P
Eur Heart J Cardiovasc Pharmacother: 22 May 2021; 7:189-195 | PMID: 32289167
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Impact:
Abstract

Management of patients with combined arterial hypertension and aortic valve stenosis: a consensus document from the Council on Hypertension and Council on Valvular Heart Disease of the European Society of Cardiology, the European Association of Cardiovascular Imaging (EACVI), and the European Association of Percutaneous Cardiovascular Interventions (EAPCI).

Mancusi C, de Simone G, Brguljan Hitij J, Sudano I, ... Flachskampf FA, Gerdts E
Aortic valve stenosis (AS) is the third most common cardiovascular disease. The prevalence of both AS and arterial hypertension increases with age, and the conditions therefore often co-exist. Co-existence of AS and arterial hypertension is associated with higher global left ventricular (LV) pressure overload, more abnormal LV geometry and function, and more adverse cardiovascular outcome. Arterial hypertension may also influence grading of AS, leading to underestimation of the true AS severity. Current guidelines suggest re-assessing patients once arterial hypertension is controlled. Management of arterial hypertension in AS has historically been associated with prudence and concerns, mainly related to potential adverse consequences of drug-induced peripheral vasodilatation combined with reduced stroke volume due to the fixed LV outflow obstruction. Current evidence suggests that patients should be treated with antihypertensive drugs blocking the renin-angiotensin-aldosterone system, adding further drug classes when required, to achieve similar target blood pressure (BP) values as in hypertensive patients without AS. The introduction of transcatheter aortic valve implantation has revolutionized the management of patients with AS, but requires proper BP management during and following valve replacement. The purpose of this document is to review the recent evidence and provide practical expert advice on management of hypertension in patients with AS.

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: 22 May 2021; 7:242-250
Mancusi C, de Simone G, Brguljan Hitij J, Sudano I, ... Flachskampf FA, Gerdts E
Eur Heart J Cardiovasc Pharmacother: 22 May 2021; 7:242-250 | PMID: 32353143
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Impact:
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 with 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 with North America and higher when the treating physician is a general practitioner compared with 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: 22 May 2021; 7:251-260
Paquette M, Mbuagbaw L, Iorio A, Nieuwlaat R
Eur Heart J Cardiovasc Pharmacother: 22 May 2021; 7:251-260 | PMID: 32428195
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Impact:
Abstract

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

Li HL, 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 vs. 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, 10 trials with altogether 37 514 patients were included. Ticagrelor was associated with a lower risk of pneumonia (RR 0.80, 95% CI 0.67-0.95) compared to clopidogrel. There were no statistically significant differences for URTI (RR 0.71, 95% CI 0.34-1.48), UTI (RR 1.06, 95% CI 0.73-1.64), or sepsis (RR 0.79, 95% CI 0.50-1.26).
Conclusion
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(s) 2020. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 22 May 2021; 7:171-179
Li HL, Feng Q, Tsoi MF, Fei Y, Cheung BMY
Eur Heart J Cardiovasc Pharmacother: 22 May 2021; 7:171-179 | PMID: 32569384
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Impact:
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: 22 May 2021; 7:196-205
Bianco M, Careggio A, Destefanis P, Luciano A, ... Varbella F, Cerrato E
Eur Heart J Cardiovasc Pharmacother: 22 May 2021; 7:196-205 | PMID: 32544220
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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 with other anti-platelet agents and is a cause of drug discontinuation. We aimed to explore the contribution of central apnoeas (CA) 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 two-dimensional Doppler echocardiography, pulmonary static/dynamic testing, carbon monoxide diffusion capacity assessment, 24-h 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 two groups. Patients on ticagrelor, when compared with those on prasugrel, reported more frequently dyspnoea (43.3% vs. 6.7%, P = 0.001; severe dyspnoea 23.3% vs. 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-h period (all P < 0.001). Similarly, 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).
Conclusion
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(s) 2020. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 22 May 2021; 7:180-188
Giannoni A, Borrelli C, Gentile F, Mirizzi G, ... Emdin M, Passino C
Eur Heart J Cardiovasc Pharmacother: 22 May 2021; 7:180-188 | PMID: 32667975
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Abstract

Long-term cardiovascular outcomes after orlistat therapy in patients with obesity: a nationwide, propensity-score matched cohort study.

Ardissino M, Vincent M, Hines O, Amin R, ... Moussa O, Purkayastha S
Aims
The rising prevalence of obesity and its associated comorbidities represent a growing public health issue; in particular, obesity is known to be a major risk factor for cardiovascular disease. Despite the evidence behind the efficacy of orlistat in achieving weight loss in patients with obesity, no study thus far has quantified its long-term effect on cardiovascular outcomes. The purpose of this study is to explore long-term cardiovascular outcomes after orlistat therapy.
Methods and results
A propensity-score matched cohort study was conducted on the nation-wide electronic primary and integrated secondary healthcare records of the Clinical Practice Research Datalink (CPRD). The 36 876 patients with obesity in the CPRD database who had completed a course of orlistat during follow-up were matched on a 1:1 basis with equal numbers of controls who had not taken orlistat. Patients were followed up for a median of 6 years for the occurrence of the primary composite endpoint of major adverse cardiovascular events (fatal or non-fatal myocardial infarction or ischaemic stroke), and a number of secondary endpoints including primary endpoint components individually, the occurrence of new-onset heart failure, coronary revascularization, new chronic kidney disease stage III+ (CKD3+), and all-cause mortality. During the median study follow-up of 6 years, the occurrence of major adverse cardiovascular events was lower in the orlistat cohort [hazard ratio (HR) 0.74; 95% confidence interval (CI) 0.66-0.83, P < 0.001]. Patients who took orlistat experienced lower rates of myocardial infarction (HR 0.77; 95% CI 0.66-0.88, P < 0.001) and ischaemic stroke (HR 0.68; 95% CI 0.56 to -0.84, P < 0.001) as well as new-onset heart failure (HR 0.79; 95% CI 0.67-0.94, P = 0.007). There was no differences in revascularization rates (HR 1.12; 95% CI 0.91-1.38, P = 0.27), but a lower rate of both CKD3+ development (HR 0.78; 95% CI 0.73-0.83, P < 0.001) and mortality (HR 0.39, 95% CI 0.36 to -0.41, P < 0.001) was observed.
Conclusion
In this nation-wide, propensity-score matched study, orlistat was associated with lower rates of overall major adverse cardiovascular events, new-onset heart failure, renal failure, and mortality. This study adds to current evidence on the known improvements in cardiovascular risk factor profiles of orlistat treatment by suggesting a potential role in primary prevention.

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: 14 May 2021; epub ahead of print
Ardissino M, Vincent M, Hines O, Amin R, ... Moussa O, Purkayastha S
Eur Heart J Cardiovasc Pharmacother: 14 May 2021; epub ahead of print | PMID: 33991094
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Abstract

Statin but not Aspirin Treatment is Associated with Reduced Cardiovascular Risk in Patients with Diabetes without Obstructive Coronary Artery Disease.

Olesen KKW, Heide-Jørgensen U, Thim T, Thomsen RW, ... Sørensen HT, Maeng M
Aims
Patients with diabetes and no obstructive coronary artery disease (CAD) as assessed by coronary angiography (CAG) are frequently treated with aspirin and statins. We examined the effectiveness of aspirin and statin treatment on cardiovascular and bleeding incidence in patients with diabetes and absent obstructive CAD.
Methods and results
The study included patients with diabetes and absent obstructive CAD as assessed by CAG from 2003 to 2016 in Western Denmark. We stratified patients by aspirin and statin treatment within 6 months after CAG in two separate analyses. Outcomes were MACE (major adverse cardiovascular events, a composite of myocardial infarction, ischaemic stroke, and death) and bleeding (aspirin only). To account for confounding, we used propensity score-based weights to estimate the inverse probability of treatment-weighted hazard ratios (HRIPTW). We included 4,124 patients with diabetes but without CAD as assessed by CAG, among whom 2,474 (60%) received aspirin and 2,916 (71%) received statin treatment within 6 months following CAG. Median follow-up was 4.9 years. Aspirin did not reduce 10-year MACE (21.3% vs 21.8%, HRIPTW 1.01, 95% confidence interval (CI) 0.82-1.25), all-cause death (HRIPTW 0.96, 95% CI 0.74-1.23), or bleeding (HRIPTW 0.95, 95% CI 0.73-1.23), compared to those not receiving aspirin treatment. Statin treatment reduced MACE (25% vs. 37%, HRIPTW 0.58, 95% CI 0.48-0.70) compared to those not receiving statin treatment.
Conclusion
Among patients with diabetes and no obstructive CAD, aspirin neither reduced MACE nor increased bleeding. In contrast, statin treatment was associated with a major reduction in risk of MACE.

© 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: 13 May 2021; epub ahead of print
Olesen KKW, Heide-Jørgensen U, Thim T, Thomsen RW, ... Sørensen HT, Maeng M
Eur Heart J Cardiovasc Pharmacother: 13 May 2021; epub ahead of print | PMID: 33989394
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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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This program is still in alpha version.