Journal: Eur Heart J Cardiovasc Pharmacother

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Abstract

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

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

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

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

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

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

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

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

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

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

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

Real-world safety and efficacy of direct oral anticoagulants in atrial fibrillation: a network metanalysis on 605,771 patients.

Menichelli D, Del Sole F, Di Rocco A, Farcomeni A, ... Yh Lip G, 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 (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 (HR 2.0, 95% 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 2021. For permissions, please email: [email protected]

Eur Heart J Cardiovasc Pharmacother: 24 Jan 2021; epub ahead of print
Menichelli D, Del Sole F, Di Rocco A, Farcomeni A, ... Yh Lip G, Pastori D
Eur Heart J Cardiovasc Pharmacother: 24 Jan 2021; epub ahead of print | PMID: 33493255
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Abstract

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

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

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

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

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

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

Obesity and atrial fibrillation: making inroads through fat.

Javed S, Gupta D, Lip GYH

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

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

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

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

Rubboli A, Valgimigli M, Capodanno D, Lip GYH

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

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

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

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

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

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

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

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

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

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

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

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

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

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

This program is still in alpha version.