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Cardiovascular drugs and COVID-19 clinical outcomes: a systematic review and meta-analysis of randomized controlled trials
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  • Innocent Asiimwe,
  • Sudeep Pushpakom,
  • Richard Turner,
  • Ruwanthi Kolamunnage-Dona,
  • Andrea L. Jorgensen,
  • Munir Pirmohamed
Innocent Asiimwe
University of Liverpool

Corresponding Author:i.asiimwe@liverpool.ac.uk

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Sudeep Pushpakom
University of Liverpool Faculty of Health and Life Sciences
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Richard Turner
University of Liverpool
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Ruwanthi Kolamunnage-Dona
University of Liverpool
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Andrea L. Jorgensen
University of Liverpool Faculty of Health and Life Sciences
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Munir Pirmohamed
University of Liverpool Institute of Translational Medicine
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Abstract

Aims: To update our previously reported systematic review and meta-analysis of observational studies on cardiovascular drug exposure and COVID-19 clinical outcomes by focusing on newly published randomized controlled trials (RCTs). Methods: More than 500 databases were searched between 1-Nov-2020 and 2-Oct-2021 to identify RCTs that were published after our baseline review. One reviewer extracted data with other reviewers verifying the extracted data for accuracy and completeness. Results: After screening 22,414 records, we included 24 and 21 RCTs in the qualitative and quantitative syntheses, respectively. The most investigated drug classes were angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blocker (ARBs) and anticoagulants, investigated by 10 and 11 studies respectively. In meta-analyses, ACEI/ARBs did not affect hospitalization length (mean difference/MD -0.42, 95% CI -1.83; 0.98 days, n=1183), COVID-19 severity (risk ratio/RR 0.90, 95% CI 0.71; 1.15, n=1661) and mortality (RR 0.92, 95% CI 0.58; 1.47, n=1646). Therapeutic anticoagulation also had no effect (hospitalization length MD -0.29, 95% CI -1.13 to 0.56 days, n=1449; severity RR 0.86, 95% CI 0.70;1.04, n=2696; and, mortality RR 0.93, 95% CI 0.77;1.13, n=5689). Other investigated drug classes were antiplatelets (aspirin, 2 trials), antithrombotics (sulodexide, 1 trial), calcium channel blockers (amlodipine, 1 trial) and lipid modifying drugs (atorvastatin, 1 trial). Conclusion: Moderate- to high-certainty RCT evidence suggests that cardiovascular drugs such as ACEIs/ARBs are not associated with poor COVID-19 outcomes, and should therefore not be discontinued. These cardiovascular drugs should also not be initiated to treat or prevent COVID-19 unless they are needed for an underlying currently approved therapeutic indication.
21 Jan 2022Submitted to British Journal of Clinical Pharmacology
22 Jan 2022Submission Checks Completed
22 Jan 2022Assigned to Editor
08 Feb 2022Reviewer(s) Assigned
19 Feb 2022Review(s) Completed, Editorial Evaluation Pending
01 Mar 2022Editorial Decision: Revise Major
07 Mar 20221st Revision Received
08 Mar 2022Submission Checks Completed
08 Mar 2022Assigned to Editor
08 Mar 2022Review(s) Completed, Editorial Evaluation Pending
19 Mar 2022Editorial Decision: Accept
Aug 2022Published in British Journal of Clinical Pharmacology volume 88 issue 8 on pages 3577-3599. 10.1111/bcp.15331