Cardiovascular drugs and COVID-19 clinical outcomes: a systematic review and meta-analysis of randomized controlled trials

Innocent G Asiimwe; Sudeep P Pushpakom; Richard M Turner; Ruwanthi Kolamunnage-Dona; Andrea L Jorgensen; Munir Pirmohamed

doi:10.1111/bcp.15331

Cardiovascular drugs and COVID-19 clinical outcomes: a systematic review and meta-analysis of randomized controlled trials

Br J Clin Pharmacol. 2022 Aug;88(8):3577-3599. doi: 10.1111/bcp.15331. Epub 2022 Apr 25.

Authors

Innocent G Asiimwe¹, Sudeep P Pushpakom¹, Richard M Turner¹, Ruwanthi Kolamunnage-Dona², Andrea L Jorgensen², Munir Pirmohamed¹

Affiliations

¹ The Wolfson Centre for Personalised Medicine, MRC Centre for Drug Safety Science, Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.
² Department of Health Data Science, Institute of Population Health Sciences, University of Liverpool, United Kingdom Institute of Population Health Sciences, University of Liverpool, Liverpool, UK.

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 November 2020 and 2 October 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 -0.42, 95% confidence interval [CI] -1.83; 0.98 d, n = 1183), COVID-19 severity (risk ratio/RR 0.90, 95% CI 0.71; 1.15, n = 1661) or mortality (risk ratio [RR] 0.92, 95% CI 0.58; 1.47, n = 1646). Therapeutic anticoagulation also had no effect (hospitalization length mean difference -0.29, 95% CI -1.13 to 0.56 d, 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.

Keywords: COVID-19; RCTs; cardiovascular drugs; living systematic review; meta-analysis.

Publication types

Meta-Analysis
Review
Systematic Review
Research Support, Non-U.S. Gov't

MeSH terms

Angiotensin-Converting Enzyme Inhibitors / adverse effects
Antihypertensive Agents / therapeutic use
COVID-19 Drug Treatment*
Cardiovascular Agents* / adverse effects
Humans
Observational Studies as Topic
Randomized Controlled Trials as Topic

Substances

Angiotensin-Converting Enzyme Inhibitors
Antihypertensive Agents
Cardiovascular Agents