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

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.