Do cardiovascular drugs worsen COVID-19 outcomes?

Cardiovascular medications, such as angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blocker (ARBs) and anticoagulants, do not induce poor clinical outcomes in patients with COVID-19 and thus should not be discontinued, suggest the results of a meta-analysis.

However, routine use of therapeutic anticoagulation remains in doubt as it offers limited benefits relative to placebo or standard/prophylactic anticoagulation.

“As we wait for more evidence, we suggest that patients with COVID-19 on cardiovascular drugs should not discontinue taking them as it is very unlikely that these drugs, specifically ACEIs/ARBs, are harmful,” the researchers said.

“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,” they added.

A team of reviewers from the University of Liverpool, UK, searched more than 500 databases between 1 November 2020 and 2 October 2021 to identify randomized controlled trials (RCTs) that were published after their initial review. One reviewer extracted data, while the others verified this information for accuracy and completeness.

A total of 22,414 records were screened, yielding 24 and 21 RCTs in the qualitative and quantitative syntheses, respectively. ACEIs/ARBs and anticoagulants were the most examined drug classes, which were investigated by 10 and 11 studies, respectively.

Meta-analyses revealed no substantial effect of ACEIs/ARBs on hospitalization length (mean difference [MD], ‒0.42 day, 95 percent confidence interval [CI], ‒1.83 to 0.98; n=1,183), COVID-19 severity (risk ratio [RR], 0.90, 95 percent CI, 0.71‒1.15; n=1,661), and mortality (RR, 0.92, 95 percent CI, 0.58‒1.47; n=1,646). [Br J Clin Pharmacol 2022;88:3577-3599]

Likewise, anticoagulants showed no effect on hospitalization length (MD, ‒0.29 day, 95 percent CI, ‒1.13 to 0.56; n=1,449), COVID-19 severity (RR, 0.86, 95 percent CI, 0.70‒1.04; n=2,696), and mortality (RR, 0.93, 95 percent CI, 0.77‒1.13; n=5,689).

Other drug classes investigated were as follows: antiplatelets (aspirin, two trials), antithrombotics (sulodexide, one trial), calcium channel blockers (amlodipine, one trial), and lipid-modifying drugs (atorvastatin, one trial).

“Although our previous report included mostly observational studies (427/429, >99 percent), the conclusions that cardiovascular drugs are not associated with poor COVID-19 outcomes have been supported by the 24 RCTs that we have included in this update,” the researchers said. [Br J Clin Pharmacol 2021;87:4534-4545]

Notably, the number of studies examined in the meta-analyses were small (two for hospitalization, four for hospitalization length, two for severity, and nine for mortality), but many of these RCTs were platform-based, which made it possible to recruit many patients.

In addition, most of these RCTs were found to have a low risk of bias, which resulted in a high strength of evidence for all outcomes, except hospitalization, which was ranked as moderate.

“Cardiovascular diseases, mainly ischaemic heart disease, stroke and heart failure, were the leading causes of global mortality in 2017, accounting for approximately 17.8 million deaths,” the researchers said. [Lancet 2018;392:1736-1788]

“By contrast, the coronavirus disease 2019 (COVID-19) pandemic has killed >5.5 million people (out of approximately 335 million infected) as of 19 January 2022,” they added. [China Int J Infect Dis 2020;91:264-266; Lancet Infect Dis 2020;20:533-534]