Hypertension and Diabetes Drugs Not Associated with Severe COVID-19 Illness or Susceptibility

January 28, 2021

Takeaway: Findings from this rapidly expanding literature review show no indication to prophylactically stop ACEI or ARB treatment because of concerns about COVID-19. Moreover, withdrawal of long-term ACEIs or ARBs may be harmful, especially in patients with heart failure, because studies suggest that discontinuation of ACEI or ARB therapy is associated with worse outcomes.

Concerns exist that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) – medications widely used to treat hypertension and diabetes – increase susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – the viral agent that causes the disease COVID-19, and the likelihood of severe COVID-19 illness. Originally requested by the World Health Organization (WHO), this systematic review examined the relationship between ACEI or ARB use and COVID-19 illness. Literature databases including MEDLINE and the Cochrane Database of Systematic Reviews (January 2003 – May 2020), in addition to ClinicalTrials.gov and the WHO’s database of COVID-19 publications (inception – April 2020) were searched. As a “living review,” ongoing surveillance of the literature (and update of conclusions, if needed) is planned through March 2021. Ultimately, 14 observational studies involving 23,565 adults with COVID-19 from the U.S., as well as Italy, China, and the United Kingdom, were included in this review, which found:

• High-certainty evidence suggests that ACEI or ARB use is not associated with more severe COVID-19 illness, and moderate-certainty evidence suggests no association between the use of these medications and positive SARS-CoV-2 test results among symptomatic patients.

An editorial in the same issue of Annals that published the review findings states that this systematic review provides “reasonable reassurance that drugs that alter the renin-angiotensin system do not pose substantial threats as either COVID-19 risk factors or severity multipliers. Furthermore, withdrawing these drugs if they are prescribed for evidence-based indications could harm patients, especially those with heart failure.”

Impact

Investigators were able to respond to a clinical concern with potential to affect large groups of Veterans within a short timeline (i.e. months). Also, this review may have helped lower fears that these medications were harmful and prevented unintended consequences of clinicians or patients stopping them unnecessarily.

CITATION: Mackey K, King V, Gurley S, et al. Risks and impact of angiotensin-converting enzyme inhibitors of angiotensin-receptor blockers on SARS-CoV-2 infection in adults. Annals of Internal Medicine. August 2020;173:195-203.