No Increase in COVID-19 Risks With ACE/ARB Use

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Among patients with hypertension, previous treatment with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARBs) does not increase the risk of severe or fatal COVID-19, concludes a study in The Journal of the American Medical Association.

The retrospective analysis included data on 4480 patients with COVID-19, median age 54.7 years, drawn from Danish national registries. Patients were followed up from diagnosis until they reached a study outcome, or until early May 2020.

Twenty percent of patients had been using ACEI/ARBs, based on prescription fills within the previous 6 months. The primary outcome was death; secondary outcome was a composite of death or severe COVID-19, defined as severe acute respiratory syndrome or ICU admission.

COVID-19 patients with a history of ACEI/ARB use were older (mean age 72.8 versus 50.1 years) and more likely to be men (55.1% versus 46.1%), compared to non-ACEI/ARB users. The ACEI/ARB users also had higher rates of comorbid cardiovascular disease, including previous myocardial infarction and heart failure. About half of patients (49.6%) were hospitalized at the time of COVID-19 diagnosis.

Thirty-day mortality was 18.1% in patients with previous ACE/ARB use, compared to 7.3% in nonusers. On unadjusted analysis, mortality risk was more than twice as high in ACEI/ARB users with COVID-19, hazard ratio (HR) 2.65. However, the association became nonsignificant (HR 0.83) after adjustment for age and medical history. Standardized mortality was 8.8% in ACE/ARB users and 10.2% in nonusers.

Thirty-day rates of the composite outcome were 31.9% in ACEI/ARB users versus 14.2% in nonusers. Again, the association was not significant after adjustment for age and comorbidity. The same was true on analysis of severe COVID-19 (with 30-day rates of 22.6% and 10.4%, respectively).

A nested case-control analysis examined susceptibility in 571 COVID-19 patients with previous hypertension, compared to an age- and sex-matched group of 5710 hypertensive patients without COVID-19. Rates of ACEI/ARB use were approximately 85% in both groups.

Because angiotensin-converting enzyme 2 is the receptor for cell entry for SARS-CoV2, there have been concerns that ACE/ARB users might be more susceptible to infection, or might have worse outcomes of COVID-19. These registry data show no increase in the risk of death or severe disease in COVID-19 patients with a history or ACEI/ARB use, nor any increase in the rate of COVID-19 diagnosis associated with these widely used antihypertensive drugs.

The investigators conclude: “These findings do not support discontinuation of ACEI/ARB medications that are clinically indicated in the context of the COVID-19 pandemic” [Fosbøl EL, et al. Association of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use with COVID-19 diagnosis and mortality. JAMA. 2020; doi: 10.1001/jama.2020.11301].