In a Recent Large Cohort Renin–Angiotensin–Aldosterone System Inhibitors Were Not Associated with Increased Risk of COVID-19 and Severe Illness

Mandana Chitsazan, M.D.
By Mandana Chitsazan, M.D. on

Medications acting on the renin-angiotensin-aldosterone system (RAAS), such as ACE inhibitors and angiotensin receptor blockers, did not increase the likelihood of a positive test for Covid-19 or the severity of the Covid-19. A cohort study of more than 12,500 patients conducted in a large health network in New York City, led by Dr. Reynolds, revealed. The findings of the study were recently published in the New England Journal of Medicine.

It is known that Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19), enters the respiratory epithelial cells by interacting with angiotensin-converting enzyme 2 (ACE2) receptors on the cell membrane. ACE2 is part of the renin-angiotensin-aldosterone system (RAAS). Medications that inhibit the RAAS increase the expression of ACE2 at the cell membranes. Therefore, there is a concern that the use of these medications might increase the susceptibility of the patients to contract Covid-19 and even the severity of Covid-19.

In this relatively large cohort of patients, Reynolds and colleagues evaluated the association between the use of five common antihypertensive medications and the likelihood of a positive Covid-19 and the severity of Covid-19 between March 1 and April 15, 2020, in the NYU Langone Health System. Of 12,594 patients who were included in this study, 5894 patients (46.8%) tested positive for Covid-19; 1002 of these patients (17.0%) had severe illness defined as admission to the intensive care unit (ICU), the use of invasive or noninvasive mechanical ventilation, or death. Overall, 34.6% had a history of hypertension (4357 patients). Among hypertensive patients, 2573 (59.1%) had a positive test for Covid-19, and 634 of them (24.6%) were severely ill.

In a propensity-matched analysis of hypertensive patients, there was no association between any medication class (ACE inhibitors, ARBs, beta-blockers, calcium-channel blockers, and thiazide diuretics) and an increased likelihood of a positive test result for Covid-19. None of these medications was associated with an increased risk of severe illness among patients.

There are several caveats to consider when interpreting the results of this study, as stated by the authors. Variations in the diagnostic characteristics for the Covid-19 testing methods might have led to misclassification of Covid-19 status. The study might have overestimated the severe Covid-19 cases, as many patients with mild disease who are not hospitalized might not seek medical attention and therefore, not teste for Covid-19.  The socioeconomic status, insurance, or health care access was not accounted for in propensity scores. Also, there might be additional, unmeasured confounders affecting the results which are not included in the propensity-score matching.

Despite these limitations that are inevitable in observational studies, these findings were consistent with other recent observational studies in supporting no association of ACE inhibitors and ARBs with the risk and severity of Covid-19.

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