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Renin-Angiotensin-Aldosterone System Inhibitors and Risk of COVID-19

Our take —

In a large study from New York, patients with hypertension taking ACE inhibitors and ARBs were neither more susceptible to SARS-CoV-2 infection nor more likely to experience a severe disease once infected. In conjunction with Mancia et al. (2020), this study builds the case that these medications should not be avoided or discontinued due to COVID-19 concerns.

Study design

Retrospective cohort

Study population and setting

This investigation of COVID-19 susceptibility included 4,357 patients with hypertension who received a SARS-CoV-2 test in the NYU health system between March 1 and April 15, 2020. 2,573 patients with both a positive test and hypertension were included in the analysis of factors associated with disease severity. The authors used propensity score matching to address confounding.  An absolute difference of 10% in the likelihood of a positive test or of severe disease was pre-specified as the threshold for a “substantial difference” in risk of severe disease.

Summary of Main Findings

There were no substantial differences in the probability of testing positive for SARS-CoV-2 associated with the use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), beta-blockers, calcium-channel blockers, or thiazide diuretics. 25% of COVID-19 patients with hypertension experienced severe disease (ICU admission, mechanical ventilation, or death); however, there were no substantial differences in the probability of severe disease with the use of given antihypertensive medications. Calcium channel blockers were associated with a 4.4% increased risk of severe disease, and beta blockers with a 1.4% decreased risk, but both fell below the pre-specified significance threshold.

Study Strengths

The study employed robust statistical methods to account for a wide range of differences between patients (propensity-score matching).  Participants were followed longitudinally.

Limitations

Data on medical diagnoses and medication history were obtained from electronic medical records.  These may be unreliable, particularly for patients who do not regularly receive care in the NYU health system; this may have led to misclassification of recent medication use. Secondly, individuals who never developed symptoms were not tested; this group may differ from the study population in associations between medication use and SARS-CoV-2 prevalence or severity.  Finally, hypertensive patients not receiving any antihypertensive medications might be different from those receiving medications in ways not fully accounted for in the analyses. Sensitivity analyses excluding these patients would add valuable insight.

Value added

This is one of largest studies to date investigating the potential role of antihypertensive medications, and in particular ACE inhibitors and ARBs, in modulating the susceptibility to, and severity of, SARS-CoV-2 infection.