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Renin-Angiotensin-Aldosterone System Blockers and the Risk of COVID-19

Our take —

This study adds valuable evidence that ACE inhibitors and angiostatin receptor blockers, two antihypertensive medications, are not associated with a heightened risk of COVID-19 or severe clinical illness.

Study design

Case-Control

Study population and setting

The study included as cases 6272 patients in Lombardy, Italy with laboratory-confirmed SARS-CoV-2 infection diagnosed between February 21 and March 11, 2020. 30,759 beneficiaries of the region’s public health system without diagnosed COVID-19 were used as controls, and were matched to cases by age, sex, and residency location.

Summary of Main Findings

While the use of antihypertensive medications, including ACE inhibitors and angiotensin receptor blockers (ARBs), was more common among patients with COVID-19 than among controls, this association disappeared after accounting for relevant clinical factors such as pre-existing diagnoses. COVID-19 diagnosis was not associated with either ACE inhibitor use (Odds ratio [OR]=0.96, 95% CI: 0.87,1.07) or ARB use (OR=0.95, 95% CI: 0.86,1.05). Restricting cases to those with severe clinical disease produced similar results for both ACE inhibitors (OR=0.91, 95%CI: 0.69,1.21) and ARBs (OR=0.83, 95% CI: 0.63,1.10).

Study Strengths

The study used a large sample size across many healthcare settings. Sensitivity analyses were well-conceived, accounting for uncertainty in the ascertainment of medication use.

Limitations

Given that the fundamental question is whether certain antihypertensive medications modulate the risk of severe disease, it would have been more appropriate to limit the primary analysis to those with a hypertension diagnosis. Similarly, it would likely have been more appropriate to limit the analysis of predictors of severe disease to those with a COVID-19 diagnosis. Doing so mitigates the risk of confounding by hospital presentation, health status, and more.

Value added

This study adds valuable evidence that ACE inhibitors and angiostatin receptor blockers are not associated with a heightened risk of COVID-19 or severe clinical illness.