Key result
ACE inhibitors and ARBs are not linked to higher COVID-19 risk versus CCBs and thiazides.
Why the study?
Observational studies on the influence of ACE inhibitors and ARBs on COVID-19 infection risk lacked pre-specification, transparency, rigorous adjustment, and international generalizability with contradictory results.
Does ACE inhibitor or ARB use increase the risk of COVID-19 diagnosis or hospitalization in antihypertensive users compared to CCB or thiazide diuretic use?
Cohort (n=1,100,000)
Yes
Does ACE inhibitor or ARB use increase the risk of COVID-19 diagnosis or hospitalization in antihypertensive users compared to CCB or thiazide diuretic use?
Hazard Ratio: 0.98 (95% CI 0.84–1.14)
Absolute Event Rate: 5.6% vs 4.8%
ACE inhibitors and ARBs do not increase the risk of COVID-19 diagnosis or hospitalization compared to other antihypertensives, supporting their continued use during the pandemic.
Reassures against excess COVID-19 diagnosis risk with ACE/ARB monotherapy; leaves open confirmation in randomized trials.
INTRODUCTION: Angiotensin converting enzyme inhibitors (ACEs) and angiotensin receptor blockers (ARBs) could influence infection risk of coronavirus disease (COVID-19). Observational studies to date lack pre-specification, transparency, rigorous ascertainment adjustment and international generalizability, with contradictory results. METHODS: Using electronic health records from Spain (SIDIAP) and the United States (Columbia University Irving Medical Center and Department of Veterans Affairs), we conducted a systematic cohort study with prevalent ACE, ARB, calcium channel blocker (CCB) and thiazide diuretic (THZ) use to determine relative risk of COVID-19 diagnosis and related hospitalization outcomes. The study addressed confounding through large-scale propensity score adjustment and negative control experiments. RESULTS: Following over 1.1 million antihypertensive users identified between November 2019 and January 2020, we observed no significant difference in relative COVID-19 diagnosis risk comparing ACE/ARB vs CCB/THZ monotherapy (hazard ratio: 0.98; 95% CI 0.84 - 1.14), nor any difference for mono/combination use (1.01; 0.90 - 1.15). ACE alone and ARB alone similarly showed no relative risk difference when compared to CCB/THZ monotherapy or mono/combination use. Directly comparing ACE vs. ARB demonstrated a moderately lower risk with ACE, non-significant for monotherapy (0.85; 0.69 - 1.05) and marginally significant for mono/combination users (0.88; 0.79 - 0.99). We observed, however, no significant difference between drug- classes for COVID-19 hospitalization or pneumonia risk across all comparisons. CONCLUSION: There is no clinically significant increased risk of COVID-19 diagnosis or hospitalization with ACE or ARB use. Users should not discontinue or change their treatment to avoid COVID-19.
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Morales et al. (2020) conducted a cohort in Hypertension (n=1,100,000). ACE inhibitors and ARBs vs. Calcium channel blockers (CCBs) and thiazide diuretics (THZs) was evaluated on COVID-19 diagnosis (HR 0.98, 95% CI 0.84 - 1.14). ACE inhibitor and ARB use was not associated with a significantly increased risk of COVID-19 diagnosis compared to calcium channel blocker and thiazide diuretic use (HR 0.98).
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