Renin-angiotensin system blockers and susceptibility to COVID-19: a multinational open science cohort study
Daniel R. Morales,
Mitchell M Conover,
Seng Chan You,
Talita Duarte Salles,
Sergio Fernandez Bertolin,
Kees van Bochove,
Michael E Matheny,
Christophe G. Lambert,
Thamir M AlShammari,
Andrew E Williams,
Rae Woong Park,
Anthony G. Sena,
Martijn J Schuemie,
Peter R. Rijnbeek,
Ross D. Williams,
Jennifer C. E. Lane,
Albert Prats Uribe,
Daniel Prieto Alhambra,
Patrick B. Ryan,
George M Hripcsak,
Marc A Suchard
Posted 12 Jun 2020
medRxiv DOI: 10.1101/2020.06.11.20125849
Posted 12 Jun 2020
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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