Renin-angiotensin system blockers and susceptibility to COVID-19: a multinational open science cohort study

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Morales, D; Conover, M; You, SC; Pratt, N; Kostka, K; Duarte-Salles, T; Fernández-Bertolín, S; Aragón, M; DuVall, S; Lynch, K; ...Date
2020-06-12Publisher
Cold Spring Harbor LaboratoryUniversity of Melbourne Author/s
Zhang, LinAffiliation
Medicine Dentistry & Health SciencesMetadata
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Morales, D., Conover, M., You, S. C., Pratt, N., Kostka, K., Duarte-Salles, T., Fernández-Bertolín, S., Aragón, M., DuVall, S., Lynch, K., Falconer, T., van Bochove, K., Sung, C., Matheny, M., Lambert, C., Nyberg, F., Alshammari, T., Williams, A., Park, R. W. ,... Suchard, M. (2020). Renin-angiotensin system blockers and susceptibility to COVID-19: a multinational open science cohort study. https://doi.org/10.1101/2020.06.11.20125849.Access Status
Open AccessAbstract
<h4>Introduction</h4> 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. <h4>Methods</h4> 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) users 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. <h4>Results</h4> 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. <h4>Conclusion</h4> 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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