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Background Considering the widespread risk of collider bias and confounding by indication in previous research, the associations between renin‐angiotensin aldosterone system (RAAS) inhibitor use and COVID‐19 remain unknown. Accordingly, this study tested the hypothesis that RAAS inhibitors influence the summation effect of COVID‐19 and its progression to severe outcomes. Methods and Results This nationwide cohort study compared all residents of Sweden, without prior cardiovascular disease, in monotherapy (as of January 1, 2020) with a RAAS inhibitor to those using a calcium channel blocker or a thiazide diuretic. Comparative cohorts were balanced using machine‐learning‐derived propensity score methods. Of 165 355 people in the analysis (51% women), 367 were hospitalized or died with COVID‐19 (246 using a RAAS inhibitor versus 121 using a calcium channel blocker or thiazide diuretic; Cox proportional hazard ratio [HR], 0.97; 95% CI, 0.74–1.27). When each outcome was assessed separately, 335 people were hospitalized with COVID‐19 (HR, 0.92; 95% CI, 0.70–1.22), and 64 died with COVID‐19 (HR, 1.22; 95% CI, 0.68–2.19). The severity of COVID‐19 outcomes did not differ between those using a RAAS inhibitor and those using a calcium channel blocker or thiazide diuretic (ordered logistic regression odds ratio, 1.01; 95% CI, 0.89–1.14). Conclusions Despite potential limitations, this study is among the best available evidence that RAAS inhibitor use in primary prevention does not increase the risk of severe COVID‐19 outcomes; presenting strong data from which scientists and policy makers alike can base, with greater confidence, their current position on the safety of using RAAS inhibitors during the COVID‐19 pandemic.

Renin‐Angiotensin Aldosterone System Inhibitors in Primary Prevention and COVID‐19