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

Abstract

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.

Keywords: COVID‐19; SARS‐CoV‐2; angiotensin II receptor blocker; angiotensin‐converting enzyme inhibitor; hypertension.

Figure 1. Flowchart detailing the identification of the study population.

ACE indicates angiotensin‐converting enzyme; ARB, angiotensin II type‐I receptor blocker; CCB, calcium channel blocker; RAAS, renin‐angiotensin aldosterone system; and TZD, thiazide diuretic.

Figure 2. The Aalen‐Johansen estimate of the cumulative incidence function for death unrelated to COVID‐19 and for a combination of hospitalization or death with COVID‐19, in people on monotherapy with a renin‐angiotensin aldosterone system (RAAS) inhibitor and those on monotherapy with either a calcium channel blocker (CCB) or a thiazide diuretic (TZD).