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.

COVID-19 in dialysis: clinical impact, immune response, prevention, and treatment

“…In a French nationwide study of almost 2 million hypertensive people, RAS blockers were associated with a 16-26% lower risk of hospitalization for COVID-19 compared to calcium channel blockers 116 . However, these results were not reproduced in other nationwide studies 117 . Moreover, losartan introduction did not reduce hospitalization rate in a RCT of 117 patients with mild symptomatic COVID-19 118 .…”

Renin‐Angiotensin Aldosterone System Inhibitors and COVID‐19: A Systematic Review and Meta‐Analysis Revealing Critical Bias Across a Body of Observational Research

“…Two nationwide studies, one each from France and Sweden, could be included in the meta‐analysis (Table 1 ). 163 , 201 Although the study from France also completed analyses on those using a combination of antihypertensive therapies, the meta‐analysis considered only outcomes commonly assessed in each study and, thus, included data from all French (n=1 186 987) and Swedish (n=164 655) residents with uncomplicated hypertension who used either an ACE inhibitor, ARB, calcium channel blocker, or TZD in monotherapy (Note: data for French citizens using a TZD in monotherapy were not available). Given that as‐treated data were available only in the study from Sweden, only intention‐to‐treat data were used in the meta‐analysis.…”

A randomized controlled trial of renin-angiotensin-aldosterone system inhibitor management in patients admitted in hospital with COVID-19

“…The results seen in our study may have differed from REPLACE COVID as the population enrolled in the RAAS-COVID-19 was older (71 vs 62 years of age) and had a higher proportion of people with prior ischemic heart disease (32.6% vs 12%) leading to a population at higher risk of acute heart failure. Across clinical settings, observational recent real-world population level studies of 165,355 patients in Sweden 33 and 659,180 patients in the Veteran's Affairs system in the United States 34 demonstrated that use of RAASi did not increase the risk of severe COVID-19 infection, further demonstrating the safety of RAASi in patients admitted with acute COVID-19.…”