Renin-angiotensin-system inhibitors and all-cause mortality in patients with COVID-19: a systematic review and meta-analysis of observational studies

Aims: We sought to evaluate the association of angiotensin-converting-enzyme inhibitors (ACEI) or AT1 blockers (ARB) therapy with clinical outcomes in patients with coronavirus disease 2019 (COVID-19). Methods and results: Electronic databases were searched to identify published studies that reported clinical outcomes in patients with COVID-19 who were or were not taking an ACEI/ARB. We studied all-cause mortality and/or severe disease outcomes. Fully adjusted effect estimates from individual studies were pooled using a random-effects model. In total, 34 (31 cohort-based and three case-control) studies met our eligibility criteria. Due to the inherent differences between cohort and case-control studies, we did not combine results of these studies but used them to identify the consistency of their results. The 31 cohort studies provided outcome data for 87 951 patients with COVID-19, of whom 22 383/83 963 (26.7%) were on ACEI/ARB therapy. In pooled analysis, we found no association between the use of ACEI/ARB and all-cause mortality/severe disease [relative risk: 0.94, 95% confidence interval (CI): 0.86-1.03, I-2 = 57%, P = 0.20] or occurrence of severe disease (relative risk: 0.93, 95% CI: 0.74-1.17, I-2 = 56%, P = 0.55). Analysis of three population-based case-control studies identified no significant association between ACEI/ARB (pooled odds ratio: 1.00, 95% CI: 0.81-1.23, I-2 = 0, P = 0.98) and all-cause mortality/severe disease. In 13 of the 31 cohort studies as well as in three case-control studies that reported outcomes separately for ACEI and ARB, there was no differential effect for mortality/severe disease outcomes. Conclusion: In patients with COVID-19, we found no association between ACEI/ARB treatment and mortality/severe disease. ACEI/ARB should not be discontinued, unless clinically indicated.