The Effect of Renin-angiotensin-aldosterone System Inhibitors in Patients with Hypertension and COVID-19: A Meta-analysis of Randomized Controlled Trials and Propensity Score-matched Studies

Background: High-quality evidence for whether the use of renin-angiotensin-aldosterone system (RAAS) inhibitors worsens clinical outcomes for patients with coronavirus disease 2019 (COVID-19) is lacking. The present study aimed to evaluate the effect of RAAS inhibitors on disease severity and mortality in patients with hypertension and COVID-19 using randomized controlled trials (RCTs) and propensity score-matched (PSM) studies.

Methods: A literature search was conducted with PubMed, Embase, and Scopus databases from 31 December 2019 to 10 January 2022. We included RCTs and PSM studies comparing the risk of severe illness or mortality in patients with hypertension and COVID-19 treated or not treated with RAAS inhibitors. Individual trial data were combined to estimate the pooled odds ratio (OR) with a random-effects model.

Results: A total of 17 studies (4 RCTs and 13 PSM studies) were included in the meta-analysis. The use of RAAS inhibitors was not associated with an increased risk of severe illness (OR=1.00, 95% confidence interval [CI]: 0.88-1.14, I=28%) or mortality (OR=0.96, 95% CI: 0.83-1.11, I=16%) for patients with hypertension and COVID-19. Furthermore, there was no significant difference in the severity of COVID-19 when patients continued or discontinued treatment with RAAS inhibitors (OR=1.01, 95% CI: 0.78-1.29, I=0%).

Conclusions: This study suggests that there was no association between treatment with RAAS inhibitors and worsened COVID-19 disease outcomes. Our findings support the current guidelines that RAAS inhibitors should be continued in the setting of the COVID-19 pandemic. However, the benefit of RAAS inhibitor medications for COVID-19 patients should be further validated with more RCTs.