Renin-angiotensin-aldosterone system inhibitors and mortality in patients with hypertension hospitalized for COVID-19: a systematic review and meta-analysis

Objective: The association between renin-angiotensin-aldosterone (RAAS) inhibitors and Coronavirus diseases 2019 (COVID-19) mortality is unclear. We aimed to explore the association of RAAS inhibitors, including angiotensin-converting inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) with COVID-19 mortality in patients with hypertension. Methods: MEDLINE, SCOPUS, OVID, and Cochrane Library were searched for the period of January 1, 2020 to May 20, 2020. Studies reporting the association of RAAS inhibitors (ACEi and ARBs) and mortality in patients with hypertension, hospitalized for COVID-19 were extracted. Two reviewers independently extracted appropriate data of interest and assessed the risk of bias. All analyses were performed using random-effects models on log-transformed risk ratio estimates, and heterogeneity was quantified. Results: Data were collected on 2,065,805 individuals (mean age, 58.73 years; 53.4% male). Patients with hypertension taking RAAS inhibitors were 35% less likely to die from COVID-19 compared to patients with hypertension not taking RAAS inhibitors (pooled RR= 0.65, 95% Confidence Intervals (CI): 0.45-0.94). To explore the association of COVID-19 and specific classes of RAAS inhibitors, we conducted a subgroup analysis of ARBs and ACEi separately from studies that provided them. Pooled risk ratio estimates from ARBs and ACEi showed a lower but not significant risk of death from COVID-19 (RR=0.93, 95% CI: 0.70-1.22) and ACEi (RR=0.65, 95% CI: 0.32-1.30). Conclusions: In this meta-analysis, it was discovered that taking RAAS inhibitors, significantly decreased the risk of COVID-19 mortality in patients with hypertension. This indicates a potential protective role that RAAS-inhibitors may have in COVID-19 patients with hypertension.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThis study was not fundedAuthor DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:This is a meta-analysis and thus it is IRB exempt.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAll data is available within the manuscript.