Association Between ACEIs or ARBs Use and Clinical Outcomes in COVID-19 Patients: A Systematic Review and Meta-analysis

ImportanceThere is a controversy regarding whether or not to continue angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in patients with coronavirus disease 2019 (COVID-19). ObjectiveTo evaluate the association between ACEIs or ARBs use and clinical outcomes in COVID-19 patients. Data SourcesSystematic search of the PubMed, Embase, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials from database inception to May 31, 2020. We also searched the preprint servers medRxiv and SSNR for additional studies. Study SelectionObservational studies and randomized controlled trials reporting the effect of ACEIs or ARBs use on clinical outcomes of adult patients with COVID-19. Data Extraction and SynthesisRisk of bias of observational studies were evaluated using the Newcastle-Ottawa Scale. Meta-analyses were performed using a random-effects models and effects expressed as Odds ratios (OR) and mean differences with their 95% confidence interval (95%CI). If available, adjusted effects were pooled. Main Outcomes and MeasuresThe primary outcome was all-cause mortality and secondary outcomes were COVID-19 severity, hospital discharge, hospitalization, intensive care unit admission, mechanical ventilation, length of hospital stay, and troponin, creatinine, procalcitonin, C-reactive protein (CRP), interleukin-6 (IL-6), and D-dimer levels. Results40 studies (21 cross-sectional, two case-control, and 17 cohorts) involving 50615 patients were included. ACEIs or ARBs use was not associated with all-cause mortality overall (OR 1.11, 95%CI 0.77-1.60, p=0.56), in subgroups by study design and using adjusted effects. ACEI or ARB use was independently associated with lower COVID-19 severity (aOR 0.56, 95%CI 0.37-0.87, p<0.01). No significant associations were found between ACEIs or ARBs use and hospital discharge, hospitalization, mechanical ventilation, length of hospital stay, and biomarkers. Conclusions and RelevanceACEIs or ARBs use was not associated with higher all-cause mortality in COVID-19. However, ACEI or ARB use was independently associated with lower COVID-19 severity. Our results support the current international guidelines to continue the use of ACEIs and ARBs in COVID-19 patients with hypertension. Key pointsO_ST_ABSQuestionC_ST_ABSWhat is the association between angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) use and clinical outcomes in coronavirus disease 2019 (COVID-19) patients? FindingsIn this systematic review and meta-analysis of 40 observational studies, the use of ACEIs or ARBs was not associated with higher all-cause mortality in COVID-19 patients. Additionally, ACEIs or ARBs use was independently associated with lower COVID-19 severity. MeaningThese results support the current international guidelines to continue the use of ACEIs and ARBs in COVID-19 patients with hypertension.