ANGIOTENSIN RECEPTOR BLOCKERS AND ANGIOTENSIN CONVERTING ENZYME INHIBITORS IN COVID-19 –META-ANALYSIS/META-REGRESSION ADJUSTED FOR CONFOUNDING FACTORS

Background Angiotensin receptor blockers (ARBs) and/or angiotensin converting enzyme (ACE) inhibitors could alter mortality of COVID-19, but existing meta-analyses which combined crude and adjusted results may be confounded by comorbidities being more common in ARBs/ACE inhibitors users. Methods We searched PubMed/MEDLINE/Embase for cohort studies and meta-analysis reporting mortality by pre-existing ARB/ACE inhibitor treatment in hospitalized COVID-19 patients. Random effects meta-regression was used to compute pooled odds ratios for mortality adjusted for imbalance in age, sex and prevalence of cardiovascular disease, hypertension, diabetes mellitus and chronic kidney disease between users and non-users of ARBs/ACE inhibitors at the study-level during data synthesis. Results In 30 included studies of 17,281 patients, 22%, 68%, 25%, and 11% had cardiovascular disease, hypertension, diabetes mellitus and chronic kidney disease. ARBs/ACE inhibitors use was associated with significantly lower mortality after controlling for potential confounding factors (OR 0.77 (95% CI: 0.62, 0.96)). In contrast, meta-analysis of ARBs/ACE inhibitors use was not significantly associated with mortality when all studies were combined with no confounder adjustment performed (0.87 (95% CI: 0.71, 1.08)). Conclusions ARBs/ACE inhibitors use was associated with decreased mortality in cohorts of COVID-19 patients after adjusting for age, sex, cardiovascular disease, hypertension, diabetes and chronic kidney disease. Unadjusted meta-analyses may not be appropriate for determining whether ARBs/ACE inhibitors are associated with mortality of COVID-19 because of indication bias.