Treatment with ACE inhibitors or ARBs and risk of severe/lethal COVID-19: a meta-analysis

Flacco, Maria Elena; Acuti Martellucci, Cecilia; Bravi, Francesca; Parruti, Giustino; Cappadona, Rosaria; Mascitelli, Alfonso; Manfredini, Roberto; Mantovani, Lorenzo G; Manzoli, Lamberto

OBJECTIVE: It has been hypothesised that the use of ACE inhibitors and angiotensin receptor blockers (ARBs) might either increase or reduce the risk of severe or lethal COVID-19. The findings from the available observational studies varied, and summary estimates are urgently needed to elucidate whether these drugs should be suspended during the pandemic, or patients and physicians should be definitely reassured. This meta-analysis of adjusted observational data aimed to summarise the existing evidence on the association between these medications and severe/lethal COVID-19. METHODS: We searched MedLine, Scopus and preprint repositories up to 8 June 2020 to retrieve cohort or case–control studies comparing the risk of severe/fatal COVID-19 (either mechanical ventilation, intensive care unit admission or death), among hypertensive subjects treated with: (1) ACE inhibitors, (2) ARBs and (3) both, versus untreated subjects. Data were combined using a random-effect generic inverse variance approach. RESULTS: Ten studies, enrolling 9890 hypertensive subjects were included in the analyses. Compared with untreated subjects, those using either ACE inhibitors or ARBs showed a similar risk of severe or lethal COVID-19 (summary OR: 0.90; 95% CI 0.65 to 1.26 for ACE inhibitors; 0.92; 95% CI 0.75 to 1.12 for ARBs). The results did not change when both drugs were considered together, when death was the outcome and excluding the studies with significant, divergent results. CONCLUSION: The present meta-analysis strongly supports the recommendation of several scientific societies to continue ARBs or ACE inhibitors for all patients, unless otherwise advised by their physicians who should thus be reassured.