Mortality and use of angiotensin-converting enzyme inhibitors in COVID 19 disease: a systematic review

Background: Interest exists concerning the use of angiotensin-converting enzyme inhibitors (ACEis) in patients with COVID-19 disease.

Objectives: The aim of the study was to perform a systematic review on mortality associated to the use of ACEi in patients with COVID-19 disease.

Methods: Search in Medline (PubMed), in ISI Web of Knowledge and in medRxiv database; use of other sources.

Results: A total of 33 articles were evaluated. Concerning the papers used to produce the meta-analyses, 7 studies were selected, 5 of which were used. These 5 studies involved a total number of 944 patients treated with ACEi and 5173 not treated with ACEi. Increased mortality was seen in association to the use of ACEi in the context of COVID-19 disease (ACEi users vs nonusers; odds ratio, 1.48; 95% confidence interval, 1.02-2.15; P = .04). When compared to mortality in patients treated with angiotensin receptor blockers, mortality of patients treated with ACEi was not significantly different (odds ratio, 0.96; 95% confidence interval, 0.76-1.21; P = .74). Concerning the remaining reports, different types of data adjustments were used by several authors, after which increased mortality was not seen in association to the use of ACEi in this context.

Conclusions: ACEi use could act as a marker of increased mortality risk in some but not all COVID-19 disease settings. The data now presented do not prove a causal relation but argue in favor of carrying out clinical trials studying ACEi in COVID-19 patients, to establish the safety of ACEi use in this context.