Effect of in-hospital treatment with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on mortality and complications in patients hospitalized for COVID-19: a large Spanish cohort study

Abstract

Background: The use of ACEI (Angiotensin-Converting Enzyme Inhibitor) and ARB (Angiotensin II Receptor Blocker) in patients with COVID-19 remains controversial, as the Renin-Angiotensin-Aldosterone System seems to have a relevant role in this disease. Our main aim was to describe the effect of ACEI/ARB treatment during COVID-19 hospitalization on mortality and complications and assess the incidence of MACE (Major Adverse Cardiovascular Events). Methods and findings: This work, part of the SEMI-COVID-19 Registry, is a retrospective, observational, multicenter study comparing patients with COVID-19 treated with ACEI/ARB during hospitalization to those not treated. The primary endpoint was incidence of the composite outcome of prognosis (IMV [Invasive Mechanical Ventilation], NIMV [Non-Invasive Mechanical Ventilation], ICU admission [Intensive Care Unit], and/or all-cause mortality). The secondary endpoint was incidence of MACE. We evaluated both outcomes in patients whose treatment with ACEI/ARB continued or was withdrawn during hospitalization. Between February and June 2020, 11,205 patients were included. The mean age was 67 years (SD=16.3) and 43.1% were female; 2,162 patients received ACEI/ARB treatment and 9,043 did not. ACEI/ARB treatment showed a protective effect on all-cause mortality (p<.0001), but was only protective in hypertensive patients in terms of IMV, ICU admission, and the composite outcome of prognosis (p<.0001 for all). No differences were found in incidence of MACE. Patients previously treated with ACEI/ARB who continued treatment during hospitalization had a lower incidence of the composite outcome of prognosis compared to those whose treatment was withdrawn (RR 0.67, 95%CI 0.63-0.76). ARB had a more beneficial effect on survival than ACEI (HR 0.77, 95%CI 0.62-0.96). The main study limitations include its retrospective, observational nature; the fact that treatment decisions were made by individual clinicians; and that treatment duration was not recorded. Conclusion: ACEI/ARB treatment during COVID-19 hospitalization was not shown to be harmful and indeed had a protective effect on mortality. The benefits were greater in hypertensive patients, those who continued treatment during hospitalization, and those taking ARB.