Management of renin-angiotensinaldosterone system blockade in patients admitted in hospital with confirmed coronavirus disease (Covid-19) infection: The mcgill raas-covid-19 randomized controlled trial

ABSTRACT

Background: More data is needed on the cardiovascular impact of discontinuing versus continuing renin-angiotensin aldosterone system inhibitors (RAASi) among patients hospitalized with a severe acute respiratory syndrome coronavirus 2 infection (COVID-19). Methods: The McGill RAAS-COVID-19 trial was a randomized, open label trial in adult patients hospitalized with COVID-19, who were previously treated with RAASi (angiotensin converting enzyme inhibitors [ACEi]/angiotensin receptor blocker [ARB]) (NCT04508985;10/2020-03/2021). Participants were randomized 11 to discontinue or continue RAASi. The primary outcome was a global rank score calculated from baseline to day 7 (or discharge) incorporating clinical events and biomarker changes. Global rank scores were compared between groups using the Wilcoxon test statistic and the negative binomial test (using incident rate ratio [IRR]). All analyses were conducted using the intention-to-treat principle. Results: Overall, 21 participants were randomized to discontinue RAASi and 25 to continue. Patients' mean age was 71.5 years and 43.5% were female. Discontinuation of RAASi, versus continuation, resulted in a similar mean global rank score (discontinuation 6 [standard deviation [SD] 6.3] vs continuation 3.8 (SD 2.5);p= 0.60), but the negative binomial analysis identified that discontinuation increased the risk of adverse outcomes (IRR 1.7 [95% CI 1.1 to 2.6];p=0.03). Particularly, RAASi discontinuation increased brain natriuretic peptide (BNP) levels (% change from baseline +16.7% vs.-27.5%;p= 0.02) and increased the incidence of acute heart failure (33% vs. 4.2%, p=0.03). Conclusion: Discontinuation of RAASi increased BNP levels and risk of acute heart failure in participants hospitalized with COVID-19;where possible, RAASi should be continued.