Firibastat Versus Ramipril After Acute Mechanical Reperfusion of Anterior Myocardial Infarction: A Phase 2 Study.

ABSTRACT

BACKGROUND: Preclinical data suggest that central renin-angiotensin system blockade by the brain aminopeptidase-A inhibitor firibastat can improve left ventricular ejection fraction (LVEF) after myocardial infarction (MI). OBJECTIVES: This study aimed to compare the effect of firibastat versus ramipril on post-MI LVEF. METHODS: In this phase 2, randomized, double-blind trial, patients selected within 24 h of first acute anterior MI treated by primary percutaneous coronary intervention were randomly assigned (111) to firibastat 100 mg, firibastat 500 mg or ramipril 5 mg, each twice daily for 12 weeks. The primary endpoint was change in LVEF on cardiac magnetic resonance imaging (cMRI) from baseline to day 84 in the modified intent-to-treat (mITT) population (at least one dose received and one follow-up cMRI available) for each treatment group. RESULTS: From June 4, 2019 to April 12, 2021, 294 patients were randomized and 229 were evaluable for the mITT analysis. After 12 weeks, mean ± standard deviation (SD) percent change in LVEF was 5.6 ± 1.2 with firibastat 100 mg, 5.3 ± 1.1 with firibastat 500 mg and 5.7 ± 1.1 with ramipril. The absolute ± SE adjusted difference in LVEF change from baseline between firibastat 500 mg and ramipril was - 0.36 ± 1.32% (p = 0.79). Occurrence of treatment-related adverse events was similar in the three groups. CONCLUSIONS: Firibastat was not superior to ramipril for prevention of left ventricular dysfunction after first acute anterior MI, and their safety profiles were similar. REGISTRATION ClinicalTrials.gov identifier NCT03715998.