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

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 (1:1:1) 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.