Cardiovascular events after acute myocardial infarction complicated by low ejection fraction and/or congestion: a landmark analysis of the PARADISE-MI trial

AIMS: Despite improvements in post-acute myocardial infarction (AMI) care, the risk of subsequent cardiovascular (CV) events remains substantial, particularly heart failure (HF) in patients with left ventricular systolic dysfunction (LVSD) and/or pulmonary congestion. METHODS: The PARADISE-MI trial randomized 5661 patients with AMI complicated by LVSD and/or pulmonary congestion to sacubitril/valsartan (97/103 mg bid) or ramipril (5 mg bid) at a mean of 4 days post-AMI. This post hoc analysis described the timing and distribution of CV events, and compared treatment effects in early (≤ 3 months) and late (> 3 months) post-AMI periods. RESULTS: Post-AMI, CV events peaked early; HF was the most frequent (16.2/100 patient-years (py)), followed by CV death (11.6/100 py) and recurrent MI (10.9/100 py). Later, HF remained predominant (3.2/100 py vs. 2.6/100 py for MI, p=0.008; CV death 2.1/100 py). Early post-AMI, patients with HF or recurrent MI shared similar profiles. Later, HF patients were predominantly older and female, with greater pulmonary congestion and lower eGFR; recurrent MI patients had more frequent history of coronary revascularization. Only sacubitril/valsartan showed a favorable influence late post-AMI (HR 0.76, 95% CI 0.60-1.00, p=0.05) and expanded CV composite outcome (CV death, HF events, recurrent MI, hospitalization for angina, or post-randomization coronary revascularization) benefit over the trial (HR=0.87, 95% CI 0.77-0.97, p=0.012). CONCLUSIONS: Post-AMI, HF predominates both early and late among CV events. Compared with ramipril, sacubitril/valsartan was associated with a possible late reduction in recurrent MI and a modest decrease in an expanded CV composite outcome that merits further investigation.