Prospective ARNI versus ACE inhibitor trial to DetermIne Superiority in reducing heart failure Events after Myocardial Infarction (PARADISE-MI): Design and Baseline Characteristics.

Jering, Karola S; Claggett, Brian; Pfeffer, Marc A; Granger, Christopher; Køber, Lars; Lewis, Eldrin F; Maggioni, Aldo P; Mann, Douglas; McMurray, John J V; Rouleau, Jean-Lucien; Solomon, Scott D; Steg, Philippe G; van der Meer, Peter; Wernsing, Margaret; Carter, Katherine; Guo, Weinong; Zhou, Yinong; Lefkowitz, Martin; Gong, Jianjian; Wang, Yi; Merkely, Bela; Macin, Stella M; Shah, Urmil; Nicolau, Jose C; Braunwald, Eugene

AIMS Patients surviving an acute myocardial infarction (AMI) are at risk of developing symptomatic heart failure (HF) or premature death. We hypothesized that sacubitril/valsartan, effective in the treatment of chronic HF, prevents development of HF and reduces cardiovascular death following high-risk AMI compared to a proven ACE inhibitor. This paper describes the study design and baseline characteristics of patients enrolled in the Prospective ARNI versus ACE inhibitor trial to DetermIne Superiority in reducing heart failure Events after Myocardial Infarction (PARADISE-MI) trial. METHODS AND RESULTS PARADISE-MI, a multinational (41 countries), double-blind, active-controlled trial, randomized patients within 0.5-7 days of presentation with index AMI to sacubitril/valsartan or ramipril. Transient pulmonary congestion and/or LVEF ≤ 40% and at least one additional factor augmenting risk of HF or death (age ≥70 years, eGFR <60ml/min/1.73m2 , diabetes, prior MI, atrial fibrillation, LVEF <30%, Killip class ≥III, STEMI without reperfusion) were required for inclusion. PARADISE-MI was event-driven targeting 708 primary endpoints [cardiovascular (CV) death, HF hospitalization or outpatient development of HF]. Randomization of 5669 patients occurred 4.3 ± 1.8 days from presentation with index AMI. The mean age was 64 ± 12 years, 24% were women. The majority (76%) qualified with ST-segment elevation MI; acute percutaneous coronary intervention was performed in 88% and thrombolysis in 6%. LVEF was 37 ± 9% and 58% were Killip class ≥2. CONCLUSIONS Baseline therapies in PARADISE-MI reflect advances in contemporary evidence-based care. With enrollment complete PARADISE-MI is poised to determine whether sacubitril/valsartan is more effective than a proven ACE inhibitor in preventing development of HF and CV death following AMI.