Sacubitril-Valsartan not superior to Ramipril in acute MI setting, finds PARADISE MI trial

In this randomized, double-blind, active-controlled trial, authors randomly assigned patients with myocardial infarction complicated by a reduced EF, pulmonary congestion, or both to receive either sacubitril–valsartan (97 mg of sacubitril and 103 mg of valsartan twice daily) or ramipril (5 mg twice daily) in addition to recommended therapy.

The primary outcome was death from cardiovascular causes or incident heart failure (outpatient symptomatic heart failure or heart failure leading to hospitalization), whichever occurred first.

PARADISE-MI did not show a significant benefit of sacubitril–valsartan over the ACE inhibitor ramipril.The primary outcome of death from cardiovascular causes or incident heart failure (defined as hospitalization for heart failure or symptomatic outpatient heart failure) reached a hazard ratio of 0.90 with a P value of 0.17. The hazard ratio for the secondary outcome of heart failure events was 0.84.

Treatment with sacubitril–valsartan was associated with an incidence of hypotension that was 29% higher than that with ramipril. "The findings in PARADISE-MI do not support the use of an angiotensin receptor–neprilysin inhibitor before hospital discharge after an acute myocardial infarction, for which an ACE inhibitor or ARB is the guideline-recommended treatment", mention Stevenson et al in an accompanying editorial.

"In outpatients for whom the left ventricular ejection fraction remains low, a later switch from an ACE inhibitor or ARB to an angiotensin receptor–neprilysin inhibitor is reasonable if blood pressure and medication coverage are robust", adds Stevenson.

Source: NEJM:

1. DOI: 10.1056/NEJMe2115471

2. DOI: 10.1056/NEJMoa2104508