Sacubitril/valsartan compared to ramipril in high‐risk post myocardial infarction patients stratified according use of mineralocorticoid receptor antagonists: Insight from PARADISE MI trial

Abstract Background It is unknown whether safety and clinical endpoints by use of sacubitril/valsartan (ARNI) is affected by Mineralocorticoid receptor antagonists (MRA) in high‐risk myocardial infarction (MI) patients. Purpose To examine whether MRA modifies safety and clinical endpoints by use of sacubitril/valsartan in patients with a MI and left ventricular systolic dysfunction (LVSD) and/or pulmonary congestion. Methods Patients (N=5661) included in the PARADISE MI Trial (Prospective ARNI vs. ACE inhibitor trial to DetermIne Superiority in reducing heart failure (HF) Events after MI) were stratified according to MRA. Primary outcomes in this substudy were worsening HF or cardiovascular death. Safety was defined as symptomatic hypotension, hyperkalemia > 5.5 mmol/L or permanent drug discontinuation. Results 2338 patients (41%) were treated with MRA. Safety of ARNI compared to ramipril was not altered significantly by +/‐MRA, and both groups had similar increase in symptomatic hypotension with ARNI. In patients taking MRA, the risk of hyperkalemia or permanent drug discontinuation was not significantly altered by ARNI (P> 0.05 for all comparisons). The effect of ARNI compared with ramipril was similar in those who were and were not taking MRA: hazard ratio MRA : (95% confidence interval [CI]): 0.96 (0.77, 1.19) versus (HR MRA‐ 0.87 (95% CI: 0.71, 1.05), respectively, for the primary endpoint (p value for interaction = 0.51) (CEC adjudicated); similar findings were observed if investigator reported endpoints were evaluated (P = 0.61 for interaction). Conclusions Use of a MRA did not modify safety or clinical endpoints related to initiation of ARNI compared to ramipril in the post MI setting in patients with LVSD and/or congestion. This article is protected by copyright. All rights reserved.