ARNI may reduce total heart failure events in patients with acute MI
Impact of Sacubitril/Valsartan Versus Ramipril on Total Heart Failure Events in the PARADISE-MI trial
Introduction and methods
In the PARADISE MI trial, sacubitril/valsartan did not reduce the primary composite outcome of time to CV death of time to first heart failure event (hospitalization or outpatient) compared to ramipril in patients with acute myocardial infarction .
In this analysis, additional prespecified end points were explored, which could provide information on the effects of ARNI in high-risk patients after MI. More specifically, this analysis focused on total (first and recurrent) clinical end point committee (CEC)-adjudicated and investigator-reported events.
PARADISE-MI was a double-blind, active-controlled, randomized, clinical trial in which sacubitril/valsartan was compared with ramipril in 5661 patients with acute MI and either left ventricular ejection fraction ≤40% or transient pulmonary congestion. Patients with previous heart failure of clinical instability were excluded.
Investigator-reported time-to-first event and occurrence of recurrent events (hospitalizations for heart failure, outpatient heart failure, or CV death).
- There were 443 patients (15.7%) with a first investigator-reported CV death, hospitalization for HF, or outpatient HF in the sacubitril/valsartan group and 516 patients (18.2%) in the ramipril group (HR 0.85, 95%CI: 0.75-0.96, P=0.01).
- In the sacubitril/valsartan group, there were a total of 452 CEC-adjudicated primary events, whereas there were 539 total events in the ramipril group (RR 0.79, 95%CI: 0.65-0.97, P=0.020).
- There were 672 investigator-reported total events in the sacubitril/valsartan group, whereas there were 802 total event in the ramipril group (RR 0.79, 95%CI: 0.67-0.93, P=0.004).
- Use of open label sacubitril/valsartan in patients developing symptomatic HF during the trial was low (<10%).
This exploratory analysis of PARADISE-MI suggest that recurrent HF events using both CEC adjudications and investigator reports are reduced by sacubitril/valsartan. The authors conclude that these findings provide supportive information for the already indicated replacement of an ACEi with sacubitril/valsartan once the development to symptomatic HF has occurred.