CV death, HF hospitalization or outpatient HF not significantly decreased by ARNI in MI patients
Angiotensin Receptor Neprilysin Inhibition (ARNI) Following Acute Myocardial Infarction: Primary Results of the PARADISE-MI Trial
Presented at ACC.21 by Marc Pfeffer, MD, PhD (Boston, MA, USA)
Introduction and methods
ACE inhibitors and ARBs (valsartan) have demonstrated benefit in post-MI patients by prolonging survival and preventing heart failure (HF). About 4-5 years ago, sacubitril/valsartan showed superiority compared to an ACE inhibitor in HF patients. This resulted in the idea to examine the efficacy and safety of sacubitril/valsartan compared to an ACE inhibitor in those with the highest risk of HF and who particularly benefit from an ACE inhibitor post-MI.
The PARADISE-MI trial enrolled MI patients within 0.5-7 days of presentation of acute MI with LVEF ≤40% and/or pulmonary congestion plus any risk enhancer. Major exclusion criteria was prior HF. There was no run-in. Patients were randomized to sacubitril/valsartan (n=2830) or ramipril (n=2831). The trial was event-driven and the primary endpoint was CV death, HF hospitalization or outpatient development of HF. Median follow-up was 23 months.
- There were 338 primary outcome events in the sacubitril/valsartan group and 373 events in the ramipril group, resulting in no statistically significant difference between the groups (HR 0.90, 95%CI: 0.78-1.04, P=0.17).
- Exploratory analyses showed a decrease in events by sacubitril/valsartan compared to ramipril when looking at total (first and recurrent) CEC adjudicated primary events and at investigator reported primary endpoint (RR 0.79, 95%CI: 0.65-0.97, P=0.02 and HR 0.85,95%CI: 0.75-0.96, P=0.01).
- Percentage reports on angioedema was similar in the sacubitril/valsartan group vs. the ramipril group, as was percentage reports on SAEs and total AEs. There were more reports on hypotension in the sacubitril/valsartan group vs. the ramipril group and vice versa less reports on cough in the sacubitril/valsartan group vs. the ramipril group. Discontinuation rate and discontinue rate due to AEs were similar between the groups.
Before concluding, Marc Pfeffer noted that this was a vigorously managed population before start of the trial, with use of primary angioplasty, statins, betablockers, etc.
In the PARADISE-MI trial, use of sacubitril/valsartan did not significantly lower CV death, HF hospitalization or outpatient HF requiring treatment compared to ramipril in MI patients with high risk of HF. Exploratory analyses, such as on total adjudicated events, suggest clinical benefit of sacubitril/valsartan. The safety and tolerability profile of sacubitril/valsartan in MI patients in a trial without a run-in period was similar to that of an ACE inhibitor.
In the end, Marc Pfeffer showed that the mortality rate in post-MI patients has gone down from 30% in the 1990s to 10% in 2021. The CV community can take credit for this, he said, by implementing the evidence. Nowadays, the bar is high to demonstrate superiority with a novel drug in clinical trials, because it has to do better than that what we already have.
The discussant Mary Norine Walsh, MD (Indianapolis, IN, USA) said that these are reassuring data on the use of sacubitril/valsartan in patients. It is being used in HF patients and she hoped for a different outcome in this trial, so that use of sacubitril/valsartan could be extended to the population with LV dysfunction post-MI. She furthermore noted that not all HF patients have access to this drug, even though it has been approved for this indication. No access to this drug in an important real world problem.
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