PARADISE-MI: Sacubitril/Valsartan Did Not Outperform ACE Inhibitor After MI
Sacubitril/valsartan did not significantly reduce the rate of cardiovascular death, heart failure hospitalization or outpatient heart failure requiring treatment in patients following acute myocardial infarction (AMI) compared with the ACE inhibitor ramipril, according to findings from the PARADISE-MI trial presented May 15 during ACC.21. However, the safety and tolerability of sacubitril/valsartan was comparable to that of ramipril.
The trial enrolled 5,669 patients from 495 sites in 41 countries who had experienced an AMI less than a week before enrolling in the study and had an LVEF of ≤40% and/or pulmonary congestion, plus one of eight additional risk-enhancing factors like atrial fibrillation, prior MI, diabetes, etc. None of the patients had prior heart failure. Most patients were already taking antiplatelet therapy, blood pressure lowering medications and cholesterol lowering medications.
Researchers randomized participants to receive either sacubitril/valsartan (N=2,830) or ramipril (N=2,831). Most achieved the full dose of their assigned medication and kept taking it throughout the trial, which had a median follow-up period of 23 months.
The rate of the composite primary endpoint of cardiovascular death, heart failure hospitalization or outpatient development of heart failure was 10% lower in patients taking sacubitril/valsartan compared with those taking ramipril, falling short of the prespecified threshold of a 15% reduction required to demonstrate statistically significant improvement.
However, according to the researchers, the trial found sacubitril/valsartan was well-tolerated, had a favorable safety profile and was associated with a trend toward improvement in the trial's secondary endpoints, which included cardiovascular death or heart failure hospitalization; heart failure hospitalization or outpatient treatment for heart failure; cardiovascular death, nonfatal MI or nonfatal stroke; cardiovascular death and total hospitalizations for heart failure, MI or stroke; and death from any cause.
Additionally, the rate of adverse events was equivalent in both groups, with no significant differences in the rates of angioedema, abnormal potassium levels, renal impairment or liver abnormalities. Patients taking sacubitril/valsartan showed a slightly higher rate of hypotension while patients taking ramipril were slightly more likely to report coughing. These findings offer further reassurance that sacubitril/valsartan is safe to use for patients with heart failure, the indication for which it has been approved, researchers said.
"Although we did not significantly reduce our primary endpoint, there were consistent findings that sacubitril/valsartan could represent an incremental improvement over ramipril," said Marc A. Pfeffer, MD, PhD, FACC, the study's lead author. "The results are encouraging, especially when considering recurrent heart failure events and not just the first heart failure events, but the study is not definitive. We did notice several aspects of heart failure development that were lessened with sacubitril/valsartan but to investigate these observations would require further evaluations." He adds: "This trial may not change guidelines, but it should make physicians even more comfortable using sacubitril/valsartan in their patients with heart failure."
Keywords: ACC Annual Scientific Session, ACC21, Angiotensin-Converting Enzyme Inhibitors, Heart Failure, Myocardial Infarction
< Back to Listings