PARADISE-MI Study Evaluated Sacubitril/Valsartan in Acute Myocardial Infarction
The PARADISE-MI (Prospective ARNI vs ACE Inhibitor Trial to DetermIne Superiority in reducing heart failure Events after Myocardial Infarction) trial is the definitive study that evaluated the use of sacubitril/valsartan in patients with acute myocardial infarction. 1, 2
Study Design and Population
PARADISE-MI was a multinational, double-blind, active-controlled trial that:
- Randomized 5,661 patients within 0.5-7 days after acute myocardial infarction
- Compared sacubitril/valsartan (97/103 mg twice daily) to ramipril (5 mg twice daily)
- Enrolled patients with:
- Left ventricular ejection fraction (LVEF) ≤40% and/or
- Transient pulmonary congestion
- At least one additional risk factor (age ≥70 years, eGFR <60 mL/min/1.73m², diabetes, prior MI, atrial fibrillation, LVEF <30%, Killip class ≥III, or STEMI without reperfusion)
- Median follow-up of 22 months
Key Findings
The PARADISE-MI trial found that:
- The primary outcome of cardiovascular death or incident heart failure occurred in 11.9% of patients in the sacubitril/valsartan group versus 13.2% in the ramipril group (hazard ratio 0.90; 95% CI 0.78-1.04; p=0.17) 2
- This did not meet the threshold for statistical significance
- A prespecified secondary analysis showed that sacubitril/valsartan did reduce major coronary events compared to ramipril (hazard ratio 0.86; 95% CI 0.74-0.99; p=0.04) 3
Clinical Context
The PARADISE-MI trial was designed to determine if the benefits of sacubitril/valsartan observed in chronic heart failure could extend to the post-MI setting:
- Prior to this trial, ACE inhibitors were the standard of care for patients with MI and reduced ejection fraction 4
- The trial was specifically designed to test whether sacubitril/valsartan could prevent the development of heart failure and reduce cardiovascular death following high-risk MI 1
- Most patients (76%) had ST-segment elevation MI, with 88% undergoing acute percutaneous coronary intervention and 6% receiving thrombolysis 1
Safety Considerations
- Symptomatic hypotension was more common with sacubitril/valsartan (28.3%) compared to ramipril (21.9%) 5
- Overall discontinuation rates due to adverse events were similar: 12.6% in the sacubitril/valsartan group versus 13.4% in the ramipril group 2
Current Guideline Recommendations
Despite the neutral primary outcome of PARADISE-MI, guidelines acknowledge the potential role of sacubitril/valsartan in specific post-MI populations:
- The American College of Cardiology/American Heart Association guidelines note that sacubitril/valsartan can fulfill criteria for ACEI/ARB therapy in patients with MI and left ventricular systolic dysfunction 4
- However, ACE inhibitors remain the first-line recommendation for post-MI patients with reduced ejection fraction 4
Implications for Practice
Based on the PARADISE-MI findings, ACE inhibitors should remain the preferred initial therapy for most patients after acute MI with reduced ejection fraction, with sacubitril/valsartan considered in specific situations where additional benefits might outweigh the increased risk of hypotension.