No significant benefit of sacubitril/valsartan after acute MI: PARADISE-MI trial
USA: Sacubitril/valsartan does not significantly reduce the risk of heart failure (HF) or cardiovascular (CV) death for immediate post-myocardial infarction (MI) patients, compared with an ACE inhibitor, show findings from the PARADISE-MI trial. The study appears in the European Journal of Heart Failure.
According to the lead author, Marc A. Pfeffer, the safety and tolerability of sacubitril/valsartan in this acute MI population without a run-in was comparable to that of a proven, well-used ACE inhibitor. The prespecified observations of reductions in both the composite for CV total events, as well as investigator-reported events, support an incremental clinical benefit of sacubitril/valsartan, he noted.
Patients who survive an acute myocardial infarction (AMI) are at risk of developing symptomatic HF or premature death. Dr. Pfeffer and the team that sacubitril/valsartan, effective in the treatment of chronic HF, prevents the development of HF and reduces cardiovascular death following high-risk AMI compared to a proven angiotensin-converting enzyme (ACE) inhibitor.
PARADISE-MI is a multinational (41 countries), double-blind, active-controlled trial. The trial randomized patients within 0.5–7 days of presentation with index AMI to sacubitril/valsartan or ramipril. Inclusion criteria included transient pulmonary congestion and/or left ventricular ejection fraction (LVEF) ≤40% and at least one additional factor augmenting risk of HF or death (age ≥70 years, estimated glomerular filtration rate <60 mL/min/1.73 m2, diabetes, prior myocardial infarction, atrial fibrillation, LVEF <30%, Killip class ≥III, ST-elevation myocardial infarction without reperfusion).
PARADISE-MI targeted 708 primary endpoints (cardiovascular death, HF hospitalization or outpatient development of HF). Randomization of 5669 patients occurred 4.3 ± 1.8 days from the presentation with index AMI. The mean age was 64 ± 12 years, 24% were women.
The majority (76%) qualified with ST-segment elevation myocardial infarction; acute percutaneous coronary intervention was performed in 88% and thrombolysis in 6%. LVEF was 37 ± 9% and 58% were in Killip class ≥II.
Following are the key findings from the study:
- At a follow-up of 23 months, the combined endpoint of CV death, first HF hospitalization, or development of outpatient HF had occurred in 11.9% of the sacubitril/valsartan group and 13.9% of the ramipril group (HR 0.90). That translated to 7.4 events per 100 patient-years for ramipril and 6.7 events per 100 patient-years for sacubitril/valsartan.
- The components of the primary outcome all showed trends toward lower numbers of events with sacubitril/valsartan versus ramipril, but those also were not statistically significant.
- Among the 23 prespecified subgroups, only two—patients age ≥ 65 and those who received PCI—showed a trend toward greater benefit with sacubitril/valsartan than ramipril.
- For all secondary endpoints, the comparisons favored sacubitril/valsartan: CV death or HF hospitalization (HR 0.91); HF hospitalization or outpatient development of HF (HR 0.84); CV death, nonfatal MI, or nonfatal stroke (HR 0.90); CV death and total hospitalizations for HF, MI, or stroke (RR 0.84); and all-cause death (HR 0.88).
- In exploratory analysis looking at total events, however, the difference between ramipril (n = 539) and sacubitril/valsartan (n = 452) did reach statistical significance for a reduction in events (RR 0.79). Similarly, investigator-reported outcomes showed an advantage for sacubitril/valsartan over ramipril for the primary endpoint (HR 0.85), as well as for the development of outpatient HF (HR 0.69).
- Looking at adverse events, the sacubitril/valsartan group had more hypotension than did the ramipril group (28.4% vs 22.0%) but fewer reports of cough (9.0% vs 13.1%) or liver abnormalities (4.7% vs 5.9%).
- Drug discontinuation was similar in both groups, with fewer discontinuations for cough or hypotension in the sacubitril/valsartan group.
- During the trial, 242 people died in the ramipril arm and 213 died in the sacubitril/valsartan arm.
The researchers conclude that, despite the missed endpoint, sacubitril/valsartan was safe and supports an incremental clinical benefit.
Reference:
The study titled, "Prospective ARNI vs. ACE inhibitor trial to DetermIne Superiority in reducing heart failure Events after Myocardial Infarction (PARADISE-MI): design and baseline characteristics," is published in the European Journal of Heart Failure.
DOI: https://onlinelibrary.wiley.com/doi/full/10.1002/ejhf.2191
Disclaimer: This website is primarily for healthcare professionals. The content here does not replace medical advice and should not be used as medical, diagnostic, endorsement, treatment, or prescription advice. Medical science evolves rapidly, and we strive to keep our information current. If you find any discrepancies, please contact us at corrections@medicaldialogues.in. Read our Correction Policy here. Nothing here should be used as a substitute for medical advice, diagnosis, or treatment. We do not endorse any healthcare advice that contradicts a physician's guidance. Use of this site is subject to our Terms of Use, Privacy Policy, and Advertisement Policy. For more details, read our Full Disclaimer here.
NOTE: Join us in combating medical misinformation. If you encounter a questionable health, medical, or medical education claim, email us at factcheck@medicaldialogues.in for evaluation.