Prospective ARNI vs. ACE inhibitor trial to DetermIne Superiority in reducing heart failure Events after Myocardial Infarction - PARADISE-MI

Contribution To Literature:

The PARADISE-MI trial showed that sacubitril/valsartan did not reduce the primary endpoint in a contemporary enriched AMI population, compared with ramipril.

Description:

The goal of the trial was to assess the efficacy and safety of sacubitril/valsartan compared with ramipril in a contemporary acute myocardial infarction (AMI) population.

Study Design

Eligible patients were randomized in a 1:1 fashion to either sacubitril/valsartan (target dose 97/103 mg BID) (n = 2,830) or ramipril (target 5 mg BID) (n = 2,831).

  • Total number of patients: 5,661
  • Duration of follow-up: 23 months
  • Mean patient age: 64 years
  • Percentage female: 24%

Inclusion criteria:

  • Presentation with AMI
  • Left ventricular ejection fraction (LVEF) ≤40% with or without pulmonary congestion
  • Plus one of the following: age ≥70 years, atrial fibrillation, estimated glomerular filtration rate (eGFR) <60, diabetes mellitus, prior MI, LVEF <30%, Killip class ≥III, ST-segment elevation MI (STEMI) without reperfusion

Exclusion criteria:

  • Prior heart failure (HF)
  • Clinical instability
  • eGFR <30

Other salient features/characteristics:

  • White race: 76%
  • Prior MI: 16%
  • Diabetes mellitus: 43%
  • Index presentation: STEMI, 76%

Principal Findings:

The primary outcome of cardiovascular (CV) death, first HF hospitalization, or outpatient HF for sacubitril/valsartan vs. ramipril, was: 11.9% vs. 13.2% (p = 0.17).

  • CV death: 5.9% vs. 6.7% (p = 0.20)
  • HF hospitalization: 6% vs. 6.9% (p = 0.17)

Secondary outcomes for sacubitril/valsartan vs. ramipril:

  • CV death/MI/stroke: 11.1% vs. 12.3% (p = 0.18)
  • All-cause mortality: 7.5% vs. 8.5% (p = 0.16)
  • Total HF hospitalization, outpatient HF events, and CV mortality: 8.4 vs. 10.1/100 patient-years (p = 0.02)
  • Hypotension: 28.4% vs. 22.0% (p < 0.05)

Interpretation:

The results of this trial indicate that the combination sacubitril/valsartan did not reduce the primary endpoint in a contemporary enriched AMI population, compared with ramipril. Rates were numerically lower in the sacubitril/valsartan arm, and the composite endpoint that included all HF events, not just the first one, showed a benefit with sacubitril/valsartan. These are interesting findings and add to the available data with angiotensin receptor-neprilysin inhibitors (ARNIs).

References:

Presented by Dr. Marc Pfeffer at the American College of Cardiology Virtual Annual Scientific Session (ACC 2021), May 15, 2021.

Study Design Paper: Jering KS, Claggett B, Pfeffer MA, et al. Prospective ARNI vs. ACE inhibitor trial to DetermIne Superiority in reducing heart failure Events after Myocardial Infarction (PARADISEā€MI): design and baseline characteristics. Eur J Heart Fail 2021;Apr 12:[Epub ahead of print].

Clinical Topics: Acute Coronary Syndromes, Arrhythmias and Clinical EP, Cardiovascular Care Team, Heart Failure and Cardiomyopathies, ACS and Cardiac Biomarkers, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: ACC21, ACC Annual Scientific Session, Acute Coronary Syndrome, Angiotensin-Converting Enzyme Inhibitors, Atrial Fibrillation, Diabetes Mellitus, Glomerular Filtration Rate, Heart Failure, Hypotension, Myocardial Infarction, Neprilysin, Outpatients, Ramipril, Receptors, Angiotensin, Stroke, Stroke Volume, Ventricular Function, Left


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