Angiotensin Receptor-Neprilysin Inhibition in Patients With STEMI vs NSTEMI

J Am Coll Cardiol. 2024 Mar 5;83(9):904-914. doi: 10.1016/j.jacc.2024.01.002.


Background: Patients who sustain an acute myocardial infarction (AMI), including ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI), remain at high risk for heart failure (HF), coronary events, and death. Angiotensin-converting enzyme inhibitors have been shown to significantly decrease the risk for cardiovascular events in both STEMI and NSTEMI patients.

Objectives: The objectives were to determine whether angiotensin-receptor blockade and neprilysin inhibition with sacubitril/valsartan, compared with ramipril, has impact on reducing cardiovascular events according to the type of AMI.

Methods: The PARADISE-MI (Prospective ARNI versus ACE inhibitor trial to DetermIne Superiority in reducing heart failure Events after Myocardial Infarction) trial enrolled patients with AMI complicated by left ventricular dysfunction and/or pulmonary congestion and at least 1 risk-enhancing factor. Patients were randomized to either sacubitril/valsartan or ramipril. The primary endpoint was death from cardiovascular causes or incident HF. In this prespecified analysis, we stratified patients according to AMI type.

Results: Of 5,661 enrolled patients, 4,291 (75.8%) had STEMI. These patients were younger and had fewer comorbidities and cardiovascular risk factors than NSTEMI patients. After adjustment for potential confounders, the risk for the primary outcome was marginally higher in NSTEMI vs STEMI patients (adjusted HR: 1.19; 95% CI: 1.00-1.41), with borderline statistical significance (P = 0.05). The primary composite outcome occurred at similar rates in patients randomized to sacubitril/valsartan vs ramipril in STEMI (10% vs 12%; HR: 0.87; 95% CI: 0.73-1.04; P = 0.13) and NSTEMI patients (17% vs 17%; HR: 0.97; 95% CI: 0.75-1.25; P = 0.80; P interaction = 0.53).

Conclusions: Compared with ramipril, sacubitril/valsartan did not significantly decrease the risk for cardiovascular death and HF in patients with AMI complicated by left ventricular dysfunction, irrespective of the type of AMI. (Prospective ARNI vs ACE Inhibitor Trial to Determine Superiority in Reducing Heart Failure Events After MI; NCT02924727).

Keywords: acute myocardial infarction; ramipril; sacubitril/valsartan.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aminobutyrates / pharmacology
  • Angiotensin Receptor Antagonists / pharmacology
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Angiotensins
  • Biphenyl Compounds
  • Heart Failure*
  • Humans
  • Myocardial Infarction* / drug therapy
  • Neprilysin
  • Non-ST Elevated Myocardial Infarction* / drug therapy
  • Prospective Studies
  • Ramipril
  • Receptors, Angiotensin
  • ST Elevation Myocardial Infarction* / drug therapy
  • Tetrazoles / pharmacology
  • Treatment Outcome
  • Valsartan
  • Ventricular Dysfunction, Left* / chemically induced


  • sacubitril
  • Neprilysin
  • Ramipril
  • Angiotensins
  • Receptors, Angiotensin
  • Tetrazoles
  • Valsartan
  • Aminobutyrates
  • Biphenyl Compounds
  • Angiotensin-Converting Enzyme Inhibitors
  • Angiotensin Receptor Antagonists

Associated data