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Angiotensin Receptor-Neprilysin Inhibition in Patients With STEMI vs NSTEMI
Douglas L Mann1, Johny Nicolas2, Brian Claggett3
1Washington University School of Medicine, St Louis, Missouri, USA.
Insights
Sacubitril/valsartan did not significantly reduce cardiovascular death or heart failure after acute myocardial infarction (AMI), regardless of whether it was ST-elevation (STEMI) or non-ST-elevation (NSTEMI). Ramipril showed similar efficacy in both STEMI and NSTEMI patient groups.
Area of Science:
- Cardiology
- Clinical Trials
- Pharmacology
Background:
- Patients with acute myocardial infarction (AMI), including STEMI and NSTEMI, face high risks of heart failure (HF), recurrent coronary events, and mortality.
- Angiotensin-converting enzyme (ACE) inhibitors are established treatments that reduce cardiovascular event risk in AMI patients.
Purpose of the Study:
- To compare the efficacy of sacubitril/valsartan (angiotensin-receptor blockade and neprilysin inhibition) versus ramipril (ACE inhibitor) in reducing cardiovascular events in patients following AMI.
- To specifically analyze the impact of AMI type (STEMI vs. NSTEMI) on the treatment outcomes.
Main Methods:
- The PARADISE-MI trial randomized patients with AMI, left ventricular dysfunction, and/or pulmonary congestion to receive either sacubitril/valsartan or ramipril.
- The primary endpoint was cardiovascular death or incident heart failure. This analysis prespecified stratification based on AMI type (STEMI vs. NSTEMI).
Main Results:
- Of 5,661 patients, 75.8% had STEMI. NSTEMI patients were younger with fewer risk factors than STEMI patients.
- The primary outcome risk was marginally higher in NSTEMI versus STEMI patients (adjusted HR: 1.19; P=0.05).
- Sacubitril/valsartan and ramipril demonstrated similar rates for the primary composite outcome in both STEMI (HR: 0.87; P=0.13) and NSTEMI (HR: 0.97; P=0.80) groups, with no significant interaction by AMI type (P=0.53).
Conclusions:
- Sacubitril/valsartan did not significantly reduce the risk of cardiovascular death or heart failure compared to ramipril in patients with AMI and left ventricular dysfunction.
- The findings were consistent across both STEMI and NSTEMI patient subgroups, indicating no differential benefit based on AMI type.
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).
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