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Angiotensin Receptor/Neprilysin Inhibition in Patients With STEMI vs NSTEMI
abstract
This abstract is available on the publisher's site.
Access this abstract now Full Text Available for ClinicalKey SubscribersBACKGROUND
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).
Additional Info
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Angiotensin Receptor-Neprilysin Inhibition in Patients With STEMI vs NSTEMI
J Am Coll Cardiol 2024 Mar 05;83(9)904-914, DL Mann, J Nicolas, B Claggett, ZM Miao, CB Granger, P Kerkar, L Køber, EF Lewis, JJV McMurray, AP Maggioni, J Núñez, M Ntsekhe, JL Rouleau, D Sim, SD Solomon, PG Steg, P van der Meer, E Braunwald, MA Pfeffer, R MehranFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Despite significant advances in pharmacotherapy and revascularization strategies over the past decade, myocardial infarction (MI) remains associated with high morbidity and mortality. Recently, targeting the natriuretic peptide system with neprilysin inhibition has significantly improved the outcomes in patients with heart failure (HF) and reduced ejection fraction.
The PARADISE-MI trial investigated whether a similar approach would benefit high-risk patients surviving an MI complicated by left ventricular dysfunction and/or pulmonary congestion.1 Risk-enhancing factors included: age ≥70 years, estimated glomerular filtration rate <60 mL/min/1.73 m2, diabetes mellitus, prior MI, atrial fibrillation, LVEF <30%, worst Killip class III or IV, and STEMI without reperfusion therapy within the first 24 hours after presentation. Those with HF at baseline were excluded from the study. The trial showed that sacubitril/valsartan versus ramipril did not reduce the primary endpoint of cardiac death, HF hospitalization, or outpatient HF. In this prespecified analysis of the trial, Mann et al examined whether any different treatment effects between the two arms would be observed according to MI type (N = 5661; 4291 with STEMI and 1370 with NSTEMI).2 There are two main findings in this analysis. First, patients with NSTEMI had a worse prognosis than those with STEMI, even after adjusting for potential confounders in baseline risk factors (aHR, 1.19; 95% CI, 1.00–1.41). Furthermore, sacubitril/valsartan, compared with ramipril, did not significantly decrease the risk for the primary endpoint in patients with either STEMI (10% vs 12%; HR, 0.87; 95% CI, 0.73–1.04; P = .13) or NSTEMI (17% vs 17%; HR, 0.97; 95% CI, 0.75–1.25; P = .80; Pinteraction = .53) patients. Both treatment arms had relatively similar safety profiles.
The study has important implications for daily clinical practice. First, it emphasizes that differences in outcomes between patients with STEMI and NSTEMI are largely driven by differences in baseline risk factors and treatment modalities, highlighting the need to optimize management in the latter group. Second, the overall low event rates in the trial may be due to the early classification of patients as "high-risk." Reassessment of patients at an extended follow-up period after MI might help identify those at high risk of progressing toward HF and who might benefit from early initiation of sacubitril/valsartan, given its relatively good safety profile. Further studies are warranted to examine whether sacubitril/valsartan, versus other angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, would be beneficial in the long term in a select group of patients at high risk for developing HF.
References