Key result
Sacubitril/valsartan cuts MACE ~34% vs ACEIs in STEMI patients, alongside fewer heart failure hospitalizations.
Why the study?
Although ACEIs are standard therapy after STEMI, emerging evidence suggests sacubitril/valsartan may confer superior cardioprotection, requiring systematic evaluation of its efficacy and safety versus ACEIs.
Does sacubitril/valsartan reduce major adverse cardiovascular events compared to ACEIs in patients with STEMI?
Meta-Analysis (n=4,915)
Does sacubitril/valsartan reduce major adverse cardiovascular events compared to ACEIs in patients with STEMI?
Effect estimate: RR 0.66 (95% CI 0.50, 0.86)
p-value: p=0.002
In patients with STEMI, sacubitril/valsartan significantly reduces MACE and heart failure hospitalizations and improves LVEF compared to ACEIs, without increasing adverse safety events.
Supports preferential sacubitril/valsartan over ACE inhibitors in practice; reinforces Level 1 randomized evidence.
Background: ST-segment elevation myocardial infarction (STEMI) continues to be a leading cause of cardiovascular (CV) morbidity and mortality worldwide, posing an ongoing clinical and public health burden. Although angiotensin-converting enzyme inhibitors (ACEIs) remain integral to guideline-recommended therapy following STEMI, recent evidence indicates that sacubitril/valsartan may offer superior cardioprotective benefits. This meta-analysis aims to systematically evaluate and compare the efficacy and safety of sacubitril/valsartan versus ACEIs in the management of patients with STEMI. Methods: PubMed and Cochrane databases were systematically searched from inception to July 2024 to identify randomized controlled trials (RCTs) comparing sacubitril/valsartan and ACEIs in patients with STEMI. Data were synthesized using a random-effects model to calculate risk ratios (RRs) and weighted mean differences (WMDs), each with 95% confidence intervals (CIs). A P -value < 0.05 was considered statistically significant. Results: A total of five RCTs comprising 4915 participants were included in the final analysis. Sacubitril/valsartan therapy was associated with a significant reduction in major adverse cardiovascular events (MACE) [RR: 0.66 (0.50, 0.86); P = 0.002] and hospitalizations for heart failure (HHF) [RR: 0.67 (0.49, 0.92); P = 0.01]. Treatment with sacubitril/valsartan also significantly improved left ventricular ejection fraction (LVEF) [WMD: 2.60 (1.53, 3.68); P < 0.00001] and reduced NT-proB-type natriuretic peptide (NT-proBNP) levels (WMD: −268.89 [−422.35, −115.42]; P = 0.0006). No significant differences were observed in the risk of recurrent myocardial infarction [RR: 1.02 (0.39, 2.71); P = 0.96), CV death [RR: 0.78 (0.61, 1.01); P = 0.06], or all-cause mortality [RR: 0.85 (0.68, 1.06); P = 0.15]. Safety analyses revealed no significant differences in the risk of cough [RR: 0.63 (0.15, 2.72); P = 0.54], hypotension [RR: 1.68 (0.97, 2.91); P = 0.06], worsening renal function [RR: 0.51 (0.22, 1.21); P = 0.13], or hyperkalemia [RR: 0.59 (0.17, 2.01); P = 0.40]. Conclusion: Sacubitril/valsartan therapy significantly reduces MACE and HHF and improves LVEF in patients with STEMI, without increasing the risk of adverse safety outcomes. Future well-powered randomized trials are needed to confirm these results and support clinical guideline recommendations.
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Kumar et al. (2026) conducted a meta-analysis in ST-segment elevation myocardial infarction (STEMI) (n=4,915). sacubitril/valsartan vs. ACEIs was evaluated on major adverse cardiovascular events (MACE) (RR 0.66, 95% CI 0.50, 0.86, p=0.002). Sacubitril/valsartan significantly reduced major adverse cardiovascular events (RR 0.66; 95% CI 0.50-0.86; P=0.002) and heart failure hospitalizations compared to ACEIs in patients with STEMI.
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