Evaluating the effects of sacubitril/valsartan with ST-elevated myocardial infarction: a systematic review and meta-analysis

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.