Clinical Efficacy and Safety of Early Intravenous Administration of Beta-Blockers in Patients Suffering from Acute ST-Segment Elevation Myocardial Infarction Without Heart Failure Undergoing Primary Percutaneous Coronary Intervention: A Study-Level Meta-Analysis of Randomized Clinical Trials
Authors: Sun Bing , Wang Chi Yao , Chen Rui Rui 
Published: April 2023

Abstract
Background
Several clinical studies have produced diverse results regarding the efficacy and safety of early intravenous beta-blockers in patients with acute ST-segment elevation myocardial infarction (STEMI). A study-level meta-analysis of randomized clinical trials (RCTs) comparing early intravenous beta-blockers versus placebo or routine care in STEMI patients undergoing primary percutaneous coronary intervention (PCI) was performed.

Methods
A database search was conducted using PubMed, EMBASE, the Cochrane Library, and Clinicaltrials.gov for randomized clinical trials (RCTs) that compared intravenous beta-blockers versus placebo or routine care in STEMI patients who underwent primary PCI. The efficacy outcomes were infarct size (IS, % of LV) and the myocardial salvage index (MSI) based on magnetic resonance imaging, electrocardiographic findings, heart rate, ST-segment reduction percent (STR%), and complete STR. Safety outcomes included arrhythmias in the first 24 h (ventricular tachycardia and fibrillation [VT/VF], atrial fibrillation [AF], bradycardia, and advanced atrioventricular [AV] block), cardiogenic shock and hypotension during hospitalization, left ventricular ejection fraction (LVEF), and major adverse cardiovascular events (cardiac death, stroke, reinfarction, and heart failure readmission) at follow-up.

Results
Seven RCTs with 1428 patients were included in this study, with 709 patients in the intravenous beta-blockers and 719 in the control group. Intravenous beta-blockers improved MSI compared to the control group (weighted mean difference [WMD] 8.46, 95% confidence interval [CI] 3.12–13.80, P = 0.002, I2 = 0%), but no differences were observed in IS (% of LV) between groups. Compared to the control group, the intravenous beta-blockers group had a lower risk of VT/VF (relative risk [RR] 0.65, 95% CI 0.45–0.94, P = 0.02, I2 = 35%) without an increase of AF, bradycardia, and AV-block and significantly decreased HR, hypotension. LVEF at 1 week ± 7 days (WMD 2.06, 95% CI 0.25–3.88, P = 0.03, I2 = 12%) and 6 months ± 7 days (WMD 3.24, 95% CI 1.54–4.95, P = 0.0002, I2 = 0%) was improved in the intravenous beta-blockers group compared to the control group. Subgroup analysis showed that intravenous beta-blockers before PCI decreased the risk of VT/VF and improved LVEF compared to the control group. Furthermore, sensitivity analysis showed that patients with a left anterior descending (LAD) artery lesion had a smaller IS (% of LV) in the intravenous beta-blockers group compared to the control group.

Conclusion
Intravenous beta-blockers improved the MSI, decreased the risk of VT/VF in the first 24 h, and were associated with increased LVEF at 1 week and 6 months following PCI. In particular, intravenous beta-blockers started before PCI is beneficial for patients with LAD lesions.