Early Pre-Reperfusion Metoprolol in Patients With Acute Myocardial Infarction

Amy Leigh Miller, Joseph Loscalzo


AccessMedicine from McGraw-Hill 

ST-segment myocardial infarction (STEMI) causes significant morbidity and mortality, with infarct size being the primary predictor of clinical outcome. Given imaging evidence that early IV metoprolol infusion is associated with a reduction in infarct size, Pizarro and colleagues (2014) examined the effects of early metoprolol infusion on long-term clinical outcomes in STEMI patients in a multicenter, randomized, controlled trial. A total of 270 patients presenting with STEMI were randomized to pre-reperfusion IV metoprolol administration (up to 3 boluses of 5 mg each) or standard care (control). Exclusion criteria included Killip class >II, symptom onset to reperfusion time >6 h, persistent hypotension, bradycardia, atrioventricular block, prior infarct, and/or active treatment with beta blockers. Local treating physicians were blind to treatment allocation. All patients received long-term oral beta blockers starting within 24 h of admission unless there was a contraindication to such therapy. Infarct size was assessed with MRI 1 week post-infarction, with repeat imaging 6 months post-infarction if the initial study demonstrated delayed gadolinium enhancement. The primary outcome was a composite endpoint of death, heart failure readmission, reinfarction, and ventricular arrhythmia. Patients were followed for a median of 2 years, with a minimum follow-up of 1 year.

A previous analysis from this population demonstrated a 20% reduction in infarct size in patients receiving IV metoprolol, relative to controls, at 1 week post-infarction. In this analysis, IV metoprolol administration was associated with better left ventricular ejection fraction (48.7 ± 9.9% vs 45.0 ± 11.7%) and lower left ventricular end-systolic volume (98.1 ± 36.0 mL vs 112.0 ± 45.0 mL) at 6 months post-infarction. Only 11% of patients in the IV metoprolol group had an ejection fraction low enough (≤35%) for consideration of a primary-prevention implantable cardioverter defibrillator (ICD) at 6 months, compared with 27% of control patients, and significantly fewer patients in the IV metoprolol group met a class I indication for an ICD [7% vs 20%; adjusted odds ratio, 0.32; 95% confidence interval (CI), 0.13—0.81]. The composite endpoint occurred in 10.8% of patients in the IV metoprolol group compared with 18.3% of control subjects [adjusted hazard ratio (HR), 0.55; 95% CI, 0.26–1.04; p = .065], driven primarily by fewer heart failure admissions in the metoprolol group (2.2% vs 6.9%; adjusted HR, 0.32; 95% CI, 0.015–0.95; p = .046).

While not statistically significant, the strong trend in the prespecified composite outcome, along with the significant difference in the secondary analysis (heart failure readmission), stands in contrast to the findings of the COMMIT trial, which found no benefit of early metoprolol administration in patients who underwent thrombolysis for STEMI. This may reflect more prudent exclusion criteria employed in METOCARD-CNIC and/or longer follow-up that better captured long-term benefits of early metoprolol. The results of METOCARD-CNIC suggest that, in a subset of STEMI patients, early IV metoprolol may have significant clinical benefit. Larger-scale studies will, however, be necessary to definitively assess the role of IV metoprolol in this population