The literature examining the utility of beta blockers in the setting of acute coronary syndrome (ACS) to limit infarct size has produced conflicting results within and across treatment eras. Animal data suggest that beta blockers can reduce infarct size in patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous intervention (PCI), but only if administered prior to reperfusion. However, in the absence of randomized clinical trials supporting this benefit, current consensus guidelines advocate only for initiation of beta blockade within 24 h of presentation. The METOCARD-CNIC trial (Ibanez et al., 2013) was a multicenter, prospective, randomized, blind-endpoint study comparing early IV metoprolol (prior to reperfusion) to no metoprolol prior to reperfusion. Patients were eligible for enrollment if they presented with an anterior STEMI, if their symptom duration was >30 min, and if reperfusion could be performed within 6 h of symptom onset. Exclusion criteria included Killip class III or IV, PR interval >240 ms, type II or III atrioventricular block, systolic blood pressure <120 mmHg, heart rate <60 bpm persistently, history of prior MI, or currently active beta blocker therapy. Following informed consent, patients were randomized (in strata according to time of onset, diabetes status, sex, and age) to the treatment arm (up to three 5-mg boluses of metoprolol tartrate at 2-min intervals) or the control arm (no beta blocker prior to reperfusion). All other treatment was identical for the two groups, including a recommendation for thrombus aspiration and glycoprotein IIb/IIIa use as well as initiation of oral metoprolol tartrate after revascularization, if not contraindicated. Patients without enzymatic evidence of infarction were excluded from analysis. MRI was performed 5–7 days after infarction in all other patients. Infarct size was quantified by delayed gadolinium enhancement at a core laboratory by blind observers.
A total of 270 patients were randomized (131 to the control group, 139 to the IV metoprolol group); 2 patients from each group withdrew consent, 24 patients were excluded prior to MRI, and 22 patients could not undergo planned MRI. A total of 220 patients (106 receiving metoprolol, 114 controls) were included in the analysis. Relative to controls, infarct size was significantly lower (25.6 ± 15.3 vs 32.0 ± 22.2 g; p = .012) in patients treated with IV metoprolol. This difference was greatest in patients with TIMI grade 0–1 flow prior to PCI; in this cohort, infarct size was 26.7 ± 15.0 g in patients treated with IV metoprolol, and 34.4 ± 20.0 g in controls (p = .0024). There was no evidence of a protective effect in patients with pre-PCI TIMI grade 2–3 flow (p = .6). A similar pattern was observed in the peak creatine kinase (CK) level and area under the curve of CK release, as well as in left ventricular ejection fraction as assessed by MRI. There was no difference in adverse cardiac events between groups in the first 24 h. There was, however, a trend toward a higher rate of progression to Killip class III/IV in patients treated with metoprolol (7.9% vs 6.9%; no statistics provided).
The design of this trial incorporated lessons learned from the Clopidogrel and Metoprolol in Myocardial Infarction Trial (COMMIT), excluding patients in whom IV metoprolol was associated with an increased risk of cardiogenic shock. While the statistical significance of the higher rate of progression to Killip class III/IV in the IV metoprolol arm was not examined in the manuscript, the absolute difference in the rate of progression is relatively small. The study suggests that in Killip class I/II patients presenting soon after onset of symptoms, IV metoprolol may reduce infarct size. The long-term clinical implications of this effect have yet to be characterized.
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