WASHINGTON – Early administration of intravenous metoprolol prior to primary percutaneous coronary intervention in patients with Killip class I or II anterior ST-elevation myocardial infarction reaped impressive long-term benefits in updated results from the Spanish METOCARD-CNIC trial.
At 6 months post infarct, the mean left ventricular ejection fraction (LVEF) was significantly higher in the early IV beta-blocker group than in controls. Also, the prevalence of a severely depressed LVEF of 35% or less was significantly lower, as was the proportion of patients having a class I indication for an implantable cardioverter-defibrillator, Dr. Borja Ibanez reported at the annual meeting of the American College of Cardiology.
METOCARD-CNIC was a six-center study in which 270 patients with a first anterior ST-segment elevation myocardial infarction (STEMI), Killip class I or II who presented within 6 hours after symptom onset were randomized to IV metoprolol or no metoprolol administered in the ambulance en route to primary percutaneous coronary intervention (PCI). All subjects were later placed on oral metoprolol, with the first dose coming 12-24 hours after reperfusion, in accord with the American College of Cardiology/American Heart Association 2013 STEMI guidelines, which give oral beta-blocker therapy a class I indication when started within 24 hours of STEMI, noted Dr. Ibanez of San Carlos Hospital, Madrid, and the Carlos III National Center for Cardiovascular Investigations.
The primary study endpoint was infarct size as measured by magnetic resonance imaging 7 days post STEMI. As previously reported, infarct size was 20% smaller in the IV metoprolol recipients (Circulation 2013;128:1495-1503). This finding was encouraging, Dr. Ibanez observed, because infarct size is a major determinant of long-term morbidity and mortality. And while primary PCI for STEMI results in very low acute mortality, there is a high residual risk of subsequent heart failure and death. So the search is on for treatments that reduce infarct size. And prior to METOCARD-CNIC there had been no randomized controlled trials of early IV beta-blocker therapy during the primary PCI era.
At ACC 14, Dr. Ibanez presented prespecified secondary endpoints based upon outcomes at 6 months (see chart) and 2 years post STEMI.
At a median follow-up of 2 years, the composite endpoint comprised of death, reinfarction, hospital admission for heart failure, or malignant arrhythmia had occurred in 10.8% of the IV metoprolol group, compared with 18.3% of controls. This translated to an adjusted 45% relative risk reduction which didn’t quite reach statistical significance, but then again the trial wasn’t of sufficient size to be powered to evaluate clinical endpoints.
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Dr. Borja Ibanez
Of note, the heart failure hospital admission component of the composite endpoint occurred in 2.2% of the IV beta-blocker group, compared with 6.9% of controls, for a 68% relative risk reduction that was statistically significant. The curves began to split at 12 months and continued to diverge through 24 months, according to Dr. Ibanez.
Based upon the encouraging findings of METOCARD-CNIC, planning is underway for a large randomized trial powered to evaluate hard clinical endpoints. It will be called the MOVE ON! trial, the cardiologist added.
METOCARD-CNIC was funded by the Carlos III National Center for Cardiovascular Investigations and the Spanish Ministry of Health and Social Policy. Dr. Ibanez reported having no financial conflicts of interest.