EARLY-BAMI: No Reduction in Infarct Size With IV Metoprolol Before Primary PCI
CHICAGO, IL—Data from the EARLY-BAMI randomized trial show no reduction in infarct size for STEMI patients who receive IV metoprolol before undergoing PCI.
But when the results were presented today at the American College of Cardiology 2016 Scientific Sessions, several experts said EARLY-BAMI does not provide the final word on upfront IV beta-blockers in the STEMI setting, which had previously shown positive signs in the METOCARD-CNIC trial.
Results also were published online ahead of print in the Journal of the American College of Cardiology.
For the double-blind EARLY-BAMI, Roolvink and colleagues randomized 683 acute STEMI patients within 12 hours of symptom onset to receive IV administration of the beta-blocker metoprolol (two 5-mg bolus doses, with the first given in the ambulance) or placebo prior to undergoing angioplasty. The study was conducted in the Netherlands and Spain.
Infarct size on magnetic resonance imaging (MRI) at 30 days, the study’s primary endpoint, was similar between the metoprolol and placebo groups (mean 15.3% vs 14.9% of LV; P = 0.62).
“Unfortunately, only 55% in both groups actually had their MRIs,” lead author Vincent Roolvink, MD (Isala Klinieken, Zwolle, the Netherlands), pointed out during his presentation. Originally, EARLY-BAMI had enzymatic infarct size based on cardiac troponin T as its primary endpoint but, to reduce the needed study sample and more precisely measure infarct size, researchers switched to MRI.
Neither enzymatic infarct size nor creatinine kinase levels differed by whether patients received IV beta-blockers. LVEF on MRI also was similar.
While the incidence of adverse events also was equivalent between groups, patients receiving metoprolol were less likely than those on placebo to develop malignant arrhythmias (3.6% vs 6.9%; P = 0.050).
Not the Final Answer
One reason why EARLY-BAMI failed to show a reduction in infarct size may be the timing of administration. In the METOCARD-CNIC trial, the patients who derived cardioprotection were the ones given metoprolol further ahead of intervention. EARLY-BAMI, planned before the results of that trial were known, had a shorter window between IV metoprolol and PCI, Roolvink explained during his presentation.
In an editorial accompanying the paper, L. Kristin Newby, MD (Duke University Medical Center, Durham, NC), pointed out that suboptimal MRI use is a notable limitation of EARLY-BAMI. Specifically, she said, “patients who did not undergo MRI were different (older, more often women, and had fewer first contacts at a referring hospital or PCI center) from those who did, which may have resulted in bias in primary endpoint assessment.”
Panelist James B. Hermiller Jr, MD (St. Vincent Heart Center of Indiana, Indianapolis), said during the late-breaking session that the trial doesn’t close the door on IV beta-blockers before primary PCI. Reassuringly, he noted, there was “no safety signal here” with metoprolol in this setting. “Going forward, is this study negative enough that we should drop this? I think not,” Hermiller said, suggesting that other types of beta-blockers might prove effective.
At a later press conference, David E. Kandzari, MD (Piedmont Heart Institute, Atlanta, GA), said that there is “widespread acceptance” of beta-blocker use in patients with ischemic heart disease. But while the drugs are part of the “therapeutic armamentarium” for acute MI patients, there is no specific mandate as to how and when they are given in the United States. “That [such patients] receive such therapy is what is mandated in the clinical guidelines,” Kandzari reported, adding that in-ambulance use of IV beta-blockers is not common practice.
Asked if EARLY-BAMI could in fact spell the end for the approach, Roolvink replied: “No, I think we’re not done yet.”
METOCARD-CNIC, beyond having a longer time between metoprol administration and primary PCI, only included patients with large anterior-wall infarctions and involved doses up to 50 mg. “That still [leaves the discussion open] to see if beta-blockers have any place in the treatment of STEMI patients. I think there’s more room for a large trial including patients at high risk, with large infarct size, [one] giving a higher dose . . . and giving it as soon as possible after diagnosis,” Roolvink said.
- Roolvink V, Ibanez B, Ottervanger JP, et al. Early administration of intravenous beta blockers in patients with ST-elevation myocardial infarction before primary PCI. J Am Coll Cardiol. 2016;Epub ahead of print.
- Newby LK. Intravenous beta-blockers for cardioprotection in STEMI: the saga continues. J Am Coll Cardiol. 2016;Epub ahead of print.
- The study was funded by a research grant from the Dutch Heart Foundation and an unrestricted grant from Medtronic.
- Roolvink reports no relevant conflicts of interest.
- The editorial contains no statement regarding possible conflicts of interest for Newby.
- Intravenous Metoprolol Reduces Infarct Size When Used Early in STEMI Patients
- Beta-Blockers Reduce Long-term Mortality in High-Risk STEMI Patients
- Signs of Cardioprotection Seen in Acute STEMI Patients Receiving IV Beta-blocker Post-PCI