Early-BAMI Trial Fails to Meet Primary Endpoint
April 11, 2016—Findings from the Early-BAMI (Effect of Early Beta-blocker Administration Before Primary Percutaneous Coronary Intervention [PCI] in Patients with ST-Elevation Myocardial Infarction [STEMI]) trial demonstrated that administering intravenous beta blockers before performing a coronary angioplasty in patients who had experienced STEMI was safe, but did not reduce heart attack severity or improve blood flow from the heart’s main pumping chamber.
The study was presented at ACC.16, the American College of Cardiology’s 65th Annual Scientific Session held April 2–4 in Chicago, Illinois. The study was simultaneously published online in the Journal of the American College of Cardiology.
The study’s Lead Investigator, Vincent Roolvink, MD, of Isala Klinieken in Zwolle, The Netherlands, commented in the ACC press release, “In patients with STEMI, beta blockers have been shown to improve survival, reduce the risk of another heart attack, reduce life-threatening arrhythmias, and prevent enlargement of the heart. This was the first large, double-blind, randomized, placebo-controlled trial to assess whether giving intravenous beta blockers before these patients undergo angioplasty would further improve their outcomes. Unfortunately, we showed that it did not.”
In the ACC announcement, Dr. Roolvink noted that results from two previous trials had suggested that giving intravenous beta blockers to STEMI patients before they underwent angioplasty could reduce heart attack severity or improve blood flow from the left ventricle; however, these trials had shortcomings. One had a small enrollment and the other, while larger, was not blinded or placebo-controlled and enrolled only patients whose STEMIs involved the front wall of the left ventricle.
EARLY-BAMI, which was conducted in The Netherlands and Spain, enrolled 683 patients (average age, 62 years; male, 75%) with acute STEMI symptoms of < 12-hours' duration. The patients were randomly assigned to receive the beta blocker metoprolol or a placebo before undergoing angioplasty. The primary endpoint was the severity of the heart attack, as measured by magnetic resonance imaging (MRI) at 30 days. Secondary endpoints were levels of cardiac enzymes and number of occurrences of ventricular arrhythmia. Safety endpoints were symptoms of an abnormally slow heart rate, symptoms of abnormally low blood pressure, and cardiogenic shock.
As summarized in the ACC press release, Dr. Roolvink reported that at 30 days of follow-up, the primary endpoint of average heart attack severity measured by MRI was 15.3% of the left ventricular volume on average in the beta blockers group, compared with 14.9% in the placebo group, a difference that was not statistically significant, nor were there significant differences between the two groups on blood flow from the left ventricle or levels of cardiac enzymes (secondary endpoints). Ventricular arrhythmias occurred in 3.6% of patients who received beta blockers and in 6.9% of those who received a placebo, a difference that met the threshold for statistical significance, but did not result in a clinically significant difference.
Sixteen patients in the beta blockers group experienced symptoms of an abnormally slow heart rate, symptoms of abnormally low blood pressure, or cardiogenic shock, compared with 21 patients in the placebo group, a difference that was not statistically significant.
Dr. Roolvink advised that a limitation of the study is that overall heart attack severity among enrolled patients was lower than expected, which could explain why beta blocker treatment appeared to offer no benefit. Also, although the MRI analyses for the primary endpoint were blinded for both heart rate and study medication, it was not possible to blind physicians and nurses to patients’ heart rate and blood pressure.
Going forward, additional large randomized trials are needed to clarify whether intravenous beta-blocker treatment before angioplasty offers any benefit for STEMI patients, noted the EARLY-BAMI investigators in the ACC announcement.