ORLANDO, FLA. — Initiation of β-blocker therapy in the setting of acute MI should generally be delayed for several days, until a patient's condition has stabilized, Rory Collins, M.D., said at the annual meeting of the American College of Cardiology.
Dr. Collins reported the main finding of the β-blocker arm of the Clopidogrel and Metoprolol in Myocardial Infarction Trial/Second Chinese Cardiac Study (COMMIT/CCS-2). In this trial, patients were immediately randomized double-blind to placebo or three doses of 5 mg IV metoprolol within 15 minutes followed by 200 mg/day of oral metoprolol.
The results indicate that optimal use of β-blockers in MI is more complicated than previously appreciated.
Current American College of Cardiology/American Heart Association guidelines, as well as those of the European Society of Cardiology, generally recommend prompt administration of a β-blocker soon after MI onset, unless contraindicated. But COMMIT has shown that the benefits of doing so are essentially cancelled out by increased harm, said Dr. Collins, professor of medicine and epidemiology and codirector of the clinical trial service unit at the University of Oxford (England).
More specifically, in-hospital mortality was 7.7% in patients in the metoprolol arm and 7.8% with placebo. Early therapy resulted in an 18% reduction in the relative risk of in-hospital reinfarction and a 17% reduction in ventricular fibrillation (VF), which translated into a modest absolute reduction in each of these serious adverse events of 5 fewer cases per 1,000 treated patients. But these benefits were entirely offset by a 29% increase in the relative risk of developing cardiogenic shock, which occurred in 3.9% of the placebo patients and 5.0% of those on metoprolol, he continued.
The increased risk of cardiogenic shock in the metoprolol group was seen mostly in the first 24 hours following admission. Moreover, it was largely confined to patients who were Killip class 3 upon presentation.
“We're seeing the excess risk largely in people whose heart function is already compromised. Lowering their heart rate and blood pressure further is just pushing them into shock. It's a negative inotropic effect of β-blockade in someone who's got a failing heart,” Dr. Collins explained.
The merits of long-term oral β-blocker therapy following an MI—reduced reinfarction and mortality—are beyond question. The rationale for studying early β-blockade in COMMIT lies in its uncertain value on top of current standard treatment. When the use of intravenous β-blockers in emergency treatment of MI was studied in more than two dozen trials in the 1970s and 1980s, it did show a moderate benefit; however, those trials mainly enrolled lower-risk patients. As a result of the uncertain efficacy, the use of intravenous β-blockers during acute MI varies widely, from more than 50% of cases in Sweden, to 20% in the United States, and less than 1% in the United Kingdom.
“We know β-blocker therapy is beneficial long-term in people who have heart attack or heart failure. This trial is really telling us when to start, and perhaps how to start—more gradually, more carefully, targeting people when they're stable,” he said.
Discussant Christopher P. Cannon, M.D., said, “we really should think of avoiding IV β-blockade for patients with evidence of compromised left ventricular function, and in those patients … start a β-blocker after a day or two when the patient is stable,” said Dr. Cannon of Brigham and Women's Hospital, Boston.