Am Fam Physician. 2006 Jun 15;73(12):2224-2226.
Beta-blocker therapy has been proven to benefit patients with heart failure, arrhythmias, hypertension, or unstable angina. In some studies, early use of beta blockers has been associated with a 25 percent reduction in mortality rates for one or two days after suspected acute myocardial infarction (MI). The COMMIT (ClOpidogrel and Metoprolol in Myocardial Infarction Trial) Collaborative Group aimed to assess the risks and benefits of adding early intravenous metoprolol (Lopressor) followed by daily oral metoprolol (Toprol XL) to standard therapies for acute MI.
Investigators randomized 45,852 patients who presented to participating Chinese hospitals because of symptoms of acute MI accompanied by left bundle branch block or S-T elevation or depression. Exclusion criteria included patients scheduled for primary coronary intervention and those with contraindications to beta blockers. Participants were assigned randomly to receive intravenous followed by oral administration of metoprolol or identical placebo. The first intravenous injection of 5 mg of metoprolol or placebo was given immediately. If the heart rate was more than 50 beats per minute and the systolic blood pressure was greater than 90 mm Hg after two to three minutes, a second ampule was given. A third ampule could be given if indicated.
Fifteen minutes after the intravenous medication was administered, patients received 50 mg of metoprolol given orally or placebo every six hours for one day. From day 2, patients received 200 mg of controlled-release metoprolol daily for up to four weeks. All other management was at the discretion of physicians. The two primary outcomes were death from any cause and the composite of death, reinfarction, and cardiac arrest during hospitalization or up to day 28. Secondary end points included reinfarction, ventricular fibrillation, cardiac arrest, and cardiogenic shock.
The treatment and control groups were comparable in all major variables. The mean age of participants was 61 years, and 26 percent were 70 years or older. Overall, 28 percent of participants were women. Eight percent of participants had a previous MI, and 43 percent had hypertension. The mean time from onset of symptoms to randomization was 10 hours, with 34 percent of patients randomized within six hours. On study entry, 24 percent had heart failure, 34 percent had systolic blood pressure lower than 120 mm Hg, and 7 percent had tachycardia (110 beats per minute). One half of the patients received fibrinolysis before the study treatment.
Three injections were received by 90 percent of patients allocated to metoprolol and 96 percent of those allocated to placebo. The primary outcomes were not significantly different between the treatment and placebo groups. The 1,774 deaths (7.7 percent) in the metoprolol group were comparable with the 1,797 deaths (7.8 percent) in the control group and corresponded to an odds ratio (OR) of 0.99. Similarly, the composite end point of death, reinfarction, or cardiac arrest occurred in 2,166 (9.4 percent) of the intervention group and 2,261 (9.9 percent) of the control group (OR, 0.96). Further analysis of the cause of death showed that the metoprolol group had a highly significant 22 percent reduction in deaths attributed to arrhythmia but a highly significant 29 percent increase in deaths from cardiogenic shock. The metoprolol group also showed a highly significant 18 percent reduction in any reinfarction and a highly significant 17 percent reduction in ventricular fibrillation during treatment. Conversely, metoprolol was associated with a highly significant 12 percent increase in heart failure and an increase in reported cardiovascular conditions (mainly bradycardia, sinus arrest, or atrial arrhythmia) and respiratory conditions (mainly asthma or bronchospasm).
The authors conclude that the early use of beta blockers in acute MI is associated with a reduced risk of reinfarction and ventricular fibrillation but an increased risk of cardiogenic shock. The risk of cardiogenic shock was greatest during the first day. They advise consideration of beta blocker therapy only when patients are hemodynamically stable following acute MI.
COMMIT Collaborative Group. Early intravenous then oral metoprolol in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet. November 5, 2005;366:1622–32.
Copyright © 2006 by the American Academy of Family Physicians.
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