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Clopidogrel Beneficial in Acute MI; ß-Blockers Carry Benefits and Risks

New findings offer strong evidence in favor of including clopidogrel and aspirin in early treatment of acute STEMI, but the value of early beta-blockade depends on whether patients are hemodynamically stable.

A large randomized trial offers new information on the effectiveness of clopidogrel and ß-blockers in the emergency treatment of myocardial infarction. Researchers in China studied more than 45,000 patients who presented within 24 hours of suspected MI. The patients were randomized to receive oral clopidogrel (75 mg immediately and then daily); metoprolol (5–15 mg intravenously, titrated to heart rate >50/min and systolic blood pressure >90 mm Hg, followed by 200 mg/day orally); neither therapy; or both therapies. All patients otherwise received standard treatment, including aspirin. About half of the patients received fibrinolytic therapy, usually before randomization. Ninety-six percent had confirmed MI, 87% had ST-segment elevation on electrocardiography, and 24% had mild-to-moderate heart failure at entry. Endpoints were recorded at hospital discharge or after 28 days of treatment, whichever came first; the effects of clopidogrel and metoprolol were analyzed separately. The study was funded by the manufacturers of both drugs.

Patients who received clopidogrel, compared with those who did not, had significantly lower rates of the composite outcome of death, reinfarction, or stroke (9.2% vs. 10.1%) and all-cause mortality (7.5% vs. 8.1%). These benefits began within the first day of treatment, and patients who took clopidogrel had no significant increase in major bleeding complications compared with those who did not.

Patients who received metoprolol and those who did not had similar rates of the composite outcome of death, reinfarction, or cardiac arrest, but patients who took metoprolol had significantly fewer reinfarctions (2.0% vs. 2.5%), fewer episodes of ventricular fibrillation (2.5% vs. 3.0%), and more episodes of cardiogenic shock (5.0% vs. 3.9%). The groups had similar all-cause mortality rates, but the group that took metoprolol had significantly fewer deaths from arrhythmia (1.7% vs. 2.2%), and significantly more deaths from cardiogenic shock (2.2% vs. 1.7%). Most of the excess risk for shock with metoprolol occurred during the first day of treatment, whereas the decreases in reinfarction and ventricular fibrillation with metoprolol emerged from day 2 onwards. The likelihood of developing shock on metoprolol correlated significantly with baseline risk for shock.

Comment: These findings provide strong evidence in favor of including both aspirin and clopidogrel in early treatment of acute ST-segment–elevation MI. They also suggest that although early ß-blockade can reduce reinfarctions and arrhythmias after STEMI, this therapy might harm patients if it is started before they are clearly hemodynamically stable.

— Bruce Soloway, MD

Published in Journal Watch General Medicine December 16, 2005

Citation(s):

COMMIT (ClOpidogrel and Metoprolol in Myocardial Infarction Trial) Collaborative Group. Addition of clopidogrel to aspirin in 45 852 patients with acute myocardial infarction: Randomised placebo-controlled trial. Lancet 2005 Nov 5; 366:1607-21.

• Medline abstract (Free)

COMMIT (ClOpidogrel and Metoprolol in Myocardial Infarction Trial) Collaborative Group. Early intravenous then oral metoprolol in 45 852 patients with acute myocardial infarction: Randomised placebo-controlled trial. Lancet 2005 Nov 5; 366:1622-32.

• Medline abstract (Free)

Sabatine MS. Something old, something new: ß blockers and clopidogrel in acute myocardial infarction. Lancet 2005 Nov 5; 366:1587-9.

• Medline abstract (Free)

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