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ClOpidogrel and Metoprolol in Myocardial Infarction Trial - COMMIT/CCS-2 – Metoprolol
Description:
The goal of the trial was to evaluate treatment with the beta-blocker metoprolol compared with placebo among patients with ST elevation myocardial infarction (MI) also treated with aspirin.
Hypothesis:
Early treatment with the beta-blocker metoprolol will be associated with a reduction in mortality compared with placebo in patients with ST elevation MI.
Study Design
Patients Enrolled: 45,852
Mean Follow Up: Hospital discharge (or through four weeks if still hospitalized)
Female: 28
Patient Populations:
Suspected acute MI, presentation within 24 hours of symptom onset, and ST elevation or left bundle branch block with no clear indication for or contraindication to trial treatment
Exclusions:
Primary percutaneous coronary intervention, high risk of bleeding, shock, systolic blood pressure <100 mm="" hg,="" heart="" rate="">
Primary Endpoints:
1) All-cause mortality by hospital discharge; and 2) all-cause mortality, nonfatal reinfarction, or ventricular fibrillation/arrest by hospital discharge
Drug/Procedures Used:
Patients were randomized to treatment with metoprolol (three intravenous injections of 5 mg each followed by oral 200 mg/day for up to four weeks; n=22,929) or placebo (n=22,923). All patients were also given aspirin 162 mg/day. Patients were also randomized in a factorial design to treatment with clopidogrel or placebo. The trial was conducted exclusively in China.
Principal Findings:
Baseline characteristics were well balanced between the treatment arms, with 67% presenting within 13 hours of symptom onset and 34% within six hours. Fibrinolytic therapy was used in 50% of patients and anticoagulants in 74%. Anterior infarction was present in 50% of patients. The majority of patients had Killip class I on presentation (76%), but a substantial proportion had class II (20%) and III (4%). First intravenous injection of study drug treatment was given in 98.5% of patients in the metoprolol group and 98.7% in the placebo group, and all three injections were given in 90.2% and 96.1%, respectively. Oral treatment was completed in 86.2% and 91.6%, respectively.
There was no difference in the primary endpoint of death, reinfarction, or cardiac arrest by treatment group (9.4% for metoprolol vs. 9.9% for placebo, p=NS). There was also no difference in the co-primary endpoint of all-cause mortality by hospital discharge (7.7% vs. 7.8%, p=NS). Reinfarction was lower in the metoprolol group (2.0% vs. 2.5%, p=0.001). However, ventricular fibrillation occurred more frequently in the metoprolol group (2.5% vs. 3.0%, p=0.001), but there was no difference in other arrests (3.0% vs. 2.8%, p=NS), resulting in no difference in overall cardiac arrest.
Death due to shock occurred more frequently in the metoprolol group (2.2%, n=496 vs. 1.7%, n=384), while death due to arrhythmia occurred less frequently in the metoprolol group (1.7%, n=388 vs. 2.2%, n=498). Cardiogenic shock was higher overall in the metoprolol group (5.0%, n=1,141 vs. 3.9%, n=885; p<0.0001), particularly="" early="" in="" the="" treatment="" period="" (2.1%="" vs.="" 1.4%="" on="" day="" 0)="" and="" among="" patients="" with="" killip="" class="" ii="" (7.9%="" vs.="" 6.5%)="" or="" class="" iii="" (16.2%="" vs.="" 10.4%).="" particularly="" early="" in="" the="" treatment="" period="" (2.1%="" vs.="" 1.4%="" on="" day="" 0)="" and="" among="" patients="" with="" killip="" class="" ii="" (7.9%="" vs.="" 6.5%)="" or="" class="" iii="" (16.2%="" vs.="" 10.4%).="">
Interpretation:
Among patients with ST elevation MI, treatment with metoprolol was not associated with a reduction in the primary endpoints of mortality or death, reinfarction, or cardiac arrest compared with placebo.
Prior studies of beta-blocker therapy in ST elevation MI have demonstrated a reduction in reinfarction, as was observed in the present study. However, cardiogenic shock and death from shock occurred more often in patients treated with metoprolol in COMMIT. Further subgroup analysis demonstrated that those with the highest risk for this treatment-related risk increase were those with poor left ventricular function, as demonstrated by the Killip class subgroup analysis. Additionally, the risk was largest early in the treatment period on days 0 and 1, suggesting intravenous therapy during the acute phase of the infarction should be avoided.
References:
COMMITT Collaborative Group. Addition of clopidogrel to aspirin in 45 852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet 2005; 366: 1622-32.
Presented by Dr. Rory Collins at the March 2005 ACC Annual Scientific Session, Orlando, FL.
Keywords: Thrombolytic Therapy, Infarction, Ventricular Function, Left, Ventricular Fibrillation, Ticlopidine, Heart Arrest, Shock, Cardiogenic, China, Bundle-Branch Block, Metoprolol
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