PLAVIX Clinical Trials
COMMIT (Clopidogrel and Metoprolol in Myocardial Infarction Trial) Trial

COMMIT (ClOpidogrel and Metoprolol in Myocardial Infarction Trial) was a randomized, double-blind, placebo-controlled trial with a 2x2 factorial design. In all, 45,852 patients from 1,250 centers in China presenting within 24 hours of the onset of symptoms of suspected myocardial infarction (MI) with supporting ECG abnormalities (ie, ST elevation, ST depression, or left bundle branch block) were randomized to receive PLAVIX 75 mg once daily or placebo in combination with aspirin (162 mg) until hospital discharge or up to 28 days (mean duration of treatment in survivors: 15 days). Patients undergoing percutaneous coronary intervention (PCI) were excluded from the trial. 19

Inclusion Criteria

  • Suspected MI with supporting ECG changes (ST elevation or depression, or left bundle branch block)
  • Presentation within 24 hours of symptom onset
  • No PCI 11

Efficacy

The COMMIT trial demonstrated that PLAVIX (clopidogrel bisulfate) with aspirin significantly reduced the relative risk of all-cause mortality compared to placebo with aspirin. The co-primary outcome of death from any cause occurred in 7.5% of patients in the PLAVIX plus aspirin group versus 8.1% in the placebo plus aspirin group (P=0.029) during the scheduled treatment period. This represents a 7% reduction in the relative risk of all-cause mortality for patients treated with PLAVIX plus aspirin. 19

Efficacy of PLAVIX + Aspirin vs. Aspirin + Placebo in Reducing the risk of all-cause mortality in STEMI (COMMIT chart)

COMMIT also showed that PLAVIX with aspirin significantly reduced the relative risk of the co-primary combined end point of reinfarction, stroke, or death, compared to placebo with aspirin. The combined outcome occurred in 9.2% of patients in the PLAVIX plus aspirin group versus 10.1% in the placebo plus aspirin group (P=0.002) (Only first relevant events during the scheduled treatment period were counted.) This represents a 9% reduction in the relative risk of death, reinfarction, or stroke for patients treated with PLAVIX plus aspirin compared to those treated with placebo with aspirin.

Safety

COMMIT Safety of PLAVIX + Aspirin vs. Aspirin + Placebo for Patients with Bleeding Events (table)

COMMIT: Major and Minor Bleed in Hospital

The rates for major noncerebral or cerebral bleeding are listed above. A greater number of patients in the PLAVIX group experienced major noncerebral or cerebral bleeding (134 [0.6%] vs. 125 [0.5%], respectively).

Rates for any major noncerebral or cerebral bleeding were not significant. However, clopidogrel was associated with a small but significant rate of other noncerebral bleeding (non-major) and any noncerebral bleeding. Major bleeds are cerebral bleeds or noncerebral bleeds thought to have caused death or that required transfusion.
Indications
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Use PLAVIX plus aspirin for patients with non–ST–segment elevation acute coronary syndrome (UA/non–Q–wave MI), including patients to be managed medically and those to be managed with percutaneous coronary intervention (with or without stent) or CABG, to decrease the rate of a combined end point of CV death, MI, or stroke as well as the rate of a combined end point of CV death, MI, stroke, or refractory ischemia.

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Use PLAVIX plus aspirin for patients with ST–segment elevation acute myocardial infarction to reduce the rate of death from any cause and the rate of a combined end point of death, reinfarction, or stroke. This benefit is not known to pertain to patients who receive primary angioplasty.

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Use PLAVIX alone for patients with a history of recent stroke, recent MI, or established PAD to reduce the rate of a combined end point of new ischemic stroke (fatal or not), new MI (fatal or not), and other vascular death.
Important Risk Information 18
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PLAVIX is contraindicated in patients with active pathologic bleeding such as peptic ulcer or intracranial hemorrhage. PLAVIX should be used with caution in patients who may be at risk of increased bleeding from trauma, surgery, or coadministration with NSAIDs or warfarin. (See CONTRAINDICATIONS and PRECAUTIONS.*)

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The rates of major and minor bleeding were higher in patients treated with PLAVIX plus aspirin compared with placebo
plus aspirin in clinical trials. (See ADVERSE REACTIONS.*)

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As part of the worldwide post–marketing experience with PLAVIX, there have been cases of reported thrombotic thrombocytopenic purpura (TTP), some with fatal outcome. TTP has been reported rarely following use of PLAVIX, sometimes after a short exposure (<2 weeks). TTP is a serious condition that can be fatal and requires urgent treatment including plasmapheresis (plasma exchange). (See WARNINGS.*)

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In clinical trials, the most common clinically important side effects were pruritus, purpura, diarrhea, and rash; infrequent events included intracranial hemorrhage (0.4%) and severe neutropenia (0.05%). (See ADVERSE REACTIONS.*)