PLAVIX Clinical Trials
CLARITY (Clopidogrel as Adjunctive Reperfusion Therapy) Trial

CLARITY (CLopidogrel as Adjunctive ReperfusIon TherapY) was a randomized, double-blind, placebo-controlled trial of 3,491 patients (5% US) from 319 centers in 23 countries presenting within 12 hours of the onset of ST-segment elevation acute myocardial infarction (MI) who were scheduled to receive thrombolytic therapy. Patients were randomized to receive a PLAVIX 300 mg loading dose, followed by PLAVIX 75 mg once daily or placebo up to the day of angiography. Those not receiving angiography received treatment up to day 8 or discharge, whichever came first. All patients received aspirin (150 mg-325 mg on the first day and 75 mg-162 mg/day thereafter). Patients were followed 30 days. 19

Inclusion Criteria 17

  • Suspected ST elevation myocardial infarction and planned for thrombolytic therapy
  • Presentation within 12 hours of symptom onset

Efficacy

CLARITY demonstrated that treatment with PLAVIX plus aspirin was associated with significantly reduced odds of occlusion in the infarct-related artery, death, or recurrent MI before angiography, compared to placebo plus aspirin. The composite outcome of an occluded infarct-related artery (defined as TIMI Flow Grade 0 or 1) on the pre-discharge angiogram, or death, or recurrent MI by the time of the start of angiography, occurred in 15.0% (262/1752) of patients receiving PLAVIX plus aspirin versus 21.7% (377/1739) of patients receiving placebo plus aspirin (P<0.001). This represents a 36% reduction in the odds of experiencing the composite endpoint for the group receiving PLAVIX plus aspirin. In both treatment groups, most of the events accounting for the primary composite outcome were related to occlusion of the infarct-related artery (192/262 for the PLAVIX plus aspirin group and 301/377 for the placebo plus aspirin group). 19

Efficacy of PLAVIX + Aspirin vs. Placebo + Aspirin for reducing odds of occlusion in the infarct-related artery, death, or recurrent myocardial infarction (MI) before angiography in STEMI (CLARITY chart)

Safety

CLARITY-TIMI 28 Safety of Clopidogrel vs. Placebo for bleeding (table)

In CLARITY, the incidence of major bleeding (defined as intracranial bleeding or bleeding associated with a fall in hemoglobin >5 g/dL) was similar between groups (1.3% vs 1.1% in the PLAVIX + aspirin and in the placebo + aspirin groups, respectively). This was consistent across subgroups of patients defined by baseline characteristics, and type of fibrinolytics or heparin therapy. The incidence of fatal bleeding (0.8% versus 0.6% in the PLAVIX + aspirin and in the placebo + aspirin groups, respectively) and intracranial hemorrhage (0.5% vs 0.7%, respectively) was low and similar in both groups.

NOTE:
The TIMI definition for major bleeding included either intracranial hemorrhage or any clinically overt sign of hemorrhage (including via an imaging study) that was associated with a fall in hemoglobin of >5 g/dL (or, when hemoglobin was not available, a fall in hematocrit of >15%). Bleeding episodes with clinically overt, nonintracranial signs of hemorrhage associated with smaller drops in hemoglobin were classified as TIMI minor (3–5 g/dL drop in hemoglobin) and minimal bleeding (<3 g/dL drop). Occurrence of primary intracranial hemorrhage was confirmed using CT, MRI, or autopsy.

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.*)