Plavix (clopidogrel bisulfate) - 2 indications

Scroll down for information on each indication:

• for the treatment of Acute Coronary Syndrome/Peripheral Arterial Disease; approved November 1997
• for use in patients with ST-segment elevation acute myocardial infarction to reduce the rate of reinfarction or stroke; approved August 2006

General Information

Plavix (clopidogrel bisulfate) is a P2Y12 platelet inhibitor. 

Plavix is specifically indicated for the following:

Acute Coronary Syndrome

• Plavix is indicated to reduce the rate of myocardial infarction (MI) and stroke in patients with non–ST-segment elevation ACS (unstable angina [UA]/non–ST-elevation myocardial infarction [NSTEMI]), including patients who are to be managed medically and those who are to be managed with coronary revascularization. Plavix should be administered in conjunction with aspirin.
• Plavix is indicated to reduce the rate of myocardial infarction and stroke in patients with acute ST-elevation myocardial infarction (STEMI) who are to be managed medically. Plavix should be administered in conjunction with aspirin

Recent MI, Recent Stroke, or Established Peripheral Arterial Disease

• In patients with established peripheral arterial disease or with a history of recent myocardial infarction (MI) or recent stroke, Plavix is indicated to reduce the rate of MI and stroke.

Plavix is supplied as tablets for oral administration. Scroll down for specific dosing/administration recommendations for each indication.

Mechanism of Action

Plavix (clopidogrel) is an inhibitor of platelet activation and aggregation through the irreversible binding of its active metabolite to the P2Y12 class of ADP receptors on platelets.

Side Effects

The most frequent adverse effects associated with the use of Plavix is bleeding, including life-threatening and fatal bleeding. 

The Plavix drug label comes with the following Black Box Warning: The effectiveness of Plavix results from its antiplatelet activity, which is dependent on its conversion to an active metabolite by the cytochrome P450 (CYP) system, principally CYP2C19. Plavix at recommended doses forms less of the active metabolite and so has a reduced effect on platelet activity in patients who are homozygous for nonfunctional alleles of the CYP2C19 gene, (termed “CYP2C19 poor metabolizers”). Tests are available to identify patients who are CYP2C19 poor metabolizers. Consider use of another platelet P2Y12 inhibitor in patients identified as CYP2C19 poor metabolizers.

Indication 1 - Acute Coronary Syndrome/Peripheral Arterial Disease

approved November 1997

Dosing/Administration

In patients who need an antiplatelet effect within hours, initiate Plavix with a single 300 mg oral loading dose and then continue at 75 mg once daily. Initiating Plavix without a loading dose will delay establishment of an antiplatelet effect by several days.

Clinical Trial Results

FDA approval was based on the following studies:

CURE: The CURE study included 12,562 patients with ACS without ST-elevation (UA or NSTEMI) and presenting within 24 hours of onset of the most recent episode of chest pain or symptoms consistent with ischemia. Patients were required to have either ECG changes compatible with new ischemia (without ST-elevation) or elevated cardiac enzymes or troponin I or T to at least twice the upper limit of normal. Patients were randomized to receive Plavix (300 mg loading dose followed by 75 mg once daily) or placebo, and were treated for up to one year. Patients also received aspirin (75-325 mg once daily) and other standard therapies such as heparin. The number of patients experiencing the primary outcome (CV death, MI, or stroke) was 582 (9.3%) in the Plavix-treated group and 719 (11.4%) in the placebo-treated group, a 20% relative risk reduction for the Plavix-treated group. 

COMMIT: In patients with STEMI, the safety and efficacy of Plavix were evaluated in the randomized, placebo-controlled, double-blind study, COMMIT. COMMIT included 45,852 patients presenting within 24 hours of the onset of the symptoms of myocardial infarction with supporting ECG abnormalities (i.e., ST-elevation, ST-depression or left bundle-branch block). Patients were randomized to receive Plavix (75 mg once daily) or placebo, in combination with aspirin (162 mg per day), for 28 days or until hospital discharge, whichever came first. The primary endpoints were death from any cause and the first occurrence of re-infarction, stroke or death. Plavix significantly reduced the relative risk of death from any cause by 7%, and the relative risk of the combination of reinfarction, stroke or death by 9%.

Indication 2 - for patients with STEMI to reduce the rate of MI and Stroke

approved August 2006

Dosing/Administration

The recommended dose is 75 mg once daily orally without a loading dose.

Clinical Trial Results

FDA approval was based on the CAPRIE trial, a 19,185-patient, 304-center, international, randomized, double-blind, parallel-group study comparing Plavix (75 mg daily) to aspirin (325 mg daily). To be eligible to enroll, patients had to have: 1) recent history of myocardial infarction (within 35 days); 2) recent histories of ischemic stroke (within 6 months) with at least a week of residual neurological signs; and/or 3) established peripheral arterial disease (PAD). Patients received randomized treatment for an average of 1.6 years (maximum of 3 years). The trial’s primary outcome was the time to first occurrence of new ischemic stroke (fatal or not), new myocardial infarction (fatal or not), or other vascular death. Deaths not easily attributable to nonvascular causes were all classified as vascular. Plavix was associated with a lower incidence of outcome events, primarily MI. The overall relative risk reduction (9.8% vs 10.6%) was 8.7%. Similar results were obtained when all-cause mortality and all-cause strokes were counted instead of vascular mortality and ischemic strokes (risk reduction 6.9%). In patients who survived an on-study stroke or myocardial infarction, the incidence of subsequent events was lower in the Plavix group.