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Plavix® (clopidogrel bisulfate) Effective Against Atherosclerotic Events

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Plavix® (clopidogrel bisulfate) Effective Against Atherosclerotic Events

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Plavix® (clopidogrel bisulfate) Effective Against Atherosclerotic Events

Plavix® (clopidogrel bisulfate, Bristol-Myers Squibb/Sanofi Pharmaceuticals) is an antiplatelet drug indicated for prevention of atherosclerotic events. It is indicated for use with patients who have had a recent stroke or MI, or for patients with peripheral artery disease.

In a large study called CAPRIE, a randomized, blinded trial of clopidogrel vs. aspirin in patients at risk of ischemic events, Plavix was compared to aspirin for effectiveness and safety in reducing atherosclerotic events. It was found to be modestly superior to aspirin, with less risk of gastrointestinal bleeding or intracranial hemorrhage.1 The outcomes specifically studied were ischemic stroke, MI and other vascular deaths.

The CURE trial—clopidogrel in unstable angina to prevent recurring events—was derived from the CAPRIE study and patients were randomized into two groups: one given Plavix and aspirin, the other aspirin alone. The patients who were on both medications achieved a 20 percent reduction in recurrent cardiovascular events, which is a larger reduction than being on Plavix alone.2 These findings are preliminary.

How the Drug Works
Plavix works by inhibiting ADP-induced platelet aggregation. This effect is irreversible and so the platelet remains "less sticky" for the remainder of its life. Dosed at 75 mg once daily, changes in platelet aggregation are measurable 2 hours after the first dose, with the body reaching a steady state between the third and seventh day of treatment. Conversely, discontinuation of therapy results in normal platelet aggregation returning after about 5 days.

This medicine can be taken without regard to food and is metabolized extensively through the liver. It is one of the lesser metabolites that exerts the antiplatelet activity. The metabolites are excreted almost evenly between the renal and fecal routes. Plavix is highly protein bound. No dosage adjustments were found to be necessary in the geriatric population, those who are renally impaired or according to gender. It is rated category B in pregnancy, and was not studied in nursing mothers or in children.

Precautions: Even though Plavix was found to be safer than aspirin, care must be taken with patients at risk for increased bleeding from trauma, surgery or pathological bleeding conditions such as peptic ulcer. If a patient is scheduled for an invasive procedure, Plavix should be discontinued 7 days prior to the procedure. Caution also should be taken with patients who are on a drug that increases the risk of gastrointestinal bleeding. Because Plavix is metabolized in the liver, patients with severe hepatic dysfunction should be closely monitored.

Plavix is contraindicated in patients who have a hypersensitivity to the drug or who have an active pathological bleed such as a peptic ulcer or intracranial hemorrhage.

Drug Interactions: Interestingly enough, aspirin did not interfere with Plavix's function but did potentiate aspirin's effect on collagen-induced platelet aggregation. For patients on heparin, Plavix did not necessitate changing the dose of heparin. Plavix was not directly studied in concomitant use with warfarin. Of concern is the fact that at high doses in vitro, Plavix inhibited the P450-enzymatic pathway in the liver, so caution must be taken with all drugs that are metabolized via that pathway, such as Dilantin® (phenytoin, Parke-Davis), tamoxifen, tolbutamide, warfarin, torsemide, fluvastatin and many NSAIDs.

Side Effects: The primary concern with Plavix is incidence of hemorrhage--2 percent of patients in the CAPRIE study experienced gastrointestinal bleeding, 0.4 percent experienced intracranial bleeding. Patients were closely monitored during the study for severe neutropenia, as this is a concern with the similar drug Ticlid (ticlopidine, Roche Laboratories). Of 9,586 patients, six experienced this side effect. Though the risk is low, it must be considered in patients on Plavix who present with fever or other signs of infection.

Other gastrointestinal side effects, including abdominal pain, dyspepsia, gastritis and constipation, occurred at a rate of 27 percent. Rash occurred in 15.8 percent of patients taking Plavix.

Patient Education: Teach patients to take Plavix consistently on a once-daily basis, and to inform their health care provider of any other medications they may be taking. Inform them of the increased risk of bleeding, as indicated earlier.

If quick reversal of Plavix's pharmacological effects is necessary, it may be necessary to give a platelet transfusion.


1. CAPRIE Steering Committee (1996, Nov. 16). The Lancet, 348(9038), 1329-1339.

2. Plotsky, J. (2001, March 18). Intervention and atherosclerosis. Presentation at the 50th Annual Scientific Session of the American College of Cardiology.

3. Bristol-Myers Squibb. (revised December 1999). Plavix full prescribing information. New York: Author.

Rebecca Hilgen Bryan is an adult nurse practitioner at Wolfe-Simon Medical Associates, P.A., Cherry Hill, NJ.

Plavix® (clopidogrel bisulfate)

  • Plavix® inhibits platelet aggregation

  • Indicated for the reduction of atherosclerotic events (myocardial infarction, stroke and vascular death) in patients with atherosclerotic disease

  • Dosage is 75 mg once daily

  • Contraindicated in patients with active pathological bleeding such as peptic ulcer or intracranial hemorrhage

  • Can be used with aspirin to further reduce risk of atherosclerotic events; however, concomitant use with aspirin, heparin, NSAIDs such as naproxen and warfarin should be taken with caution

  • Caution should be taken when Plavix is used with any drugs metabolized through the P450 system, such as warfarin, Dilantin® (phenytoin, Parke-Davis), tamoxifen and NSAIDs

  • Works by irreversibly modifying the platelet ADP receptor, with initial inhibition of platelets beginning 2 hours after the first dose and reaching steady state inhibition between 3-7 days

  • No dosage adjustment required for the elderly or renally impaired; Plavix is rated category B for pregnancy and has not been studied in nursing mothers or children

  • Can be taken without regard to food and is extensively metabolized by the liver

  • Patients should be instructed that they might bleed longer with injury and to inform their health care providers that they are taking Plavix prior to any invasive procedures.3


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