Chemical struction of clopidogrel bisulfate

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Clopidogrel

Clopidogrel, which is often prescribed under the brand name Plavix® (clopidogrel bisulfate; produced by Bristol-Myers Squibb and Sanofi-Aventis), is a potent oral antiplatelet agent often used in the treatment of coronary artery disease, peripheral vascular disease, and cerebrovascular disease. more...

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Pharmacology

The mechanism of action of clopidogrel is irreversible blockade of the adenosine diphosphate (ADP) receptor on platelet cell membranes. This receptor is named P2Y12 and is important in platelet aggregation, the cross-linking of platelets by fibrin. The blockade of this receptor inhibits platelet aggregation.

Two hours after a single dose of oral Plavix®, platelet inhibition can be demonstrated.

Pregnancy category

Clopidogrel is pregnancy category B. This means that in animal models, there is no risk of adverse effects in doses equivalent to doses that a pregnant female would ingest. The implication is that the medication is probably safe to administer during human pregnancy. It is currently unknown whether clopidogrel is excreted in human breast milk.

Adverse effects

Serious adverse effects that are associated with clopidogrel include:

Severe neutropenia (Incidence: 5/10,000)
Thrombotic thrombocytopenic purpura (TTP) (Incidence: 4/1,000,000 patients treated)
Hemorrhage - The incidence of hemorrhage may be increased by the co-administration of aspirin.
- Gastrointestinal Hemorrhage (Incidence: 2.0%)
- Cerebral Hemorrhage (Incidence: 0.1 to 0.4%)

Most consensus-based therapeutic guidelines recommend the use of clopidogrel, over aspirin, in patients requiring antiplatelet therapy but with a history of gastric ulceration due to the lower incidence of gastric ulceration associated with the use of clopidogrel vs aspirin. A recent study has shown that in patients with healed aspirin-induced ulcers, however, patients receiving aspirin plus the proton pump inhibitor esomeprazole had a lower incidence of recurrent ulcer bleeding than patients receiving clopidogrel. (Chan et al., 2005)

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Effects of clopidogrel in off-pump beating heart surgery
From CHEST, 10/1/05 by Simon Maltais

PURPOSE: Platelet-rich intracoronary thrombus is central to the pathogenesis of acute coronary syndrome, and patients scheduled for coronary artery bypass graft (CABG) surgery today are receiving more antiplatelet drugs. The use of such drugs, especially the Clopidogrel, before the surgery creates a major dilemma for cardiac surgeons. Our primary objective was to evaluate the role of Clopidogrel on operative bleeding and the timing of discontinuing the medication before surgery. Secondary objectives were to assess the incidence of blood and platelet transfusions following its use.

METHODS: We retrospectively analysed 453 patients undergoing off-pump CABG surgery which received or not Clopidogrel in the last 3 years, looking at the mean operative bleeding (per, post and total) and determining risks factors for blood or platelet transfusions using a multivariate analysis.

RESULTS: Clopidogrel in off-pump CABG surgery is associated with higher operative and post-operative bleeding (702 vs 554 cc, p=0.03 and 864 vs 603 cc, p=0.03). Stopping Clopidogrel 72 hours before surgery significantly reduces mean operative blood loss (554 vs 802 cc, p<0.0001). Patients off Clopidogrel for more than 72 hours don't seem to bleed more than the control group (p=NS). The use of Clopidogrel is associated with more platelet transfusions (OR=11.79, [1.48; 93.86]), but blood transfusions seems similar in all group studied (p=NS).

CONCLUSION: Mean operative blood loss is higher in patients who used Clopidogrel before surgery. Clopidogrel is associated with more platelet, but not blood transfusions after off-pump CABG surgery. Stopping Clopidogrel 72 hours before surgery shows similar mean operative blood loss compared to control group.

CLINICAL IMPLICATIONS: Stopping Clopidogrel 72 hours before surgery shows similar mean operative blood loss compared to control group.

DISCLOSURE: Simon Maltais, None.

Simon Maltais MD * Karine Tetreault MS Quoc-Bao Do MD Notre Dame Hospital, Montreal, PQ, Canada

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