Peripheral arterial disease clopidogrel

Recent Ml or stroke, or established peripheral arterial d/sease For patients with a history of recent Ml, recent stroke, or established peripheral arterial disease, clopidogrel has been shown to reduce the rate of a combined endpoint of new ischemic stroke (fatal or not), new Ml (fatal or not), and other vascular death. 

The CAPRIE trial found that compared to aspirin (325 mg daily), clopidogrel (75 mg daily) was associated with RRR of 8.7% p = 0.043) for the composite endpoint of ischemic stroke, Ml, or vascular death among 19,185 subjects with stroke, MI, or peripheral arterial disease, but no significant reduction in the composite endpoint in the subgroup with stroke (RRR 7.3%, p = 0.26). No comparison of clopidogrel with aspirin in the acute stroke period was performed. Furthermore, stroke as an endoint was not significantly reduced in the stroke patients entered in this trial (RRR 8.0%, p = NS). 

Recent Ml, recent stroke, or established peripheral arterial disease The recommended dose of clopidogrel is 75 mg once daily with or without food. 

Antagonists of the ADP P2Y, 2 receptor, ticlopidine and its safer successor clopidogrel, are also potent inhibitors of platelet aggregation and have demonstrated their efficacy alone and on top of ASA in numerous in clinical studies. The results of the CAPRIE study, a large study involving 19,185 patients with recent Ml, stroke, or established peripheral arterial disease (PAD) demonstrated an 8.7% overall risk reduction versus ASA in the combined endpoints of the first occurrence of Ml, stroke, or other vascular death (30). 

Suboptimal platelet response to clopidogrel may be due to an increased number of platelet P2Y 2 receptors or polymorphism of platelet receptors. Genetic polymorphisms of platelet GPIIb/llla, GPIa/lla, or P2Y 2 receptors have been reported to affect platelet function and may influence dopidogrel response variability (103-105). Recently, it was reported that an increased percentage of patients with peripheral arterial disease have the P2Y 2 receptor H2 haplotype (104). However, in another study, the relation of this haplotype to clopidogrel responsiveness could not be demonstrated (105). Since the relation... 

The efficacy of clopidogrel as an antiplatelet agent in atherothrombotic disorders was demonstrated in the CAPRIE trial. In this study of more than 19,000 patients with a history of either myocardial infarction (MI), stroke, or peripheral arterial disease (PAD), clopidogrel 75 mg/day was compared with aspirin 325 mg/day for its ability to decrease MI, stroke, or cardiovascular death. In the final analysis, clopidogrel was slightly (8% relative risk reduction [RRR]) more effective than aspirin (p =. 043) and had a similar incidence of adverse effects. It is not associated with the blood dyscrasias (neutropenia) common with its congener, ticlopidine, and is used widely in patients with atherosclerosis. 

Ticlopidine and clopidogrel are thienopyridines, which through inhibition of platelet aggregation prolong bleeding time and delay clot retraction. The thienopyridines are prescribed for reduction of myocardial infarction and stroke, for treatment of peripheral arterial disease, and in combination with aspirin for acute coronary syndromes. This latter utility appears to result from the fact that both aspirin and the thienopyridines block major amplification pathways, leading to platelet aggregation... 

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