Peripheral arterial disease ticlopidine

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). 

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... 

Ticlopidine (29) is equally effective in both men and woman and also improves symptoms of claudication in patients with peripheral arterial disease and appears to reduce anginal pain. Patients with subarchnoid haemorrhage and sickle cell disease have shown some improvement with ticlopidine administration. 

Antithrombotic therapy for acute peripheral occlusive disease is largely empirical. Thrombolytic therapy typically is reserved for patients in whom the occlusion is not amenable to surgery and for those in whom a possible delay between the initiation of therapy and thrombolysis would not jeopardize the viability of the limb. Evidence that antithrombotic therapy changes the natural course of the peripheral disease is sparse, but these patients are at an increased risk of cardiovascular mortality and should receive long-term aspirin therapy. Initial trials suggest that ticlopidine may improve the symptoms of chronic arteriosclerotic arterial insufficiency and also reduce fatal and nonfatal cardiovascular events, but further studies are needed. 

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