Platelet-Active Drugs: The Relationships Among Dose, Effectiveness, and Side Effects. part 28

Мore effective than aspirin in reducing the number of strokes in patients with transient cerebral ischemia or minor stroke, although there was no statistically significant difference in the combined outcome of stroke, MI, or death, it was as effective as aspirin in the treatment of patients with a recent MI, it was more effective than placebo in reducing the risk of the combined outcome of stroke, MI, or vascular death in patients with thromboembolic stroke, it was more effective than conventional antianginal therapy in reducing vascular death or MI in patients with unstable angina, it was more effective than placebo in reducing acute occlusion of coronary bypass grafts, and it was more effective than controls in improving walking distance and reducing vascular complications in patients with peripheral vascular disease. The association of ticlopidine therapy with hypercholesterolemia and neutropenia (occurrence rates: < 1.2 X 10 neutrophils/L, 2.4%; < 0.45 X 10 neutrophils/L, 0.8%), and its comparative expense has reduced enthusiasm for this therapy as an alternative to aspirin in most situations. Ticlopidine therapy also has been associated with thrombocytopenia, aplastic ane-mia, and thrombotic thrombocytopenic purpura (TTP). Ticlopidine has been approved for clinical use in patients with cerebral ischemia when the patient has not responded to therapy with aspirin, when aspirin cannot be tolerated, or when aspirin therapy is contraindicated, although these limitations do not apply to all countries where the drug is registered.

The additive effects of ticlopidine and aspirin have been described in rats, in the inhibition of ADP-induced platelet aggregation ex vivo, in tail-bleeding time prolongation, and in protection from thrombosis in experimental models of platelet-dependent vascular occlusion. The additive antiplatelet effects of aspirin, 40 mg, and ticlopidine, 250 mg, have been reported in healthy volunteers. Several studies have demonstrated the superiority of therapy with ticlopidine and aspirin compared to that with aspirin alone, or aspirin plus warfarin, in preventing thrombotic complications after coronary artery stent placement. Ticlo-pidine has been routinely used in combination with aspirin in patients receiving coronary artery stents, but the better safety profile of clopidogrel has resulted in the replacement of clopidogrel for ticlopidine as the standard antiplatelet regimen after stent deployment. The risk of TTP that is associated with ticlopidine use has been estimated as 0.02% in patients receiving the drug after stent placement. This compares with an incidence of 0.0004% in the general population. The mortality rate for this rare complication exceeds 20%.

The place of ticlopidine in the current therapeutic armamentarium is uncertain, because of the following considerations: (1) the drug is not uniformly cheaper than clopidogrel in different countries; (2) in contrast to clopi-dogrel.

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