Ticlopidine

Antiplatelet therapy reduces risk of ischemic stroke in patients with many different kinds of common cerebrovascular diseases. Ticlopidine was approved initially for patients with threatened stroke who have an intolerance to aspirin. Rothrock and Hart review the efficacy of ticlopidine versus aspirin in the prevention of stroke.

In addition to its antiplatelet properties, ticlopidine reduces plasma fibrinogen levels and increases erythrocyte deformability. The efficacy of ticlopidine has been established in the prevention of coronary artery bypass graft reocclusion, myocardial infarction and death in patients with unstable angina, progressive diabetic retinopathy and major stroke. The recommended dosage is 250 mg twice daily.

Aspirin is an effective, relatively safe and inexpensive antiplatelet agent. Aspirin use results in a 20 to 25 percent reduction in the risk of ischemic stroke following a transient ischemic attack (TIA) or minor stroke. In the Ticlopidine versus Aspirin Stroke Study (TASS), ticlopidine (250 mg twice daily) was found to be superior to aspirin (650 mg twice daily) in patients with a TIA or minor ischemic stroke (absolute reduction of 1 percent). Subgroup data analysis showed that ticlopidine decreased stroke risk in women. The TASS study did not show any advantage of ticlopidine over aspirin in the prevention of myocardial infarction or ischemic disease.

The side effects of ticlopidine are minor except for the 1 percent incidence of severe neutropenia and a similarly low incidence of thrombocytopenia. During the first three months of therapy, complete blood counts, including biweekly platelet counts, will identify these problems. Neutropenia resolves after withdrawal of the drug. Diarrhea occurs in 10 percent of patients and rash in 5 percent.

The combination of aspirin and ticlopidine has not been adequately studied. Laboratory studies show that the effects of these two drugs might be additive, but the clinical value of this conclusion is uncertain.

The authors conclude that ticlopidine should be considered the antithrombotic therapy of choice in patients who cannot tolerate aspirin, or in patients in whom aspirin has failed. Because aspirin and warfarin have documented efficacy in selected patients who are at risk for cardioembolic stroke and since ticlopidine has not been fully assessed, these agents should be used to prevent cardioembolic stroke in this subgroup of patients. The routine use of ticlopidine before aspirin in patients with TIA or minor stroke would result in a modest reduction in stroke incidence, but at a considerably increased cost. If ticlopidine is selected as initial therapy, its use should be reserved for women with hypertension, diabetes mellitus, or both. Given the efficacy of ticlopidine in secondary prevention of stroke and other vascular events in patients with a previous stroke that has resulted in a substantial residual neurologic defect, it is the only alternative for such patients, whether or not aspirin was previously used.

COPYRIGHT 1994 American Academy of Family Physicians
COPYRIGHT 2004 Gale Group