piperidines and Intracranial-Arteriosclerosis

Antiplatelet therapy is the mainstay of the treatment and secondary prevention of cardiovascular and cerebrovascular ischemic events. We assessed the safety, tolerability, and pharmacodynamics of lotrafiban, an oral platelet glycoprotein IIb/IIIa inhibitor, as a secondary prevention strategy in patients with cerebrovascular or cardiovascular disease.. Overall, 451 patients with a recent cardiovascular or cerebrovascular acute ischemic event were randomized in a double-blind fashion to 1 of 5 dosing regimens for 12 weeks: placebo or 5, 20, 50, or 100 mg lotrafiban, both twice daily with 300 to 325 mg/d aspirin. The primary end point was the incidence and tolerability of major and minor bleeding during treatment. Secondary end points included inhibition of platelet aggregation and clinical events. The placebo and lotrafiban 5-mg groups had similarly low rates of minor and major bleeding, but the 100-mg arm was terminated early because of excess major bleeding. Protocol-defined thrombocytopenia (<100 000 platelets/microL) occurred in 5 lotrafiban-treated patients (1.4%, 95% CI 0.2% to 2.7%) and 1 placebo patient (1.1%, 95% CI 0% to 3.1%). Three lotrafiban-treated patients had a nadir platelet count <20 000/microL (0.9%, 95% CI 0% to 1.8%). Lotrafiban produced dose-dependent inhibition of platelet aggregation; 5 mg lotrafiban did not differ significantly from placebo, whereas 100 mg inhibited aggregation by nearly 100%.. -Lotrafiban provides dose-dependent platelet inhibition when administered to a range of patients with atherosclerosis. The level of platelet inhibition appears to correlate with bleeding risk and drug tolerability.

Topics: Administration, Oral; Aged; Benzodiazepines; Coronary Disease; Dose-Response Relationship, Drug; Double-Blind Method; Female; Hemorrhage; Humans; Intracranial Arteriosclerosis; Male; Middle Aged; Piperidines; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Thrombocytopenia; Treatment Outcome

Topics: Adolescent; Adult; Anticonvulsants; Antipsychotic Agents; Bipolar Disorder; Brain Diseases; Cerebrovascular Disorders; Child; Epilepsy; Humans; Hypertension; Hypnotics and Sedatives; Intracranial Arteriosclerosis; Middle Aged; Phenothiazines; Piperidines; Schizophrenia; Seizures

Topics: Aged; Blood Circulation Time; Cerebrovascular Circulation; Cerebrovascular Disorders; Computers; Female; Humans; Intracranial Arteriosclerosis; Male; Middle Aged; Oxygen Consumption; Piperidines; Quinolines; Scintillation Counting; Technetium; Technology, Radiologic; Vasodilator Agents; Vinyl Compounds