Pyrazolopyridine Derivative Acts as a Novel Cyclooxygenase Inhibitor: Antiplatelet Effect in Aged Patients with Ischemic Stroke

OBJECTIVE: To examine the antiplatelet effect of a novel pyrazolopyridine derivative (KC-764) in geriatric patients with ischemic stroke. DESIGN: Randomized clinical trial of three graded dose levels. SETTING: A geriatric clinic attached to a nursing home. PATIENTS: Fifteen patients with a history of cerebral infarction with a mean age of 75 +/- 5 years (range, 65-83). Patients were divided into three groups and administered 10, 20, or 40 mg/day KC-764 for 8 weeks. MEASUREMENTS: Platelet aggregation induced by arachidonate, ADP, collagen and platelet-activating factor. Plasma or serum levels of thromboxane B2 and 6-ketoprostaglandin F1 alpha. MAIN RESULTS: Platelet aggregation was inhibited by KC-764 administration and returned to the control level after discontinuation. Although plasma thromboxane B2 levels were markedly decreased, plasma 6-ketoprostaglandin F1 alpha was not affected. However, the dose of 10 mg/day was not sufficient to maintain an effective plasma level of KC-764. There were no side effects or changes in laboratory findings. CONCLUSIONS: We confirmed that KC-764 at a dose of 20 to 40 mg/day is an effective antiplatelet agent and a good candidate for a trial to see if it is feasible for long-term use for the prevention of ischemic stroke in high-risk patients.