Abstract 2175: Magnitude and Time Course of Platelet Inhibition with Extended Release Dipyridamole with or without Aspirin in Healthy Japanese Volunteers: The AGgrenox versus Aspirin Therapy Evaluation (AGATE-Japan)

Abstract

Background: Randomized trials showed greater stroke prevention with extended release dipyridamole in combination with low dose aspirin than either with aspirin or dipyridamole alone. However, most studies with this formulation (Aggrenox®) were done in Europe and North America. Considering potential inter-racial differences in drug response, we conducted a small randomized study in healthy Japanese volunteers to compare antiplatelet regimens with regard to the changes in the platelet biomarkers. Methods: Thirty healthy volunteers (18–40 years old, 15 male and 15 female) of Japanese descend were randomized to Aggrenox® (n=17) or aspirin 81 mg (n=13 volunteers) for 30 days. Platelet function was assessed at baseline, and days 15, and 30 by conventional aggregometry, whole blood flow cytometry, and cartridge-based analyzer. Results: Both Aggrenox® and aspirin provided sustained platelet inhibition at Day 15 and Day 30. Therapy with Aggrenox®, however, was associated with more prominent and significant inhibition of collagen-induced aggregation (p=0.08, Day 15), as well as prolongation of the closure time (p=0.001, Day 30); diminished expression of platelet endothelial cell adhesion molecule-1 (PECAM-1) (p=0.02, Day 30), glycoprotein IIb (GPIIb) antigen (p=0.001 and 0.024 for Day 15 and Day 30), and GPIIb/IIIa activity by PAC-1 antibody (p = 0.014 and 0.03), CD62 (P-selectin) (p = 0.03 for Day 15 and Day 30), as well as inhibition of protease activated receptors (PAR-1) associated with intact WEDE-15 (p = 0.002 and 0.003) and SPAN-12 (p = 0.002 and 0.04) thrombin receptors when compared with aspirin. Conclusion: The magnitude and durability of platelet response after Aggrenox in healthy Japanese is similar to those effects observed in Caucasians and African-Americans. Larger study to assess drug efficacy and safety in the Japanese post-stroke patients is warranted.