Serebruany Victor L, Malinin Alex I, Hanley Dan F
HeartDrug Research Laboratories, Baltimore, Maryland, USA.
Thromb Haemost. 2008 Jan;99(1):116-20. doi: 10.1160/TH07-09-0563.
Randomized trials showed greater stroke prevention with extended release dipyridamole in combination with low dose aspirin than with either aspirin or dipyridamole alone. However, most studies with this formulation (Aggrenox) were carried out 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. Thirty healthy volunteers (18-40 years old, 15 male and 15 female) of Japanese descent were randomized to Aggrenox (n = 17) or aspirin 81 mg (n = 13 volunteers) for 30 days. Platelet function was assessed at baseline, and on days 15, and 30 by conventional aggregometry, whole blood flow cytometry, and cartridge-based analyzer. 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. The magnitude and durability of platelet response after Aggrenox in healthy Japanese is similar to those effects observed in Caucasians and African-Americans. A larger study to assess drug efficacy and safety in the Japanese post-stroke patients is warranted.
随机试验表明，与单独使用阿司匹林或双嘧达莫相比，缓释双嘧达莫联合低剂量阿司匹林在预防中风方面效果更佳。然而，大多数关于这种制剂（安步乐克）的研究是在欧洲和北美进行的。考虑到药物反应可能存在的种族差异，我们在健康的日本志愿者中开展了一项小型随机研究，以比较不同抗血小板治疗方案对血小板生物标志物变化的影响。30名日本裔健康志愿者（年龄在18至40岁之间，男女各15名）被随机分为两组，分别服用安步乐克（n = 17）或81毫克阿司匹林（n = 13名志愿者），为期30天。在基线期、第15天和第30天，通过传统的血小板聚集测定法、全血流式细胞术和基于试剂盒的分析仪评估血小板功能。安步乐克和阿司匹林在第15天和第30天都能持续抑制血小板。然而，与阿司匹林相比，服用安步乐克进行治疗时，对胶原诱导的血小板聚集的抑制作用更为显著（第15天，p = 0.08），同时封闭时间延长（第30天，p = 0.001）；血小板内皮细胞黏附分子-1（PECAM-1）的表达降低（第30天，p = 0.02），糖蛋白IIb（GPIIb）抗原表达降低（第15天和第30天分别为p = 0.001和0.024），PAC-1抗体检测的GPIIb/IIIa活性降低（p = 0.014和0.03），CD62（P-选择素）降低（第15天和第30天均为p = 0.03），同时与完整的WEDE-15（p = 0.002和0.003）和SPAN-12（p = 0.002和0.04）凝血酶受体相关的蛋白酶激活受体（PAR-1）也受到抑制。健康日本人群服用安步乐克后血小板反应的程度和持久性与白种人和非裔美国人中观察到的效果相似。有必要开展一项更大规模的研究，以评估安步乐克在日本中风后患者中的药物疗效和安全性。
