小剂量阿司匹林对老年人血小板聚集率的影响和短期安全性评估:一项多中心随机对照临床研究

摘要

目的:观察老年人服用不同剂型阿司匹林50 mg/d或100 mg/d治疗后花生四烯酸诱导的血小板聚集率(AA-Ag)的变化及短期安全性.方法:入选年龄≥ 60岁、经临床评估需服用阿司匹林治疗患者1194例,随机分至阿司匹林肠溶缓释片50 mg/d组(A组)、阿司匹林肠溶缓释片100 mg/d组(B组)和阿司匹林肠溶片100 mg/d组(C组),每组398例.观察治疗(14±3)天后AA-Ag的变化和不良反应,以及(28±3)天的不良反应.对所有符合研究方案,研究期间未服用禁止药物,且完成所有随访内容的病例纳入符合方案集,进行疗效分析;对所有经随机化分组、至少接受一次治疗且具有用药后安全性评价数据的病例,纳入安全性分析集,就安全性指标进行分析.结果:最终1127例受试者完成随访,1017例受试者进入符合方案集,1160例受试者进入安全性分析集.符合方案集中A组(n=347)、B组(n=338)和C组(n=332)治疗后AA-Ag中位数分别为6.65(4.03,10.84)%、5.89 (3.22,10.03)%和6.00(3.68,10.09)%,三组间无统计学差异.随访期间,安全性分析集A组(n=388)、B组(n=387)和C组(n=385)的不良反应主要为轻微出血及胃肠道不良反应,不良反应发生率分别为3.87%、3.36%和7.95%, C组明显高于A组和B组(P<0.05),且未发生心血管事件及严重不良反应;三组出血事件发生率分别为3.09%、2.33%和6.23%,均为轻微出血,C组显著高于A组和B组(P<0.05).结论:老年患者服用阿司匹林50 mg/d及100 mg/d均可明显抑制AA-Ag,短期安全性良好,肠溶缓释剂型较肠溶剂型降低了短期轻微出血及胃肠道不适等不良反应.%Objectives: This study aimed to observe the change of arachidonic acid-induced platelet aggregation rate (AA-Ag) and short-term adverse reactions after taking 50 or 100 mg/d aspirin(enteric-coated sustained-release formulation) or 100 mg/d aspirin (enteric-coated aspirin tablet)in the elderly Chinese population (aged 60 years or older). Methods: A total of 1 194 participants aged 60 or older, who should be recommended to take aspirin therapy due to medical reasons, were recruited and randomly assigned into three groups to receive enteric-coated sustained-release aspirin tablet (50 mg, once daily, group A), or 100 mg, once daily (group B) or enteric-coated aspirin tablet 100 mg once daily (group C), respectively. AA-Ag was measured after (14±3)days of aspirin treatment. Adverse events and bleeding events were recorded during the (28±3)days of follow-up. Results: The AA-Ag in group A (n=347), B (n=338) and C (n=332) post 14-day aspirin therapy were 6.65 (4.03,10.84)%, 5.89(3.22,10.03) % and 6.00(3.68,10.09) %, respectively (P>0.05). During the 28 days follow-up, the adverse events rate of group A (n=388), B (n=387) and C (n=385) was 3.87%,3.36%, and 7.95%, and the mild bleeding events rate was 3.09%, 2.33%, and 6.23%, respectively. Adverse events rate and mild bleeding events rate were significantly higher in group C than in group A and B (P<0.05). Conclusions: Compared with 100 mg-dose aspirin, 50 mg-dose aspirin achieves similar anti-platelet aggregation effect in this elderly Chinese population. The short-term adverse events and mild bleeding risk of aspirin with enteric-coated sustained-release formulation were fewer than that of enteric-coated formulation.