阿司匹林和氯吡格雷不同服药时间对急性冠状动脉综合征患者血小板聚集率昼夜节律变化的影响

Impact of application time of aspirin and clopidogrel on platelet aggregation in patients with acute coronary syndrome

目的观察急性冠状动脉综合征患者日间、夜间不同时间服用阿司匹林和氯吡格雷对血小板聚集率昼夜变化的影响，确立冠心病患者更有效的服用抗血小板药物时间，提高临床治疗效果。方法采用交叉试验设计，30例急性冠状动脉综合征患者分别设立为日间服药组（日间组）及夜间服药组（夜间组），于药物达稳态浓度后，用全血阻抗法以ADP及花生四烯酸为诱导剂检测24h内5个时间点血小板聚集率。之后，两组交换，药物达稳态浓度后以相同方法再次测定24h内5个时间点血小板聚集率。结果花生四烯酸诱导的血小板聚集率，日间组10：0HD时最高[（7．96±3．64）欧姆]，00：00时最低[（6．12±3．29）欧姆]，两者比较差异无统计学意义（P〉0．05）；夜间组20：00时最高[（7．86±4．28）欧姆]，10：00时最低[（5．46±3．93）欧姆]，两者比较差异有统计学意义（P〈0．05）。ADP诱导的血小板聚集率，日间组10：00时最高[（9．93±5．73）欧姆]，16：00时最低[（9．14±5．13）欧姆]，两者比较差异无统计学意义（P〉0．05）；夜间组20：00时最高[（9．40±5．39）欧姆]，10：00时最低[（7．37±4．12）欧姆]，差异无统计学意义（P〉0．05）。同一时间点两组之间比较，2种诱导剂测定的血小板聚集率在10：00时日间组均明显高于夜间组（P〈0．05），其余4个时间点之间两组比较差异均无统计学意义。结论日间服药与夜间服药血小板聚集率呈现不同的昼夜变化规律，夜间服用阿司匹林及氯吡格雷可抑制晨起血小板聚集高峰，夜间服药优于日间服药。

Objective To observe the impact of various application time of aspirin and clopidogrcl on the circadian rhythm changes of platelet aggregation in patients with acute coronary syndrome. Methods Patients with acute coronary syndrome were divided into day-time （8：00） and night-time （20：00 ） medication group （n = 15 each）. After plasma concentration reached steady state, platelet aggregation was assessed at 5 time points within 24 hours with a mobile four-channel whole blood impedance aggregometer. The platelet aggregation was induced by ADP and arachidonic acid. Thereafter, the two groups were exchanged and platelet aggregation was assessed in the same way post plasma steady state. Results Arachidonic acid-induced platelet aggregation was the highest at 10：00 Am [ （7.96 ± 3.64） ohm] and the lowest at 0：00 [ （6. 12± 3.29） ohm, P 〉 0. 05 ] in day-time group. Platelet aggregation was the highest at 20：00 [ （9.40 ± 5.39） ohm ] and the lowest at 10 ： 00 [ （5.46 ± 3.93 ） ohm ], P 〈 0. 05 ）. ADP- induced platelet aggregation was the highest at 10：00 and the lowest at 16：00 in day-time group （P 〉 0. 05 ） and was the highest at 20：00 and the lowest at 10：00 in night-time group（ P 〉 0. 05 ）. Platelet aggregation induced by two inducers was significantly higher at 10：00 in clay-time group compared to values in night-time group（ all P 〈 0. 05 ）. Conclusion Taking aspirin and clopidogrel at 20：130 was superior to taking the same medications at 8：00 for inhibiting peak platelet aggregation in the morning.