老年冠心病患者经皮冠状动脉介入治疗服用不同剂量替格瑞洛疗效的研究

Research on different ticagrelor dosage in elderly patients undergoing percutaneous coronary intervention

目的观察老年冠心病患者经皮冠状动脉介入治疗(PCI)术后服用替格瑞洛90 mg、每日2次或45 mg、每日2次对腺苷二磷酸(ADP)诱发的血小板聚集率(ADP-Ag)。方法入选2013年12月至2015年12月于北京大学第一医院行PCI治疗的老年冠心病患者48例,年龄(72.48±8.05)岁,比较替格瑞洛90 mg、每日2次(替格瑞洛90 mg组,26例)和替格瑞洛45 mg、每日2次(替格瑞洛45 mg组,22例)。随访12个月,观察主要不良心血管事件和出血事件情况。并对既往服用氯吡格雷75 mg、每日1次更换为替格瑞洛后的ADP-Ag进行比较。结果所有患者服用替格瑞洛治疗4.3(3~7)d后均在清晨空腹服药前抽血检测ADP-Ag谷值,替格瑞洛90 mg组ADP-Ag平均为(27.88±7.77)%,替格瑞洛45 mg组为(37.87±2.90)%,两组比较差异有统计学意义(P=0.039)。替格瑞洛90 mg组12例检测服用替格瑞洛2 h后的ADP-Ag峰值,平均为(19.02±9.52)%;替格瑞洛45 mg组有7例检测了服用替格瑞洛2 h后的ADP-Ag峰值,平均为(27.74±5.09)%,两组比较差异有统计学意义(P=0.041)。21例患者氯吡格雷75 mg、每日1次转换为替格瑞洛90 mg、每日2次时,转化前后ADP-Ag比较差异有统计学意义[(51.70±5.24)%比(26.87±7.33)%,P=0.027]。15例患者氯吡格雷75 mg、每日1次转换为替格瑞洛45 mg、每日2次时,转化前后ADP-Ag比较差异有统计学意义[(47.98±5.39)%比(38.29±2.65)%,P=0.034]。既往氯吡格雷75 mg、每日1次ADP-Ag[(51.18±5.55)%比(64.41±3.03)%,P=0.045],替格瑞洛45 mg、每日2次[(37.87±2.90)%比(64.41±3.03)%,P=0.028],替格瑞洛90mg、每日2次[(27.88±7.77)%比(64.41±3.03)%,P=0.023]均显著低于既往未服用P2Y12受体抑制剂时,差异均有统计学意义。替格瑞洛45mg、每日2次ADP-Ag[(37.87±2.90)%比(51.18±5.55)%,P=0.035],替格瑞洛90 mg、每日2次[(27.88±7.77)%比(51.18±5.55)%,P=0.030]显著低于既往氯吡格雷75 mg、每日1次时,差异有统计学意义。替格瑞洛45 mg、每日2次ADP-Ag与替格瑞洛90mg、每日2次比较[(37.87±2.90)%比(27.88±7.77)%,P=0.039],差异有统计学意义。结论替格瑞洛90 mg、每日2次和45 mg、每日2次对血小板聚集的抑制作用优于氯吡格雷75 mg、每日1次;老年冠心病患者PCI术后使用替格瑞洛45 mg、每日2次安全有效,出血风险降低,心血管事件发生率未增加。

Objective To investigate ADP-induced platelet aggregation rate （ADP-Ag）, safety and efficacy of different ticagrelor dosage in elderly patients undergoing PCI. Methods 48 elderlypatients aged 60 or older were enrolled. After PCI treatment, the patients received antiplatelet therapy with ticagrelor 90 mg（n=26）or 45 mg （n=22）twice daily. ADP-Ag was measured on day 3 to 7 after initial ticagrelor therapy and compared between the two different-dose ticagrelor groups. ADP-Ag ticagrelor treatment was also compared to measurement if patients were previously taking clopidogrel 75 mg daily. Major adverse cardiovascular events （MACE）and bleeding events were recorded in following 12 months. Results Inhibition of ADP-induced platelet aggregation was greater for ticagrelor 90 mg BID versus 45 mg BID（ADP-Ag （27.88±7.77）% vs. （37.87±2.90）%,P〈0.05）. During the follow-up period, no gastrointestinal bleedings, cerebral hemorrhage or thrombus events occurred in all patients. In ticagrelor 90 mg BID group, stent-restenosis occurred in 3 patients and they needed to take revascularization therapy. Minimal bleeding events occurred in 4 patients （15.4% ） and 1 patient （4.5%） with ticagrelor 90 mg and 45 mg BID treatment, respectively. The ADP-Ag with clopidogrel 75 mg QD treatment previously was （51.18±5.55） %, and declined to （26.87±7.33） % and （38.29±2.65） % after conversion to ticagrelor 90 mg BID and 45 mg BID treatment, respectively. Conclusions Ticagrelor of 90 mg BID or 45 mg BID both inhibited ADP-induced platelet aggregation better than clopidogrel. Ticagrelor 45 mg BID was not inferior to 90 mg BID in preventing MACE and with less minimal bleeding events in elderly patients undergoing PCI.