分站式杂交冠状动脉血运重建术后替格瑞洛和氯吡格雷抗血小板聚集疗效与安全性的比较

Comparison of efficacy and safety of ticagrelor and clopidogrel in antiplatelet aggregation after 2-staged hybrid coronary revascularization

目的比较分站式杂交冠状动脉血运重建术(HCR)后应用替格瑞洛或氯吡格雷抗血小板聚集的疗效与安全性。方法采用前瞻性随机对照研究方法,根据术后抗血小板治疗方案将在我院接受分站式HCR治疗的冠状动脉多支病变患者分为替格瑞洛组(术后予阿司匹林肠溶片100 mg口服、1次/d,替格瑞洛片90 mg口服、2次/d,连续服用1年)与氯吡格雷组(术后予阿司匹林肠溶片100 mg口服、1次/d,硫酸氢氯吡格雷片75 mg、1次/d,连续服用1年)。分析比较2组患者一般情况、手术前后不同时点血小板聚集功能[血小板最大聚集率(MPAR)、P2Y12反应单位(PRU)],术后血小板抑制率[阿司匹林抵抗(AA)、替格瑞洛或氯吡格雷抵抗(ADP)],主要心血管不良事件(MACE)、出血事件和不良反应发生情况。结果纳入本研究的患者共124例,替格瑞洛组和氯吡格雷组各62例,2组患者基线资料(性别、年龄、纽约心脏病协会心功能分级、合并疾病等)的差异均无统计学意义(均P>0.05)。替格瑞洛组和氯吡格雷组术后24 h、7 d、1个月MPAR均低于术前[(50±9)%、(36±8)%、(29±6)%比(65±11)%,均P<0.001;(59±10)%、(47±9)%、(38±7)%比(65±12)%,均P<0.001];替格瑞洛组术后24 h、7 d、1个月MPAR均低于同期氯吡格雷组[(50±9)%比(59±10)%、(36±8)%比(47±9)%、(29±6)%比(38±7)%,均P<0.001]。替格瑞洛组和氯吡格雷组术后24 h、7 d、1个月PRU均低于术前,差异均有统计学意义(均P<0.001);替格瑞洛组术后24 h、7 d、1个月PRU均低于同期氯吡格雷组,差异均有统计学意义(均P<0.001)。2组患者术后24 h AA发生率的差异无统计学意义(P>0.05);替格瑞洛组ADP抑制率高于氯吡格雷组,差异有统计学意义(P<0.001)。随访至第24个月,替格瑞洛组MACE发生率低于氯吡格雷组(11.3%比27.4%,P<0.05)。随访至第12个月,2组出血事件发生率差异无统计学意义(3.2%比8.1%,P>0.05),2组不良反应发生率差异无统计学意义(16.1%比11.3%,P>0.05)。结论分站式HCR术后应用替格瑞洛+阿司匹林较氯吡格雷+阿司匹林能更有效地抑制血小板聚集,减少术后MACE的发生;2种抗血小板聚集治疗方案均未增加出血风险,未出现严重不良反应,均具有较好的安全性。

Objective To compare the efficacy and safety of ticagrelor and clopidogrel in antiplatelet aggregation after 2-staged hybrid coronary revascularization(HCR).Methods A prospective randomized controlled trial was conducted.According to the postoperative antiplatelet therapy scheme,the patients with coronary artery multivessel disease who underwent 2-staged HCR operation in our hospital were divided into ticagrelor group(after the operation,the patients were given aspirin enteric coated tablets 100 mg orally once daily and ticagrelor tablets 90 mg orally twice daily for 1 year)and clopidogrel group(after the operation,the patients were given aspirin enteric coated tablets 100 mg orally once daily and ticagrelor tablets 75 mg orally once daily for 1 year).The general condition,platelet aggregation funtion[maximum platelet aggregation rate(MPAR)and P2Y12 reaction unit(PRU)]at different time points before and after operation,and platelet inhibition rate[aspirin resistance(AA),ticagrelor or clopidogrel resistance(ADP)],major adverse cardiovascular events(MACE),bleeding events,and adverse reactions after operation were analyzed and compared between the 2 groups.Results A total of 124 patients were enrolled in the study,62 patients each in the ticagrelor group and clopidogrel group.There were no statistically significant differences in baseline data(gender,age,New York Heart Association cardiac function classification,concomitant diseases,etc.)between the 2 groups(all P>0.05).The MPARs at 24 h,7 d,and 1 month after operation in the ticagrelor group and clopidogrel group were lower than those before operation[(50±9)%,(36±8)%,(29±6)%vs.(65±11)%and(59±10)%,(47±9)%,(38±7)%vs.(65±12)%,all P<0.001].The MPARs at 24 h,7 d,and 1 month after operation in the ticagrelor group were lower than those in the clopidogrel group[(50±9)%vs.(59±10)%,(36±8)%vs.(47±9)%,(29±6)%vs.(38±7)%,all P<0.001].The PRUs at 24 h,7 d,and 1 month after operation in the 2 groups were lower than those before operation(all P<0.001).The PRUs at 24 h,7 d,and 1 month after operation in the ticagrelor group were lower than those in the clopidogrel group(all P<0.001).There was no significant difference in the incidence of AA 24 hours after operation between the 2 groups(P>0.05);the inhibition rate of ADP in the ticagrelor group was higher than that in the clopidogrel group(P<0.001).At the 24th month of follow-up,the incidence of MACE in the ticagrelor group was lower than that in the clopidogrel group(11.3%vs.27.4%,P<0.05).At the 12th month of follow-up,there was no statistically significant difference in incidence of bleeding events between the 2 groups(3.2%vs.8.1%,P>0.05).There was no statistically significant difference in the incidence of adverse reactions between the 2 groups(16.1%vs.11.3%,P>0.05).Conclusions Compared with clopidogrel+aspirin regimen,tica-grelor+aspirin regimen is more effective in inhibiting platelet aggregation and reducing postoperative MACE after 2-staged HCR.Both antiplatelet aggregation regimens do not increase the risk of bleeding and have no serious adverse reactions.Both regimens have good safety.