达比加群酯联合替格瑞洛对老年心房颤动合并不稳定型心绞痛患者的有效性及安全性研究

Effectiveness and Safety of Dabigatran Combined with Ticagrelor in the Treatment of Elderly Patients with Atrial Fibrillation and Unstable Angina

目的观察达比加群酯联合替格瑞洛对老年心房颤动合并不稳定型心绞痛患者的有效性及安全性。方法选取2015年2月—2017年2月天津医科大学第四中心临床学院收治的100例老年心房颤动合并不稳定型心绞痛患者。将100例老年心房颤动合并不稳定型心绞痛患者随机分为达比加群酯组和华法林组,每组50例。华法林组:在常规治疗基础上加用华法林、替格瑞洛口服。调整华法林剂量维持国际标准化比值(INR)为2.0～3.0。达比加群酯组:在常规治疗基础上加用达比加群酯、替格瑞洛口服。达比加群酯110 mg,2次/d;替格瑞洛90 mg,2次/d。两组均随访1年。分别于治疗前、治疗1、3、12个月测定凝血指标,记录出血事件及心血管不良事件。结果两组凝血酶原时间(PT)、INR、凝血酶时间(TT)、活化部分凝血活酶时间(APTT)、纤维蛋白原(Fib)、D-二聚体比较,差异有统计学意义(P<0.05);不同时间点PT、INR、TT、APTT比较,差异有统计学意义(P<0.05);不同时间点Fib、D-二聚体比较,差异无统计学意义(P>0.05);组别和时间在PT、INR、TT上存在交互作用(P<0.05)。治疗前,两组PT、INR、TT、APTT、Fib、D-二聚体比较,差异无统计学意义(P>0.05);治疗1、3、12个月时,达比加群酯组PT、INR、TT、APTT低于华法林组,Fib、D-二聚体高于华法林组,差异有统计学意义(P<0.05)。随访12个月两组患者心血管事件发生率比较,差异无统计学意义[4.0%(2/50)比6.0%(3/50);χ~2<0.001,P=0.999]。两组患者均未出现严重出血事件。达比加群酯组出血事件总发生率低于华法林组,差异有统计学意义(χ~2=4.955,P=0.026)。结论对于老年心房颤动合并不稳定型心绞痛患者应用达比加群酯联合替格瑞洛能有效预防血栓事件,且与华法林相比具有较低的出血发生率,表明其具有良好的安全性。

Objective To investigate the effectiveness and safety of dabigatran combined with ticagrelor in the treatment of elderly patients with atrial fibrillation and unstable angina but without revascularization.Methods From February 2015 to February 2017,100 elderly patients with atrial fibrillation and unstable angina without revascularization were selected from The Fourth Center Clinical College of Tianjin Medical University.They were randomly divided into dabigatran group(n=50)and warfarin group(n=50),receiving oral administration of dabigatran(110 mg twice daily)combined with ticagrelor(90 mg twice daily),warfarin combined with ticagrelor〔warfarin dose could be adjusted for maintaining an international normalized ratio(INR)of 2.0-3.0〕,respectively,on the basis of the conventional treatment.Both groups were followed up for 1 year.Blood coagulation parameters measured at baseline,at the end of the 1st,3rd,and 12th months of treatment,and bleeding events and cardiovascular adverse events within the follow-up period were recorded.Results There were significant differences in the overall mean values of prothrombin time(PT),INR,thrombin time(TT),activated partial thromboplastin time(APTT),fibrinogen(Fib),D-dimer between the two groups(P<0.05).Mean values of PT,INR,TT,APTT differed significantly between the groups at different time points(P<0.05),but Fib and D-dimer did not(P>0.05).Values of PT,INR and TT were affected by the interactive effect of treatment regimen and treatment duration(P<0.05).The overall mean values of PT,INR,TT,APTT,Fib and D-dimer were similar in both groups at baseline(P>0.05),but after 1,3,and 12 months of treatment,the former 4 increased while the latter two increased significantly in dabigatran group(P<0.05).There was no significant difference in the incidence of cardiovascular adverse events between dabigatran group and warfarin group〔4.0%(2/50)vs 6.0%(3/50);χ2<0.001,P=0.999〕during the follow-up period.No serious bleeding event occurred in both groups,but the incidence of total bleeding events in dabigatran group was lower than that of the warfarin group(χ2=4.955,P=0.026).Conclusion Dabigatran combined with ticagrelor can effectively prevent thrombotic events in elderly patients with atrial fibrillation and unstable angina.Moreover,it has a lower incidence of bleeding events compared with warfarin in combination with ticagrelor,indicating that it has good safety.