高龄老年非瓣膜性心房颤动患者应用新型口服抗凝药抗凝治疗有效性及安全性评价研究

Evaluation on effect and safety of anticoagulant therapy with new oral anticoagulant(NOACs) in senile patients with non-valvular atrial fibrillation

目的评价高龄老年(≥80岁)非瓣膜性心房颤动患者应用新型口服抗凝药(NOACs)达比加群、利伐沙班抗凝治疗的有效性及安全性,指导临床用药。方法纳入2014年6月至2016年6月我科室使用华法林、达比加群、利伐沙班抗凝治疗的高龄老年非瓣膜性心房颤动患者各50例,达比加群组使用110 mg,2次/d,利伐沙班组使用10 mg,1次/d,华法林组将国际标准化比值调整至2.0~2.5,比较3组间的出血、栓塞事件的发生率,观察所有患者治疗前、治疗后1个月、3个月、6个月血红蛋白、肝肾功能的变化,观察治疗前及治疗后3 d、1个月、3个月、6个月相关凝血功能指标的变化。结果 (1)华法林组、达比加群组、利伐沙班组组间比较栓塞事件发生率的差异无统计学意义(P>0.05);达比加群组与利伐沙班组出血事件发生率的差异无统计学意义(P>0.05);达比加群组及利伐沙班组的出血事件发生率均低于华法林组且差异有统计学意义(P<0.05)。(2)达比加群组血红蛋白、丙氨酸转氨酶、肌酐等指标用药前后变化差异无统计学意义,活化部分凝血活酶时间(APTT)用药前[(34.25±0.59)s]、用药后3 d[(44.73±2.60)s]升高差异有统计学意义(P<0.05),用药后3 d、1个月、3个月、6个月有升高趋势,但差异无统计学意义(P>0.05),且均未超过正常值上限的2倍;利伐沙班组血红蛋白、丙氨酸转氨酶、肌酐用药前后变化差异无统计学意义,凝血酶原时间(PT)用药前[(14.94±0.31)s]、用药后3 d[(18.05±0.58)s]升高差异有统计学意义(P<0.05),用药后3 d、1个月、3个月、6个月有升高趋势,但差异无统计学意义(P>0.05),且均未超过正常值上限的2倍。结论 (1)高龄老年非瓣膜性心房颤动患者应用NOACs有效性不劣于华法林,安全性优于华法林。(2)使用NOACs无需常规监测凝血功能,但当应用于特殊人群(如高龄老年患者)怀疑出血风险升高或出现轻微出血时,使用达比加群患者将APTT、使用利伐沙班患者将PT血药浓度谷值时升高不超过正常值上限的2倍作为安全性指标之一,且要定期监测肾功能,并在用药前计算肌酐清除率。本次研究样本量较小且随访观察时间短,需增加样本量及观察时间进一步证明上述结论。

Objective To evaluate the effect and safety of the new oral anticoagulant, non-vitamin K antagonist oral anticoagulants（NOACs） in senile patients（≥80 years） with non-valvular atrial fibrillation, and to guide the clinical medication. Methods The senile patients with non-valvular atrial fibrillation, who were treated with Warfarin,Dabigatran etexilate and Rivaroxaban anticoagulant therapy in our department between June 2014 and June 2016,were included in the study（n=50 each）. The Dabigatran etexilate group was treated with 110 mg, twice daily. The Rivaroxaban was treated with 10 mg, once daily. The Warfarin group adjusted the international standard ratio to 2.0-2.5.The incidences of bleeding and thromboembolic events between the three groups were compared. The changes of hemoglobin and liver and kidney function in all patients at baseline and at 1, 3 and 6 months after the treatment were determined. The changes of coagulation function indicators were determined at baseline and at 3 d, 1, 3 and 6 months after the treatment. Results（1）There was no statistically significant difference in the incidence of thromboembolic events between the Warfarin, Dabigatran etexilate and Rivaroxaban groups（P〉0.05）. There was no statistically significant difference in the incidence of bleeding events between the Dabigatran etexilate group and the Rivaroxaban group（P〉0.05）. The incidence of bleeding events in the Dabigatran etexilate group and the Rivaroxaban group was signifi-cantly lower than that in the Warfarin group（P〈0.05）.（2）There were no significant differences in the indicators of hemoglobin, glutamic-pyruvic transaminase and creatinine in the Dabigatran etexilate group before and after the treat-ment. There was statistically significant difference in the increased activated partial thromboplastin time（APTT） at baseline（34.25±0.59）s and at 3 d after the treatment（44.73±2.60）s（P〈0.05）. The APTT showed an increasing trend at3 d, 1, 3 and 6 months after the treatment, and there was no statistical significance（P〉0.05）, which was no more than twice of the upper limit value. There were no significant differences in the hemoglobin, glutamic-pyruvic transaminase and creatinine in the Rivaroxaban group before and after the treatment. There was statistical significance in the in-creased thrombin time（PT） at baseline（14.94 ±0.31）s, and at 3 d after the treatment（18.05 ±0.58）s（P〈0.05）. The PT showed an increasing trend at 3 d, 1, 3 and 6 months after the treatment, and there was no statistical significance（P〉0.05）, which was no more than twice of the upper limit value. Conclusion（1）The effect of using NOACs in senile patients with non-valvular atrial fibrillation is similar as that of Warfarin, whereas its safety is better than that of War-farin.（2）The use of NOACs does not require routine monitoring of coagulation function. When using NOACs in special populations（such as senile patients） suspected with bleeding risk or mild bleeding, the APTT in Dabigatran etexilate group and PT in Rivaroxaban group are no more than twice of the upper limit values, which are considered as the in-dicators for safety. The kidney function should be monitored regularly, and the creatinine clearance rate should be calculated before the treatment. The sample size is small and the follow-up observation time is short in the study. The sample size and observation time should be increased to further prove the above conclusions.