维吾尔族患者心脏人工瓣膜置换术后个体化抗凝治疗与经验性抗凝治疗疗效的随机对照试验

Individualized anticoagulation versus empirical anticoagulation therapy after cardiac valve replacement in Uygur patients: A randomized controlled trial

目的对比维吾尔族患者人工心脏瓣膜置换术后基于CYP2C9和VKORC1基因的个体化抗凝治疗与经验性抗凝治疗的临床疗效。方法纳入2012年12月至2015年12月新疆医科大学第一附属医院行人工心脏瓣膜置换术的210例维吾尔族患者,术后按随机数字表法进行基因指导下的抗凝[A组106例,女41例、男65例,平均年龄(44.7±10.02)岁]或经验性抗凝治疗[B组104例,女47例、男57例,平均年龄(45.62±10.01)岁]。A组患者检测CYP2C9和VKORC1基因型后基于华法林剂量给药模型抗凝治疗,B组患者给予传统的抗凝治疗,两组均随访1个月,随访期间定期检测患者的凝血功能。结果华法林抗凝治疗4周后国际标准化比值(INR)为1.8~2.5患者百分比A组高于B组(47.1%vs.32.7%,P=0.038)。治疗期间INR≥3.0发生率A组低于B组,但差异无统计学意义(21.6%vs.26.5%,P=0.411)。第一次达到治疗标准INR值所需时间和达到维持剂量所需时间A组短于B组[(8.80±3.07)d vs.(9.26±2.09)d,P=0.031;(14.25±4.55)d vs.(15.33±1.85)d,P=0.032]。出血事件A组1例,B组3例(P=0.293);栓塞事件A组3例,B组5例(P=0.436),两组差异均无统计学意义。结论监测行心脏人工机械瓣膜置换术的维吾尔族患者的CYP2C9和VKORC1基因型后基于华法林剂量给药模型抗凝较经验性抗凝治疗使较多患者的INR值更快地达到目标范围,但两组治疗期间的INR≥3、出血事件及栓塞事件发生率均无明显差异。

Objective To investigate whether the individualized anticoagulation therapy based on CYP2C9 and VKORC 1 gene is superior to empirical anticoagulation therapy after artificial heart valve replacement surgery in Uygur patients. Methods From December 2012 to December 2015, 210 Uygur patients who underwent artificial heart valve replacement surgery at the First Affiliated Hospital of Xinjiang Medical University were randomly assigned to a genetic anticoagulation therapy group （group A, n=106, 41 females and 65 males, aged 44.7±10.02 years） or an empirical anticoagulation therapy group （group B, n=104, 47 females and 57 males, aged 45.62±10.01 years） according to the random number table. CYP2C9 and VKORC1 genotypes were tested in the group A and then wafarin of administration in anticoagulation therapy was recommended. Patients in the group B were treated with conventional anticoagulation. Patients in both groups were followed up for 1 month and coagulation function was regularly tested. Results The percentage of patients with INR values of 1.8-2.5 after 4 weeks warfarin anticoagulation treatment in the group A was higher than that in the group B （47.1% vs. 32.7%, P=0.038）. The rate of INR≥3.0 in the warfarin anticoagulation therapy period in the group A was lower than that in the group B （21.6% vs. 26.5%, P=0.411）. The time to reach the standard INR value and the time to get maintenance dose were shorter in the group A compared with the group B （8.80±3.07 d vs. 9.26±2.09 d, P=0.031; 14.25±4.55 d vs. 15.33±1.85 d , P=0.032）. Bleeding occured in one patient in the group A and three patients in the group B （P=0.293）. Embolic events occured in three patients in the group A and five patients in the group B （P=0.436）. Conclusion Compared with the empirical anticoagulation, the genetic anticoagulation based on wafarin dosing model can spend less time and make more patients to reach the standard INR value. However there is no significant difference between the two groups in the ratio of INR ≥3.0, bleeding and embolic events in the warfarin anticoagulation therapy.