利伐沙班对高龄老年急性静脉血栓治疗的有效性和安全性研究

Efficiency and safety of rivaroxaban in treatment of acute venous thrombosis in very old patients

目的：对比利伐沙班和华法林对高龄老年急性静脉血栓治疗的有效性和安全性，为利伐沙班用于治疗高龄老年急性静脉血栓提供理论和临床依据。方法入选2012年3月至2014年3月期间解放军总医院经超声检查确诊为急性下肢静脉血栓形成的高龄老年患者82例，年龄（81．5±5．6）岁。随机分为利伐沙班组和华法林组，利伐沙班组39例，先低分子肝素联合利伐沙班，低分子肝素（依诺肝素）1 mg／kg皮下注射，1次／12 h，利伐沙班，10 mg，口服，1次／d，治疗3 d，之后单独口服利伐沙班，10 mg，1次／d；华法林组43例，给予华法林联合低分子肝素治疗，低分子肝素（依诺肝素）1 mg／kg皮下注射，1次／12 h，国际标准化比值（ international normalized ratio ，INR）稳定在1．6～2．5时停用低分子肝素，继续口服华法林，并监测INR。随访观察12个月，定期在解放军总医院行血管超声（上肢动、静脉超声和下肢动、静脉超声）、心脏超声、心电图、胸部CT、脑CT、血常规、血生化等检查，监测治疗前及治疗1，3，6，12个月时血红蛋白、血小板、凝血功能、丙氨酸氨基转移酶（ ALT）和血清肌酐（ SCr ），同时记录试验中发生的主要疗效终点和安全终点。结果两组患者急性血栓均消失，且均未出现新发或再发静脉血栓、肺栓塞和死亡。利伐沙班组在治疗1，3，6，12个月时平均 INR 分别为2.01±0.51、2.02±0.48、2.05±0.52和2.03±0.55，华法林组在治疗1，3，6，12个月时平均INR分别为1.98±0.44、2.04±0.53、2.03±0.49和2.01±0.46。随访观察期间，两组间治疗有效性和安全性差异无统计学意义；血红蛋白、血小板、凝血功能、ALT和SCr在利伐沙班组无显著变化，利伐沙班组和华法林组之间差异无统计学意义（P＞0．05）。结论利伐沙班口服是治疗高龄老年静脉血栓的有效方法，每天口服10 mg是安全有效剂量。利伐沙班疗效与华法林相当，但治疗更简便、依从性更好、安全性更高。

Objective To compare the efficiency and safety of rivaroxaban with those of warfarin in the treatment of acute venous thrombosis in the very old patients , in order to provide theoretical and clinical basis for the former ’ s application .Methods Eighty-two patients （81.5 ±5.6 years old） with ultrasonography-identified acute venous thrombosis in lower extremity treated in Chinese PLA General Hospital from March 2012 to March 2014 were enrolled in the study .They were randomized into rivaroxaban group （ n=39） and warfarin group （n=43）.The rivaroxaban group was given low molecular weight heparin （enoxaparin, 1 mg/kg, subcutaneous injection, once per 12 h） and oral taking of 10 mg rivaroxaban, once per day for the first 3 days, and then followed by rivaroxaban alone at the same dose .The warfarin group was given warfarin plus above dose of low molecular weight heparin for the first several days until international normalized ratio （INR） stably ranged from 1.6 to 2.5, and then followed by oral warfarin with INR monitoring .All enrolled patients were followed up for 12 months.During that period, intravascular ultrasound examination （arteries and veins in upper and lower extremities ） , echocardiography , electrocardiography , chest and brain CT scanning , blood routine test , and blood biochemistry were carried out regularly, and hemoglobin, platelets, coagulation function, alanine aminotransferase （ALT） and serum creatinine （SCr）weremeasuredatbaseline,and1,3,6and12monthsrespectivelyaftertreatment.Primaryefficacyendpointandsafety endpoints＆nbsp;were also observed and recorded .Results Thrombi all disappeared in both rivaroxaban and warfarin groups , and there were no recurrent or new venous thrombosis, pulmonary embolism and deaths in either group .At the 1st, 3rd, 6th and 12th months, the average INR was 2.01 ±0.51, 2.02 ±0.48, 2.05 ±0.52 and 2.03 ±0.55, separately in the rivaroxaban group , and was 1.98 ±0.44, 2.04 ±0.53, 2.03 ±0.49 and 2.01 ±0.46, respectively in the warfarin group .During the follow-up, no significant differences were seen in the efficiency and safety between the 2 groups.Hemoglobin, platelet, coagulation function , ALT and SCr had no significant changes in the 2 groups either.Conclusion Oral administration of rivaroxaban is an effective approach in the treatment of acute venous thrombosis in the very old patients.A dose of daily 10 mg is safety and effective for the treatment .Rivaroxaban has similar efficacy as warfarin , but is safer , more convenient to administer , as well as better compliance .