口服直接凝血酶抑制剂希美加群用于静脉血栓栓塞的二级预防。

Secondary prevention of venous thromboembolism with the oral direct thrombin inhibitor ximelagatran.

作者信息

Schulman Sam, Wåhlander Karin, Lundström Torbjörn, Clason Solveig Billing, Eriksson Henry

机构信息

Coagulation Unit, Department of Medicine, Karolinska Hospital, Stockholm, Sweden.

出版信息

N Engl J Med. 2003 Oct 30;349(18):1713-21. doi: 10.1056/NEJMoa030104.

DOI:10.1056/NEJMoa030104

PMID:14585939

Abstract

BACKGROUND

For many patients with venous thromboembolism, secondary prevention with vitamin K antagonists is not extended beyond six months, since the risk of recurrence may be outweighed by the risk of major bleeding.

METHODS

In a double-blind, multicenter trial, we randomly assigned 1233 patients with venous thromboembolism who had undergone six months of anticoagulant therapy to extended secondary prevention with the oral direct thrombin inhibitor ximelagatran (24 mg) or placebo, taken twice daily, for 18 months without monitoring of coagulation. At base line, bilateral ultrasonography of the legs and perfusion lung scanning were performed.

RESULTS

Data from 612 patients in the ximelagatran group and 611 in the placebo group were analyzed. The occurrence of the primary end point, symptomatic recurrent venous thromboembolism, was confirmed in 12 patients assigned to ximelagatran and 71 patients assigned to placebo (hazard ratio, 0.16; 95 percent confidence interval, 0.09 to 0.30; P<0.001). Death from any cause occurred in 6 patients in the ximelagatran group and 7 patients in the placebo group, and bleeding occurred in 134 patients and 111 patients, respectively (hazard ratio, 1.19; 95 percent confidence interval, 0.93 to 1.53; P=0.17). The incidence of major hemorrhage was low (six events in the ximelagatran group and five in the placebo group), and none of these hemorrhages were fatal. The cumulative risk of a transient elevation of the alanine aminotransferase level to more than three times the upper limit of normal was 6.4 percent in the ximelagatran group, as compared with 1.2 percent in the placebo group (P<0.001).

CONCLUSIONS

Oral ximelagatran was superior to placebo for the extended prevention of venous thromboembolism. There was no significant increase in the frequency of bleeding complications, but there was an increase in the number of patients with a transient elevation in the alanine aminotransferase level.

摘要

背景

对于许多静脉血栓栓塞患者，使用维生素K拮抗剂进行二级预防的时间不会超过6个月，因为复发风险可能会被严重出血风险所抵消。

方法

在一项双盲、多中心试验中，我们将1233例接受了6个月抗凝治疗的静脉血栓栓塞患者随机分配，分别接受口服直接凝血酶抑制剂希美加群（24毫克）或安慰剂进行延长二级预防，每日两次，持续18个月，且无需监测凝血情况。在基线时，对患者进行双侧腿部超声检查和灌注肺扫描。

结果

分析了希美加群组612例患者和安慰剂组611例患者的数据。在分配接受希美加群治疗的患者中有12例、接受安慰剂治疗的患者中有71例出现了主要终点事件，即有症状的复发性静脉血栓栓塞（风险比，0.16；95%置信区间，0.09至0.30；P<0.001）。希美加群组有6例患者、安慰剂组有7例患者死于任何原因，两组分别有134例和111例患者发生出血（风险比，1.19；95%置信区间，0.93至1.53；P=0.17）。严重出血的发生率较低（希美加群组6例事件，安慰剂组5例事件），且这些出血事件均无致命性。希美加群组丙氨酸转氨酶水平短暂升高至正常上限3倍以上的累积风险为6.4%，而安慰剂组为1.2%（P<0.001）。