Buller Harry R, Cohen Ander T, Davidson Bruce, Decousus Hervé, Gallus Alex S, Gent Michael, Pillion Gerard, Piovella Franco, Prins Martin H, Raskob Gary E
Academic Medical Center, Department of Vascular Medicine, F4-211, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
N Engl J Med. 2007 Sep 13;357(11):1105-12. doi: 10.1056/NEJMoa067703.
The extended use of vitamin K antagonists for prophylaxis against venous thromboembolism is often constrained by risk-benefit limitations and inconvenience. We evaluated the efficacy and safety of a 6-month extension of prophylaxis against recurrent venous thromboembolism with idraparinux in patients who had initially received 6 months of prophylaxis with an anticoagulant.
We randomly assigned patients who had completed 6 months of prophylaxis with idraparinux or a vitamin K antagonist and in whom extended anticoagulation was warranted to receive once-weekly injections of 2.5 mg of idraparinux or placebo for 6 months without monitoring. The primary efficacy and safety outcomes were recurrent venous thromboembolism and major bleeding.
Of 1215 patients, 6 of 594 (1.0%) in the idraparinux group and 23 of 621 (3.7%) in the placebo group had recurrent venous thromboembolism (P=0.002). Major bleeding occurred in 11 patients (1.9%) in the idraparinux group and in none in the placebo group (P<0.001). Of these 11 episodes, 3 were fatal intracranial hemorrhages. As compared with patients whose initial treatment was a vitamin K antagonist, patients whose initial treatment was idraparinux who were assigned to 6 months in the placebo group had a lower incidence of recurrent thromboembolism (0.7% vs. 5.9%); patients who received 6 additional months of idraparinux therapy had a higher incidence of major bleeding (3.1% vs. 0.9%).
During a 6-month extension of thromboprophylaxis, idraparinux was effective in preventing recurrent thromboembolism but was associated with an increased risk of a major hemorrhage. (ClinicalTrials.gov number, NCT00071279 [ClinicalTrials.gov].).
维生素K拮抗剂用于预防静脉血栓栓塞的广泛应用常常受到风险效益限制和不便因素的制约。我们评估了在最初接受6个月抗凝药物预防的患者中，使用依达肝素延长预防复发性静脉血栓栓塞6个月的疗效和安全性。
我们将完成6个月依达肝素或维生素K拮抗剂预防且有必要延长抗凝治疗的患者随机分组，分别接受每周一次皮下注射2.5mg依达肝素或安慰剂，持续6个月，无需监测。主要疗效和安全性结局为复发性静脉血栓栓塞和大出血。
1215例患者中，依达肝素组594例中有6例（1.0%）发生复发性静脉血栓栓塞，安慰剂组621例中有23例（3.7%）发生复发性静脉血栓栓塞（P = 0.002）。依达肝素组有11例患者（1.9%）发生大出血，安慰剂组无大出血发生（P<0.001）。在这11例大出血事件中，3例为致命性颅内出血。与初始治疗为维生素K拮抗剂的患者相比，初始治疗为依达肝素且被分配至安慰剂组6个月的患者复发性血栓栓塞发生率较低（0.7%对5.9%）；继续接受6个月依达肝素治疗的患者大出血发生率较高（3.1%对0.9%）。
在延长6个月的血栓预防期间，依达肝素可有效预防复发性血栓栓塞，但大出血风险增加。（临床试验注册号，NCT00071279 [ClinicalTrials.gov]。）
