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):1094-104. doi: 10.1056/NEJMoa064247.
Venous thromboembolism is treated with unfractionated heparin or low-molecular-weight heparin, followed by a vitamin K antagonist. We investigated the potential use of idraparinux, a long-acting inhibitor of activated factor X, as a substitute for standard therapy.
We conducted two randomized, open-label noninferiority trials involving 2904 patients with deep-vein thrombosis and 2215 patients with pulmonary embolism to compare the efficacy and safety of idraparinux versus standard therapy. Patients received either subcutaneous idraparinux (2.5 mg once weekly) or a heparin followed by an adjusted-dose vitamin K antagonist for either 3 or 6 months. The primary efficacy outcome was the 3-month incidence of symptomatic recurrent venous thromboembolism (nonfatal or fatal).
In the study of patients with deep venous thrombosis, the incidence of recurrence at day 92 was 2.9% in the idraparinux group as compared with 3.0% in the standard-therapy group (odds ratio, 0.98; 95% confidence interval [CI], 0.63 to 1.50), a result that satisfied the prespecified noninferiority requirement. At 6 months, the hazard ratio for idraparinux was 1.01. The rates of clinically relevant bleeding at day 92 were 4.5% in the idraparinux group and 7.0% in the standard-therapy group (P=0.004). At 6 months, bleeding rates were similar. In the study of patients with pulmonary embolism, the incidence of recurrence at day 92 was 3.4% in the idraparinux group and 1.6% in the standard-therapy group (odds ratio, 2.14; 95% CI, 1.21 to 3.78), a finding that did not meet the noninferiority requirement.
In patients with deep venous thrombosis, once-weekly subcutaneous idraparinux for 3 or 6 months had an efficacy similar to that of heparin plus a vitamin K antagonist. However, in patients with pulmonary embolism, idraparinux was less efficacious than standard therapy. (ClinicalTrials.gov numbers, NCT00067093 [ClinicalTrials.gov] and NCT00062803 [ClinicalTrials.gov].).
静脉血栓栓塞症采用普通肝素或低分子量肝素治疗，随后使用维生素K拮抗剂。我们研究了长效活化因子X抑制剂依达肝素替代标准治疗的潜在用途。
我们进行了两项随机、开放标签的非劣效性试验，涉及2904例深静脉血栓形成患者和2215例肺栓塞患者，以比较依达肝素与标准治疗的疗效和安全性。患者接受皮下注射依达肝素（每周一次，2.5毫克）或肝素，随后使用调整剂量的维生素K拮抗剂，疗程为3个月或6个月。主要疗效结局是有症状的复发性静脉血栓栓塞症（非致命性或致命性）的3个月发生率。
在深静脉血栓形成患者的研究中，依达肝素组第92天的复发率为2.9%，标准治疗组为3.0%（优势比，0.98；95%置信区间[CI]，0.63至1.50），该结果满足预先设定的非劣效性要求。在6个月时，依达肝素的风险比为1.01。依达肝素组第92天临床相关出血率为4.5%，标准治疗组为7.0%（P = 0.004）。在6个月时，出血率相似。在肺栓塞患者的研究中，依达肝素组第92天的复发率为3.4%，标准治疗组为1.6%（优势比，2.14；95%CI，1.21至3.78），这一结果未达到非劣效性要求。
在深静脉血栓形成患者中，皮下注射依达肝素每周一次，持续3个月或6个月，其疗效与肝素加维生素K拮抗剂相似。然而，在肺栓塞患者中，依达肝素的疗效低于标准治疗。（ClinicalTrials.gov编号，NCT00067093[ClinicalTrials.gov]和NCT00062803[ClinicalTrials.gov]。）
