Division of Internal and Cardiovascular Medicine and Stroke Unit, Department of Internal Medicine, University of Perugia, Perugia, Italy.
N Engl J Med. 2012 Feb 16;366(7):601-9. doi: 10.1056/NEJMoa1108898.
Patients receiving chemotherapy for cancer are at increased risk for venous thromboembolism. Limited data support the clinical benefit of antithrombotic prophylaxis.
In this double-blind, multicenter trial, we evaluated the efficacy and safety of the ultra-low-molecular-weight heparin semuloparin for prevention of venous thromboembolism in patients receiving chemotherapy for cancer. Patients with metastatic or locally advanced solid tumors who were beginning to receive a course of chemotherapy were randomly assigned to receive subcutaneous semuloparin, 20 mg once daily, or placebo until there was a change of chemotherapy regimen. The primary efficacy outcome was the composite of any symptomatic deep-vein thrombosis, any nonfatal pulmonary embolism, and death related to venous thromboembolism. Clinically relevant bleeding (major and nonmajor) was the main safety outcome.
The median treatment duration was 3.5 months. Venous thromboembolism occurred in 20 of 1608 patients (1.2%) receiving semuloparin, as compared with 55 of 1604 (3.4%) receiving placebo (hazard ratio, 0.36; 95% confidence interval [CI], 0.21 to 0.60; P<0.001), with consistent efficacy among subgroups defined according to the origin and stage of cancer and the baseline risk of venous thromboembolism. The incidence of clinically relevant bleeding was 2.8% and 2.0% in the semuloparin and placebo groups, respectively (hazard ratio, 1.40; 95% CI, 0.89 to 2.21). Major bleeding occurred in 19 of 1589 patients (1.2%) receiving semuloparin and 18 of 1583 (1.1%) receiving placebo (hazard ratio, 1.05; 95% CI, 0.55 to 1.99). Incidences of all other adverse events were similar in the two study groups.
Semuloparin reduces the incidence of thromboembolic events in patients receiving chemotherapy for cancer, with no apparent increase in major bleeding. (Funded by Sanofi; ClinicalTrials.gov number, NCT00694382.).
接受癌症化疗的患者发生静脉血栓栓塞的风险增加。有限的数据支持抗血栓形成预防的临床获益。
在这项双盲、多中心试验中，我们评估了超低分子量肝素 semuloparin 预防接受癌症化疗的患者静脉血栓栓塞的疗效和安全性。正在开始接受化疗疗程的转移性或局部晚期实体瘤患者被随机分配接受皮下 semuloparin，每日 20mg，或安慰剂，直到化疗方案改变。主要疗效终点是任何症状性深静脉血栓形成、任何非致命性肺栓塞和与静脉血栓栓塞相关的死亡的复合终点。临床上相关的出血（主要和非主要）是主要的安全性结局。
中位治疗持续时间为 3.5 个月。接受 semuloparin 治疗的 1608 例患者中有 20 例（1.2%）发生静脉血栓栓塞，而接受安慰剂治疗的 1604 例患者中有 55 例（3.4%）（风险比，0.36；95%置信区间[CI]，0.21 至 0.60；P<0.001），按癌症的起源和分期以及静脉血栓栓塞的基线风险定义的亚组中疗效一致。接受 semuloparin 和安慰剂治疗的患者中，临床上相关出血的发生率分别为 2.8%和 2.0%（风险比，1.40；95%CI，0.89 至 2.21）。接受 semuloparin 治疗的 1589 例患者中有 19 例（1.2%）和接受安慰剂治疗的 1583 例患者中有 18 例（1.1%）发生主要出血（风险比，1.05；95%CI，0.55 至 1.99）。两组研究中其他所有不良事件的发生率相似。
Semuloparin 可降低接受癌症化疗患者的血栓栓塞事件发生率，且主要出血无明显增加。（由 Sanofi 资助；ClinicalTrials.gov 编号，NCT00694382）。
