*Thrombosis Research Institute and University College London, London, UK †Stroke Unit and Division of Cardiovascular Medicine, Department of Internal Medicine, University of Perugia, Perugia, Italy ‡Department of Orthopaedic Surgery, McGill University Health Centre, Montreal, QC, Canada §Duke University Medical Center, Durham, NC ¶Spine Center Copenhagen, Copenhagen University Hospital, Glostrup, Denmark ‖University of Saint-Étienne, Saint-Étienne, France **Klinikum Frankfurt Höechst, Frankfurt, Germany ††Sanofi, Bridgewater, NJ ‡‡Hamilton Health Sciences General Hospital, McMaster University, Hamilton, ON, Canada.
Ann Surg. 2014 Jun;259(6):1073-9. doi: 10.1097/SLA.0000000000000430.
To compare efficacy and safety of thromboprophylaxis with semuloparin started postoperatively versus enoxaparin started preoperatively in major abdominal surgery.
Venous thromboembolism is an important complication following major abdominal surgery. Semuloparin is a novel ultra-low-molecular-weight heparin with high antifactor Xa and minimal antifactor IIa activity.
In this double-blind noninferiority trial, adult patients undergoing major abdominal or pelvic operation under general anesthesia lasting more than 45 minutes were assigned to either daily enoxaparin 40 mg commenced preoperatively or daily semuloparin 20 mg commenced postoperatively, for 7 to 10 days. Patients underwent bilateral leg venography between 7 and 11 days postsurgery. The primary efficacy end point was the composite of any deep vein thrombosis, nonfatal pulmonary embolism, or all-cause death. The primary safety outcome was bleeding. Both were independently adjudicated.
In total, 4413 patients were randomized; 3030 (1499 in the enoxaparin and 1531 in the semuloparin groups) were evaluable for the primary efficacy end point, which occurred in 97 patients (6.3%) in the semuloparin group and 82 patients (5.5%) in the enoxaparin group [odds ratio (OR) = 1.16, 95% confidence interval (CI): 0.84-1.59]. On the basis of a noninferiority margin of 1.25, postoperative semuloparin did not demonstrate noninferiority to preoperative enoxaparin. Major bleeding occurred in 63 of 2175 patients (2.9%) in the semuloparin group and 98 of 2177 patients (4.5%) in the enoxaparin group (OR = 0.63, 95% CI: 0.46-0.87).
Semuloparin commenced postoperatively did not demonstrate noninferiority to enoxaparin initiated preoperatively for thromboprophylaxis after major abdominal surgery. Study registered with clinicaltrials.gov: NCT00679588.
比较术后即刻开始应用磺达肝素钠与术前即刻开始应用依诺肝素预防大型腹部手术后血栓栓塞的疗效和安全性。
静脉血栓栓塞是大型腹部手术后的一种重要并发症。磺达肝素钠是一种新型超低分子量肝素，具有高抗因子 Xa 和最小抗因子 IIa 活性。
在这项双盲非劣效性试验中，全身麻醉下接受大型腹部或盆腔手术且手术时间超过 45 分钟的成年患者被随机分为每日术前应用依诺肝素 40mg 或术后即刻应用磺达肝素钠 20mg 组，疗程 7 至 10 天。术后 7 至 11 天行双侧下肢静脉造影。主要疗效终点是任何深静脉血栓形成、非致死性肺栓塞或全因死亡的复合终点。主要安全性结局是出血。均由独立评审委员会进行评估。
共纳入 4413 例患者，其中 3030 例（依诺肝素组 1499 例，磺达肝素钠组 1531 例）可评估主要疗效终点，磺达肝素钠组有 97 例（6.3%）和依诺肝素组有 82 例（5.5%）患者发生该终点事件[比值比（OR）=1.16，95%置信区间（CI）：0.841.59]。基于 1.25 的非劣效性边界，术后磺达肝素钠未能证明与术前依诺肝素相比具有非劣效性。磺达肝素钠组有 63 例（2.9%）和依诺肝素组有 98 例（4.5%）患者发生主要出血（OR=0.63，95%CI：0.460.87）。
对于大型腹部手术后的血栓栓塞预防，术后即刻开始应用磺达肝素钠并不优于术前即刻开始应用依诺肝素。该研究已在 clinicaltrials.gov 注册：NCT00679588。
