Objective: To compare efficacy and safety of thromboprophylaxis with semuloparin started postoperatively versus enoxaparin started preoperatively in major abdominal surgery.
Background: 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.
Methods: 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.
Results: 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).
Conclusions: Semuloparin commenced postoperatively did not demonstrate noninferiority to enoxaparin initiated preoperatively for thromboprophylaxis after major abdominal surgery. Study registered with clinicaltrials.gov: NCT00679588.
In this double-blind trial, patients undergoing major abdominal surgery were randomized to daily enoxaparin commenced preoperatively or semuloparin commenced postoperatively for 7 to 10 days. Efficacy (any deep vein thrombosis, nonfatal pulmonary embolism, or all-cause death) and safety (bleeding) were assessed. Semuloparin started postoperatively did not demonstrate noninferiority to enoxaparin started preoperatively.
*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.
Reprints: Ajay K. Kakkar, MBBS, Thrombosis Research Institute, Emmanuel Kaye Building, Manresa Road, Chelsea, London SW3 6LR, UK. E-mail: email@example.com.
The detailed list of members of the SAVE-ABDO group is given in the “Acknowledgement” section.
Disclosure: A.K.K. has received research funding from and has served on advisory boards with Bayer HealthCare, Sanofi-Aventis, Boehringer-Ingelheim, Pfizer Inc, Bristol-Myers Squibb, and Eisai; has been a consultant for Bayer HealthCare, Sanofi-Aventis, Boehringer-Ingelheim, Pfizer Inc, Bristol-Myers Squibb, Eisai, Adventrx, Novartis, Daiichi Sankyo, and Shire Pharmaceuticals; and has received honoraria from Bayer HealthCare, Sanofi-Aventis, Boehringer-Ingelheim, Pfizer Inc, Bristol-Myers Squibb, Eisai, and GlaxoSmithKline. G.A. has had a consultant or advisory role for Bayer and Boehringer-Ingelheim and has received honoraria from Bayer, Boehringer-Ingelheim, GlaxoSmithKline, and Sanofi. W.F. has received honoraria and expenses, and research funding, from Sanofi, Bayer, Pfizer Inc, and Boehringer-Ingelheim. D.G. has had a consultant or advisory role for Astellas, Bayer, Dendreon, Genentech/Roche, Medivation, Novartis, Pfizer Inc, Sanofi, and Viamet; has been on the Speakers Bureau for Dendreon Novartis, Pfizer Inc, and Sanofi; and received research support from Dendreon, Exelixis, GlaxoSmithKline, Janssen, Millennium, Novartis, and Pfizer Inc. M.R.L. has served as a consultant for Astellas Pharma Europe, Bayer HealthCare AG, Bristol-Myers Squibb, Boehringer-Ingelheim, GlaxoSmithKline, Merck Serono, Pfizer Inc, Protola Pharma, and Sanofi. P. Mismetti has served as a member of Steering Committees for Sanofi, GlaxoSmithKline, and Boehringer Ingelheim and has received honoraria from Bayer Healthcare and Pfizer/BMS. P. Mouret has been a consultant for and has received honoraria from Bayer HealthCare, Sanofi, and Bristol-Myers Squibb. J.M. is an employee of Sanofi. F.L. is an employee of Sanofi. A.G.G.T. has served as a consultant for Astellas Pharma Europe, Bayer HealthCare AG, Portola Pharma, and Sanofi. This study was funded by Sanofi.