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Efficacy and safety of enoxaparin for preventing venous thromboembolic events after laparoscopic colorectal cancer surgery: a randomized-controlled trial (YCOG 1404)

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Abstract

Purpose

We conducted a prospective study to evaluate the efficacy and safety of postoperative enoxaparin for the prevention of venous thromboembolism (VTE) after laparoscopic surgery for colorectal cancer (LAC) in Japanese patients.

Methods

The subjects of this multicenter, open-label randomized-controlled trial were 121 patients who underwent LAC between September 2015 and May 2017. The patients were randomly allocated to receive intermittent pneumatic compression (IPC) with enoxaparin (20 mg, twice daily), started 24–36 h after surgery and continued until discharge (Enoxaparin group; n = 61), or IPC alone (IPC group; n = 60). The primary endpoint was the incidence of VTE on day 28 after surgery. The safety outcome was the incidence of any bleeding during treatment and follow-up.

Results

The incidence of VTE on day 28 after surgery was 12.3% (7/57 patients) in the enoxaparin group and 11.9% (7/59 patients) in the IPC group ((p = 1.00). One of the 57 patients (1.8%) in the enoxaparin group and none in the IPC group experienced a bleeding event.

Conclusions

It may be unnecessary to give enoxaparin to all Japanese patients for the prevention of VTE after LAC.

The UMIN Clinical Trials Registry number was UMIN000018633.

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References

  1. Donati MB. Cancer and thrombosis. Haemostasis. 1994;24:128–31.

    CAS  PubMed  Google Scholar 

  2. Ambrus JL, Ambrus CM, Mink IB, Pickren JW. Causes of death in cancer patients. J Med. 1975;6:61–4.

    CAS  PubMed  Google Scholar 

  3. Gezelius C, Eriksson A. Neoplastic disease in a medicolegal autopsy material. A retrospective study in northern Sweden. Z Rechtsmed. 1988;101:115–30.

    Article  CAS  PubMed  Google Scholar 

  4. Svendsen E, Karwinski B. Prevalence of pulmonary embolism at necropsy in patients with cancer. J Clin pathol. 1989;42:805–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Tapson VF. Acute pulmonary embolism. N Engl J Med. 2008;358:1037–52.

    Article  CAS  PubMed  Google Scholar 

  6. Sakon M, Maehara Y, Yoshikawa H, Akaza H. Incidence of venous thromboembolism following major abdominal surgery: a multi-center, prospective epidemiological study in Japan. J Thromb Haemost. 2006;4:581–6.

    Article  CAS  PubMed  Google Scholar 

  7. Geerts WH, Heit JA, Clagett GP, Pineo GF, Colwell CW, Anderson FA, et al. Prevention of venous thromboembolism. Chest. 2001;119:132S–75S.

    Article  CAS  PubMed  Google Scholar 

  8. Mismetti P, Laporte S, Darmon JY, Buchmüller A, Decousus H. Meta-analysis of low molecular weight heparin in the prevention of venous thromboembolism in general surgery. Br J Surg. 2001;88:913–30.

    Article  CAS  PubMed  Google Scholar 

  9. Collins R, Scrimgeour A, Yusuf S, Peto R. Reduction in fatal pulmonary embolism and venous thrombosis by perioperative administration of subcutaneous heparin: overview of results of randomized trials in general, orthopedic, and urologic surgery. N Engl J Med. 1988;318:1162–73.

    Article  CAS  PubMed  Google Scholar 

  10. Wille-Jorgensen P, Rasmussen MS, Andersen BR, Borly L. Heparins and mechanical methods for thromboprophylaxis in colorectal surgery. Cochrane Database Syst Rev. 2003;4:001217.

    Google Scholar 

  11. Kerkez MD, Culafic DM, Mijac DD, Rankovic VI, Lekic NS, Stefanovic DZ. A study of pulmonary embolism after abdominal surgery in patients undergoing prophylaxis. World J Gastroenterol. 2009;15:344–8.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Moneta GL, Bedford G, Beach K, Strandness DE. Duplex ultrasound assessment of venous diameters, peak velocities, and flow patterns. J Vasc Surg. 1988;8:286–91.

    Article  CAS  PubMed  Google Scholar 

  13. Nguyen NT, Cronan M, Braley S, Rivers R, Wolfe BM. Duplex ultrasound assessment of femoral venous flow during laparoscopic open gastric bypass. Surg Endosc. 2003;17:285–90.

    Article  CAS  PubMed  Google Scholar 

  14. Nguyen NT, Hinojosa MW, Fayad C, Varela E, Konyalian V, Stamos MJ, et al. Laparoscopic surgery is associated with a lower incidence of venous thromboembolism compared with open surgery. Ann Surg. 2007;246:1021–7.

    Article  PubMed  Google Scholar 

  15. Shapiro R, Vogel JD, Kiran RP. Risk of postoperative venous thromboembolism after laparoscopic and open colorectal surgery: an additional benefit of the minimally invasive approach? Dis Colon Rectum. 2011;54:1496–502.

    Article  PubMed  Google Scholar 

  16. Cimminiello C, Prandoni P, Agnelli G, Di Minno G, Polo Friz H, Scaglione F, et al. Thromboprophylaxis with enoxaparin and direct oral anticoagulants in major orthopedic surgery and acutely ill medical patients: a metaanalysis. Intern Emerg Med. 2017;12:1291–305.

    Article  PubMed  Google Scholar 

  17. Nagata C, Tanabe H, Takakura S, Narui C, Saito M, Yanaihara N, et al. Randomized controlled trial of enoxaparin versus intermittent pneumatic compression for venous thromboembolism prevention in Japanese surgical patients with gynecologic malignancy. J Obstet Gynaecol Res. 2015;41:1440–8.

    Article  CAS  PubMed  Google Scholar 

  18. Hashimoto D, Nakagawa S, Umezaki N, Yamao T, Kitano Y, Yamamura K, et al. Efficacy and safety of postoperative anticoagulation prophylaxis with enoxaparin in patients undergoing pancreatic surgery: a prospective trial and literature review. Pancreatology. 2017;17:464–70.

    Article  CAS  PubMed  Google Scholar 

  19. Dranitsaris G, Jelincic V, Choe Y. Meta-regression analysis to indirectly compare prophylaxis with dalteparin or enoxaparin in patients at high risk for venous thromboembolic events. Clin Appl Thromb Hemost. 2012;18:233–42.

    Article  CAS  PubMed  Google Scholar 

  20. Sakon M, Kobayashi T, Shimazui T. Efficacy and safety of enoxaparin in Japanese patients undergoing curative abdominal or pelvic cancer surgery: results from a multicenter, randomized, open-label study. Thromb Res. 2010;125:e65–70.

    Article  CAS  PubMed  Google Scholar 

  21. Yoshida N, Baba Y, Miyamoto Y, Iwatsuki M, Hiyoshi Y, Ishimoto T, et al. Prophylaxis of postoperative venous thromboembolism using enoxaparin after esophagectomy: a prospective observational study of effectiveness and safety. Ann Surg Oncol. 2018;25:2434–40.

    Article  PubMed  Google Scholar 

  22. Bahl V, Hu HM, Henke PK, Wakefield TW, Campbell DA Jr., Caprini JA. A validation study of a retrospective venous thromboembolism risk scoring method. Ann Surg. 2010;251:344–50.

    Article  PubMed  Google Scholar 

  23. Gould MK, Garcia DA, Wren SM, Karanicolas PJ, Arcelus JI, Heit JA, et al. Prevention of VTE in nonorthopedic surgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-based Clinical Practice Guidelines. Chest. 2012;141:e227S.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. JCS Joint Working Group. Guidelines for the diagnosis, treatment and prevention of pulmonary thromboembolism and deep vein thrombosis (JCS 2009). Circ J. 2011;75:1258–81.

    Article  Google Scholar 

  25. Zaghiyan KN, Sax HC, Miraflor E, Cossman D, Wagner W, Mirocha J, Gewertz B, Fleshner P, Cedars-Sinai DVT Study Group. Timing of chemical thromboprophylaxis and deep vein thrombosis in major colorectal surgery: a randomized clinical trial. Ann Surg. 2016;264:632–9.

    Article  PubMed  Google Scholar 

  26. ENOXACAN Study Group. Efficacy and safety of enoxaparin versus unfractionated heparin for prevention of deep vein thrombosis in elective cancer surgery: a double-blind randomized multicentre trial with venographic assessment. Br J Surg. 1997;84:1099–103.

    Article  Google Scholar 

  27. McLeod RS, Geerts WH, Sniderman KW, Greenwood C, Gregoire RC, Taylor BM, et al. Subcutaneous heparin versus low-molecular-weight heparin as thromboprophylaxis in patients undergoing colorectal surgery: results of the canadian colorectal DVT prophylaxis trial: a randomized, double-blind trial. Ann Surg. 2001;233:438–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Simonneau G, Laporte S, Mismetti P, Derlon A, Samii K, Samama CM, et al. A randomized study comparing the efficacy and safety of nadroparin 2850 IU (0 3 mL) vs enoxaparin 4000 IU (40 mg) in the prevention of venous thromboembolism after colorectal surgery for cancer. J Thromb Haemost. 2006;4:1693–700.

    Article  CAS  PubMed  Google Scholar 

  29. White RH, Zhou H, Murin S, Harvey D. Effect of ethnicity and gender on the incidence of venous thromboembolism in a diverse population in California in 1996. Thromb Haemost. 2005;93:298–305.

    Article  CAS  PubMed  Google Scholar 

  30. Zakai NA, McClure LA. Racial differences in venous thromboembolism. J Thromb Haemost. 2011;9:1877–82.

    Article  CAS  PubMed  Google Scholar 

  31. Surgical Care Improvement Project–Quality Improvement Measure VTE2. https://www.qualitynet.org/dcs/ContentServer?cid=1176726358615&pagename=QnetPublic%2FPage%2FQnetTier3&c=Page. Accessed on 11 Jan 2019.

  32. Rasmussen MS, Jørgensen LN, Wille-Jørgensen P. Prolonged thromboprophylaxis with low molecular weight heparin for abdominal or pelvic surgery. Cochrane Database Syst Rev. 2009;21:CD004318.

    Google Scholar 

  33. Vedovati MC, Becattini C, Rondelli F, Boncompagni M, Camporese G, Balzarotti R, et al. A randomized study on 1-week versus 4-week prophylaxis for venous thromboembolism after laparoscopic surgery for colorectal cancer. Ann Surg. 2014;259:665–9.

    Article  PubMed  Google Scholar 

  34. Verheijen PM, Stevenson AR, Stitz RW, Clark DA, Clark AJ, Lumley JW. Prolonged use of thromboprophylaxis may not be necessary in laparoscopic colorectal surgery. Int J Colorectal Dis. 2011;26:755–9.

    Article  PubMed  Google Scholar 

  35. Cheung HY, Chung CC, Yau KK, Siu WT, Wong SK, Chiu E, et al. Risk of deep vein thrombosis following laparoscopic rectosigmoid cancer resection in Chinese patients. Asian J Surg. 2008;31:63–8.

    Article  PubMed  Google Scholar 

  36. Richardson WS, Apelgren K, Fanelli RD, Earle D. Deep venous thrombosis prophylaxis in laparoscopy: an evidence-based review. Surg Endosc. 2007;21:2335–8.

    Article  PubMed  Google Scholar 

  37. Anderson FA Jr, Spencer FA. Risk factors for venous thromboembolism. Circulation. 2003;107:I9–I16.

    Article  PubMed  Google Scholar 

  38. Baumgartner JM, McKenzie S, Block S, Costantini TW, Lowy AM. Prophylactic enoxaparin doses may be inadequate in patients undergoing abdominal cancer surgery. J Surg Res. 2018;221:183–9.

    Article  CAS  PubMed  Google Scholar 

  39. Fuji T, Ochi T, Niwa S, Fujita S. Prevention of postoperative venous thromboembolism in Japanese patients undergoing total hip or knee arthroplasty: two randomized, double-blind, placebo-controlled studies with three dosage regimens of enoxaparin. J Orthop Sci. 2008;13:442–51.

    Article  CAS  PubMed  Google Scholar 

  40. White RH, McGahan JP, Daschbach MM, Hartling RP. Diagnosis of deep-vein thrombosis using duplex ultrasound. Ann Intern Med. 1989;111:297–304.

    Article  CAS  PubMed  Google Scholar 

  41. Becker DM, Philbrick JT, Abbitt PL. Real-time ultrasonography for the diagnosis of lower extremity deep venous thrombosis. The wave of the future? Arch Intern Med. 1989;149:1731–4.

    Article  CAS  PubMed  Google Scholar 

  42. Cogo A, Lensing AW, Wells P, Prandoni P, Buller HR. Noninvasive objective tests for the diagnosis of clinically suspected deep-vein thrombosis. Haemostasis. 1995;25:27–39.

    CAS  PubMed  Google Scholar 

  43. Guyatt GH, Eikelboom JW, Gould MK, Garcia DA, Crowther M, Murad MH, et al. Approach to outcome measurement in the prevention of thrombosis in surgical and medical patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141:e185S–e194S.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan

    Kazuya Nakagawa, Mitsuyoshi Ota, Yusuke Suwa, Shinsuke Suzuki, Masashi Momiyama, Atsushi Ishibe & Itaru Endo

  2. Department of Surgery, Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, YokohamaYokohama, Kanagawa, 232-0024, Japan

    Jun Watanabe & Chikara Kunisaki

  3. Department of Surgery, Yokosuka Kyosai Hospital, 1-16 Yonegahamadori, Yokosuka, Kanagawa, 238-8558, Japan

    Hirokazu Suwa

  4. Department of Biostatistics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan

    Yusuke Saigusa & Takeharu Yamanaka

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  1. Kazuya Nakagawa
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Correspondence to Jun Watanabe.

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Nakagawa, K., Watanabe, J., Ota, M. et al. Efficacy and safety of enoxaparin for preventing venous thromboembolic events after laparoscopic colorectal cancer surgery: a randomized-controlled trial (YCOG 1404). Surg Today 50, 68–75 (2020). https://doi.org/10.1007/s00595-019-01859-w

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