Skip to main content

Advertisement

SpringerLink
Log in

Direct oral anticoagulants (DOACs) versus low-molecular-weight heparin (LMWH) for extended thromboprophylaxis following major abdominal/pelvic cancer-related surgery: a systematic review and meta-analysis

  • Review Article
  • Published:
Surgical Endoscopy Aims and scope Submit manuscript

Abstract

Background

The use of direct oral anticoagulants (DOACs) as an alternative to low-molecular-weight heparin (LMWH) for extended thromboprophylaxis of abdominal/pelvic cancer-related postoperative thromboembolism (VTE) is unclear. We aim to investigate the efficacy and safety of DOACs vs. LMWH in these patients.

Methods

A systematic review was conducted using EMBASE, MEDLINE, CENTRAL, and Web of science through May 19th, 2023 for all randomized controlled trials (RCTs) and observational studies that compared the outcomes with DOACs vs. LMWH for extended thromboprophylaxis among patients undergoing abdominal/pelvic cancer surgery. Primary efficacy outcome was clinical VTE, and safety outcome was clinically relevant bleeding complications reported within the 30-day postoperative period. This study was registered in PROSPERO (CRD42023413175).

Results

We identified 5078 articles and selected 29 full-text articles for eligibility. A total of 9 studies (2 RCTs and 7 observational studies) encompassing 2651 patients were included for systematic review and 7 for meta-analysis. When compared with LMWH extended thromboprophylaxis, DOACs had a similar incidence of VTE (RR: 0.65 [95% CI: 0.32–1.33], I2 = 0%), major bleeding (RR: 1.68 [95% CI: 0.36–7.9], I2 = 26%), and clinically relevant non-major bleeding (RR: 0.68 [95% CI: 0.39–1.19], I2 = 0%). Subgroup analysis suggested no difference according to the study type (RCTs versus observational studies) regarding clinical VTE or major bleeding (Pinteraction = 0.43 and Pinteraction = 0.71, respectively).

Conclusion

Our results suggest that DOACs for extended thromboprophylaxis were an effective and safe alternative to LMWH after major abdominal/pelvic cancer-related surgery.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Serrano PE, Parpia S, Linkins LA, Elit L, Simunovic M, Ruo L, Bhandari M, Levine M (2018) Venous thromboembolic events following major pelvic and abdominal surgeries for cancer: a prospective cohort study. Ann Surg Oncol 25(11):3214–3221. https://doi.org/10.1245/s10434-018-6671-7

    Article  PubMed  Google Scholar 

  2. Farge D, Frere C, Connors JM, Khorana AA, Kakkar A, Ay C, Muñoz A, Brenner B, Prata PH, Brilhante D, Antic D, Casais P, Guillermo Esposito MC, Ikezoe T, Abutalib SA, Meillon-García LA, Bounameaux H, Pabinger I, Douketis J (2022) 2022 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer, including patients with COVID-19. Lancet Oncol 23(7):e334–e347. https://doi.org/10.1016/S1470-2045(22)00160-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Lyman GH, Carrier M, Ay C, Di Nisio M, Hicks LK, Khorana AA, Leavitt AD, Lee AYY, Macbeth F, Morgan RL, Noble S, Sexton EA, Stenehjem D, Wiercioch W, Kahale LA, Alonso-Coello P (2021) American Society of Hematology 2021 guidelines for management of venous thromboembolism: prevention and treatment in patients with cancer. Blood Adv 5(4):927–974. https://doi.org/10.1182/bloodadvances.2020003442

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Falanga A, Ay C, Di Nisio M, Gerotziafas G, Jara-Palomares L, Langer F, Lecumberri R, Mandala M, Maraveyas A, Pabinger I, Sinn M, Syrigos K, Young A, Jordan K (2023) Venous thromboembolism in cancer patients: ESMO Clinical Practice Guideline. Ann Oncol 34(5):452–467. https://doi.org/10.1016/j.annonc.2022.12.014

    Article  CAS  PubMed  Google Scholar 

  5. Felder S, Rasmussen MS, King R, Sklow B, Kwaan M, Madoff R, Jensen C (2019) Prolonged thromboprophylaxis with low molecular weight heparin for abdominal or pelvic surgery. Cochrane Database Syst Rev 8(8):Cd004318. https://doi.org/10.1002/14651858.CD004318.pub5

    Article  PubMed  Google Scholar 

  6. Knoll W, Fergusson N, Ivankovic V, Wang T-F, Caiano L, Auer R, Carrier M (2021) Extended thromboprophylaxis following major abdominal/pelvic cancer-related surgery: a systematic review and meta-analysis of the literature. Thrombosis Res 204:114–122. https://doi.org/10.1016/j.thromres.2021.06.010

    Article  CAS  Google Scholar 

  7. Ross ME, Glickman A, Brennecke A, Tayebnejad A, Guntupalli SR (2020) Adherence to postoperative thromboprophylactic medication among gynecologic oncology patients: a subanalysis. Gynecol Oncol 158(3):754–759. https://doi.org/10.1016/j.ygyno.2020.06.505

    Article  CAS  PubMed  Google Scholar 

  8. Guntupalli SR, Brennecke A, Behbakht K, Tayebnejad A, Breed CA, Babayan LM, Cheng G, Ramzan AA, Wheeler LJ, Corr BR et al (2020) Safety and efficacy of apixaban vs enoxaparin for preventing postoperative venous thromboembolism in women undergoing surgery for gynecologic malignant neoplasm: a randomized clinical trial. JAMA Network Open 3(6):e207410. https://doi.org/10.1001/jamanetworkopen.2020.7410

    Article  PubMed  PubMed Central  Google Scholar 

  9. Longo de Oliveira ALM, de Oliveira Pereira RF, Agati LB, Ribeiro CM, Kawamura Suguiura GY, Cioni CH, Bermudez M, Pirani MB, Caffaro RA, Castelli V, Resende Aguiar VC, Volpiani GG, Paschoa A, Scarlatelli Macedo AV, de Barros e Silva PGM, de Campos Guerra JC, Fareed J, Lopes RD, Ramacciotti E (2022) Rivaroxaban versus enoxaparin for thromboprophylaxis after major gynecological cancer surgery: the VALERIA trial: Venous thromboembolism prophylAxis after gynecoLogical pElvic cancer surgery with RIvaroxaban versus enoxAparin (VALERIA trial). Clin Appl Thromb Hemost. https://doi.org/10.1177/10760296221132556

    Article  PubMed  PubMed Central  Google Scholar 

  10. Kaatz S, Ahmad D, Spyropoulos AC, Schulman S (2015) Definition of clinically relevant non-major bleeding in studies of anticoagulants in atrial fibrillation and venous thromboembolic disease in non-surgical patients: communication from the SSC of the ISTH. J Thromb Haemost 13(11):2119–2126. https://doi.org/10.1111/jth.13140

    Article  CAS  PubMed  Google Scholar 

  11. Schulman S, Kearon C (2005) Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 3(4):692–694. https://doi.org/10.1111/j.1538-7836.2005.01204.x

    Article  CAS  PubMed  Google Scholar 

  12. Higgins JPT, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, Savovic J, Schulz KF, Weeks L, Sterne JAC (2011) The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ (Clinical Research ed.) 343:d5928. https://doi.org/10.1136/bmj.d5928

    Article  PubMed  Google Scholar 

  13. Wells GA, Shea B, O'Connell D, Peterson J, Welch V, Losos M, Tugwell P (2021) The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa Hospital Research Institute Research Programs

  14. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Controlled Clin Trials 7(3):177–188. https://doi.org/10.1016/0197-2456(86)90046-2

    Article  CAS  PubMed  Google Scholar 

  15. Higgins JPT, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ (Clinical Research ed.) 327(7414):557–560

    Article  PubMed  Google Scholar 

  16. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ (Clinical Research ed.) 315(7109):629–634

    Article  CAS  PubMed  Google Scholar 

  17. Guo Q, Huang B, Zhao J, Ma Y, Yuan D, Yang Y, Du X (2017) Perioperative pharmacological thromboprophylaxis in patients with cancer: a systematic review and meta-analysis. Ann Surg 265(6):1087–1093. https://doi.org/10.1097/sla.0000000000002074

    Article  PubMed  Google Scholar 

  18. Knoll W, Fergusson N, Ivankovic V, Wang TF, Caiano L, Auer R, Carrier M (2021) Extended thromboprophylaxis following major abdominal/pelvic cancer-related surgery: a systematic review and meta-analysis of the literature. Thromb Res 204:114–122. https://doi.org/10.1016/j.thromres.2021.06.010

    Article  CAS  PubMed  Google Scholar 

  19. Khorana AA, McCrae KR, Milentijevic D, Fortier J, Nelson WW, Laliberté F, Crivera C, Lefebvre P, Yannicelli D, Schein J (2017) Current practice patterns and patient persistence with anticoagulant treatments for cancer-associated thrombosis. Res Pract Thromb Haemost 1(1):14–22. https://doi.org/10.1002/rth2.12002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Li A, Garcia DA, Lyman GH, Carrier M (2019) Direct oral anticoagulant (DOAC) versus low-molecular-weight heparin (LMWH) for treatment of cancer associated thrombosis (CAT): a systematic review and meta-analysis. Thromb Res 173:158–163. https://doi.org/10.1016/j.thromres.2018.02.144

    Article  CAS  PubMed  Google Scholar 

  21. Seo S, Ryu MH, Kang YK, Kim KP, Chang HM, Ryoo BY, Kim SB, Lee JL, Park SR (2016) Oral rivaroxaban versus subcutaneous low molecular weight heparin treatment for venous thromboembolism in patients with upper gastrointestinal, hepatobiliary and pancreatic cancer. Ann Oncol 27:234. https://doi.org/10.1093/annonc/mdw371.87

    Article  Google Scholar 

  22. Haykal T, Zayed Y, Deliwala S, Kerbage J, Ponnapalli A, Malladi S, Goranta S, Samji V, Adam S (2020) Direct oral anticoagulant versus low-molecular-weight heparin for treatment of venous thromboembolism in cancer patients: an updated meta-analysis of randomized controlled trials. Thromb Res 194:57–65. https://doi.org/10.1016/j.thromres.2020.06.025

    Article  CAS  PubMed  Google Scholar 

  23. Giustozzi M, Agnelli G, Del Toro-Cervera J, Klok FA, Rosovsky RP, Martin AC, Herold J, Tzoran I, Szmit S, Bertoletti L, Becattini C, Huisman MV (2020) Direct oral anticoagulants for the treatment of acute venous thromboembolism associated with cancer: a systematic review and meta-analysis. Thromb Haemost 120(7):1128–1136. https://doi.org/10.1055/s-0040-1712098

    Article  PubMed  Google Scholar 

  24. Elbadawi A, Shnoda M, Mahmoud K, Elgendy IY (2021) Efficacy and safety of direct oral anticoagulants vs. low molecular weight heparin for cancer-related venous thromboembolism: a meta-analysis of randomized trials. Eur Heart J Cardiovasc Pharmacother 7(5):380–388. https://doi.org/10.1093/ehjcvp/pvaa067

    Article  PubMed  Google Scholar 

  25. Nagy A, Tegge AN, Borden LE, Osborne JL, Valea FA, Iglesias DA (2018) A retrospective comparison of oral rivaroxaban versus subcutaneous low-molecular-weight heparin for postoperative thromboprophylaxis in women with a gynecologic malignancy.  Gynecol Oncol 149:199–200. https://doi.org/10.1016/j.ygyno.2018.04.453

    Article  Google Scholar 

  26. Spénard E, Geerts W, Lin Y, Gien LT, Kupets R, Covens A, Vicus D (2023) Apixaban for extended postoperative thromboprophylaxis in gynecologic oncology patients undergoing laparotomy. Gynecol Oncol 172:9–14. https://doi.org/10.1016/j.ygyno.2023.02.012.

    Article  CAS  PubMed  Google Scholar 

  27. Swaroop M, Borden L, Locklear T, Armbruster S, Saks E, Osborne J, Valea F, Iglesias D (2021) Postoperative thromboprophylaxis with oral rivaroxaban versus subcutaneous low-molecular-weight heparin: a retrospective comparison in women with a gynecologic malignancy. Gynecol Oncol 162:S239. https://doi.org/10.1016/S0090-8258(21)01105-7

    Article  Google Scholar 

  28. Rashid MF, Jackson TL, Morgan JA, Dwyer FA, Schrope BA, Chabot JA, Kluger MD (2019) Dabigatran (pradaxa) is safe for extended venous thromboembolism prophylaxis after surgery for pancreatic cancer. J Gastrointest Surg 23(6):1166–1171. https://doi.org/10.1007/s11605-018-3936-1

    Article  PubMed  Google Scholar 

  29. Rich JM, Elkun Y, Geduldig J, Lavallee E, Mehrazin R, Attalla K, Wiklund P, Sfakianos JP (2023) Outcomes from a prospectively implemented protocol using apixaban after robot–assisted radical cystectomy. BJU Int 132(4):390–396. https://doi.org/10.1111/bju.16036

    Article  CAS  PubMed  Google Scholar 

  30. Westerman ME, Bree KK, Msaouel P, Kukreja JB, Mantaring C, Rukundo I, Gonzalez MG, Gregg JR, Casteel KN, Matin SF (2022) Apixaban vs enoxaparin for post-surgical extended-duration venous thromboembolic event prophylaxis: a prospective quality improvement study. J Urol 208(4):886–895. https://doi.org/10.1097/JU.0000000000002788

    Article  PubMed  Google Scholar 

  31. Ortiz RM, Golijanin B, O'Rourke TK, Sobel DW, Pillsbury L, Tucci CT, Caffery P, Golijanin D (2021) Direct oral anticoagulants for venous thromboembolism prophylaxis following robot-assisted radical cystectomy: a retrospective feasibility study at a single academic medical center. Urology 156:154–162. https://doi.org/10.1016/j.urology.2021.04.054

    Article  PubMed  Google Scholar 

Download references

Funding

Open access funding is provided by Fujian Maternity and Child Health Hospital. The authors received no funding for this work.

Author information

Author notes

  1. Hong Zhou and Ling-Ling Ye have contributed equally to this work and share first authorship.

Authors and Affiliations

  1. Department of Pharmacy, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, 350001, Fujian, China

    Hong Zhou, Ling-Ling Ye, Jin-Tuo Zhou, Fu-Xin Ma & Jin-Hua Zhang

  2. School of Medicine, Huaqiao University, Quanzhou, 362021, Fujian, China

    Jun-Jie Ma

Authors
  1. Hong Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ling-Ling Ye
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jin-Tuo Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fu-Xin Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jun-Jie Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jin-Hua Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

JHZ and HZ: conceived and designed the study. JHZ and JJM: supervised the study. HZ, LLY, JTZ, and FXM: reviewed the literature, collected, analyzed, and interpreted the data, and drafted the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Jun-Jie Ma or Jin-Hua Zhang.

Ethics declarations

Disclosures

Hong Zhou, Ling-Ling Ye, Jin-Tuo Zhou, Fu-Xin Ma, Jin-Jie Ma, and Jin-hua Zhang have no conflicts of interest or financial ties to disclose.

Ethical approval

This systematic review and meta-analysis does not require ethical approval.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 337 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhou, H., Ye, LL., Zhou, JT. et al. Direct oral anticoagulants (DOACs) versus low-molecular-weight heparin (LMWH) for extended thromboprophylaxis following major abdominal/pelvic cancer-related surgery: a systematic review and meta-analysis. Surg Endosc 38, 1131–1138 (2024). https://doi.org/10.1007/s00464-023-10649-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00464-023-10649-y

Keywords

Search

Navigation