Direct oral anticoagulants vs low-molecular-weight heparins for cancer-associated thromboembolism

doi:10.12998/wjcc.v14.i17.118087

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World Journal of Clinical Cases

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2307-8960

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Clin Cases. Jun 16, 2026; 14(17): 118087
Published online Jun 16, 2026. doi: 10.12998/wjcc.v14.i17.118087

Direct oral anticoagulants vs low-molecular-weight heparins for cancer-associated thromboembolism

Faseeh Haider, Faizan Ahmed, Yusra Junaid, Maliha Khalid, Areej Dar, Muhammad Arham, Aman Ullah, Saba Aliha, Muhammad Usman Arshad, Khadija Naeem, Muhammad Moseeb Ali Hashim, Najam Gohar, Asha Ricciuti, Vipul Bhanderi, Fawaz Alenezi, Brijesh Patel

Faseeh Haider, Department of Internal Medicine, Allama Iqbal Medical College, Lahore 54550, Punjab, Pakistan

Faizan Ahmed, Department of Internal Medicine, Jersey Shore University Medical Center, Neptune, NJ 07753, United States

Yusra Junaid, Department of Internal Medicine, Dow Medical College, Karachi 74200, Sindh, Pakistan

Maliha Khalid, Department of Medicine, Jinnah Sindh Medical University, Karachi 75510, Sindh, Pakistan

Areej Dar, Department of Medicine, Shaikh khalifa bin Zayed Al Nahyan Medical College, Lahore 54600, Punjab, Pakistan

Muhammad Arham, Department of Medicine, Sheikh Zayed Medical College, Rahimyar Khan 64200, Punjab, Pakistan

Aman Ullah, Department of Internal Medicine, University of Missouri-Columbia, Columbia, MO 65211, United States

Saba Aliha, Department of Medicine, Multan Medical and Dental College, Multan 06006, Punjab, Pakistan

Muhammad Usman Arshad, Department of Medicine, Shalamar Medical and Dental College, Lahore 54840, Punjab, Pakistan

Khadija Naeem, Department of Medicine, Montefiore St.Luke’s Cornwall, New York, NY 12518, United States

Muhammad Moseeb Ali Hashim, Department of Pathology, University of Missouri-Columbia, Columbia, MO 65211, United States

Najam Gohar, Department of Internal Medicine, Ameer-ud-Din Medical College, Postgraduate Medical Institute, Lahore 54000, Punjab, Pakistan

Asha Ricciuti, Department of Medicine, SSM Health St Louis University Hospital, St. Louis, MO 63104, United States

Vipul Bhanderi, Department of Medicine, University of Missouri-Columbia, Columbia, MO 65211, United States

Fawaz Alenezi, Department of Medicine, Duke University School of Medicine, Durham, NC 27710, United States

Brijesh Patel, Department of Cardiology, Indiana University School of Medicine, Indianapolis, IN 46202, United States

Author contributions: Haider F designed the research study; Haider F and Junaid Y led the project; Khalid M, Dar A, Aliha S, Naeem K, Ali M, Arham M and Arshad U screened the articles and extracted the data; Khalid M, Dar A, Aliha S and Naeem K wrote the manuscript; Hashim MMA, Arham M, Ullah A, Gohar N analyzed the data; Ahmed F, Ricciuti A, Bhanderi V, Alenezi F, Patel B reviewed the manuscript. All authors have read and approved the final manuscript.

AI contribution statement: We did use AI tools solely for paraphrasing certain sentences to improve clarity and readability. All content, data analysis, study design, results, and interpretations are original, based on our own research and writing. No AI was involved in generating ideas, methods, or conclusions. We are happy to provide further details or revised sections if needed.

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.

Corresponding author: Faseeh Haider, Researcher, Department of Internal Medicine, Allama Iqbal Medical College, Allama Shabbir Ahmed Usmani Road, Lahore 54550, Punjab, Pakistan. faseehhaidermd@gmail.com

Received: December 23, 2025
Revised: March 11, 2026
Accepted: May 12, 2026
Published online: June 16, 2026
Processing time: 162 Days and 13.1 Hours

Abstract

BACKGROUND

Direct oral anticoagulants (DOACs) have demonstrated great potential in preventing recurrent cancer-related thromboembolism and offer an alternative to low-molecular-weight heparins (LMWHs) in active cancer patients.

AIM

To compare DOACs versus LMWH for venous thromboembolism (VTE), mortality, and bleeding risks in cancer-associated thrombosis, and identify outcome moderators.

METHODS

Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, we retrieved relevant literature from MEDLINE, the Cochrane Library, EMBASE, ScienceDirect, and Scopus up to April 2025. We performed subgroup analyses by anticoagulation regimen and study design. Meta-regression was used to assess the impact of the clinical variables age, body mass index, sex, metastasis, thrombocytopenia, and creatinine levels (> 60 μmol/L vs < 60 μmol/L). The study analysis was performed using the (rma) R (v2025.05.0+49) meta package via Restricted Maximum Likelihood estimation.

RESULTS

Twenty-nine studies (n = 42379) were analyzed. DOACs lowered VTE risk vs LMWHs [risk ratio (RR) = 0.76; 95% confidence interval (CI): 0.64-0.90; I² = 41.9%], with the greatest reduction with apixaban (RR = 0.55; 95%CI: 0.40-0.76; I² = 3.4%; P = 0.008). Deep vein thrombosis decreased (RR = 0.61; 95%CI: 0.42-0.89; P = 0.02; I² = 0%). Clinically relevant non-major bleeding increased with rivaroxaban (RR = 1.66; 95%CI: 1.19-2.30; P = 0.04). Metastasis predicted major bleeding (β = 1.91; P = 0.008) and mortality (β = 0.668; P = 0.026); female sex predicted minor bleeding (β = 3.13; P = 0.04). Excluding McBane et al, mortality decreased (RR = 0.73; 95%CI: 0.55-0.97; I² = 94.4%).

CONCLUSION

DOACs, especially apixaban, are associated with reduced risk of VTE and mortality vs LMWHs. Overall, bleeding was similar; rivaroxaban increased clinically relevant non-major bleeding. Female sex, metastasis, and thrombocytopenia affected bleeding and mortality.

Keywords: Cancer-associated thrombosis; Direct oral anticoagulants; Low molecular weight heparins; Meta-regression; Factor Xa inhibitors; Neoplasms

Core Tip: Cancer-associated thrombosis continues to be a major cause of morbidity and mortality in oncology patients, necessitating the selection of anticoagulation medication. This study examined the efficacy and safety of direct oral anticoagulants vs low-molecular-weight heparins. Direct oral anticoagulants showed comparable protection against venous thromboembolism and severe bleeding, with apixaban demonstrating a significant reduction in venous thromboembolism recurrence. Metastasis and platelet count were found as major moderators of bleeding and mortality outcomes in study, indicating the need for personalized anticoagulation methods in cancer treatment.