Non-Vitamin K Antagonist Oral Anticoagulants versus Low Molecular Weight Heparin for Cancer-Related Venous Thromboembolic Events: Individual Patient Data Meta-Analysis

Chun En Yau; Chen Ee Low; Natasha Yixuan Ong; Sounak Rana; Lucas Jun Rong Chew; Sara Moiz Tyebally; Ping Chai; Tiong-Cheng Yeo; Mark Y Chan; Matilda Xinwei Lee; Li-Ling Tan; Chieh-Yang Koo; Ainsley Ryan Yan Bin Lee; Ching-Hui Sia

doi:10.3390/cancers15245887

Non-Vitamin K Antagonist Oral Anticoagulants versus Low Molecular Weight Heparin for Cancer-Related Venous Thromboembolic Events: Individual Patient Data Meta-Analysis

Cancers (Basel). 2023 Dec 18;15(24):5887. doi: 10.3390/cancers15245887.

Authors

Chun En Yau¹, Chen Ee Low¹, Natasha Yixuan Ong¹, Sounak Rana¹, Lucas Jun Rong Chew¹, Sara Moiz Tyebally², Ping Chai^{1

3}, Tiong-Cheng Yeo^{1

3}, Mark Y Chan^{1

3}, Matilda Xinwei Lee⁴, Li-Ling Tan³, Chieh-Yang Koo³, Ainsley Ryan Yan Bin Lee¹, Ching-Hui Sia^{1

3}

Affiliations

¹ Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore.
² Division of Cardiology, Department of Medicine, Ng Teng Fong General Hospital, Singapore 609606, Singapore.
³ Department of Cardiology, National University Heart Centre, Singapore 119074, Singapore.
⁴ Department of Haematology-Oncology, National University Cancer Institute, Singapore 119228, Singapore.

Abstract

Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in cancer patients. Low molecular weight heparin (LMWH) has been the standard of care but new guidelines have approved the use of non-vitamin K antagonist oral anticoagulants (NOAC). By conducting an individual patient data (IPD) meta-analysis of randomised controlled trials (RCTs) comparing the outcomes of NOAC versus LMWH in cancer patients, we aim to determine an ideal strategy for the prophylaxis of VTE and prevention of VTE recurrence. Three databases were searched from inception until 19 October 2022. IPD was reconstructed from Kaplan-Meier curves. Shared frailty, stratified Cox and Royston-Parmar models were fit to compare the outcomes of venous thromboembolism recurrence and major bleeding. For studies without Kaplan-Meier curves, aggregate data meta-analysis was conducted using random-effects models. Eleven RCTs involving 4844 patients were included. Aggregate data meta-analysis showed that administering NOACs led to a significantly lower risk of recurrent VTE (RR = 0.65; 95%CI: 0.50-0.84) and deep vein thrombosis (DVT) (RR = 0.60; 95%CI: 0.40-0.90). In the IPD meta-analysis, NOAC when compared with LMWH has an HR of 0.65 (95%CI: 0.49-0.86) for VTE recurrence. Stratified Cox and Royston-Parmar models demonstrated similar results. In reducing risks of recurrent VTE and DVT among cancer patients, NOACs are superior to LMWHs without increased major bleeding.

Keywords: LMWH; Meta-analysis; NOAC; anticoagulation.

Publication types

Review

Grants and funding

ARYBL is supported by the National University of Singapore Yong Loo Lin School of Medicine Dean’s Research Development Award. CHS was supported by the National University of Singapore Yong Loo Lin School of Medicine’s Junior Academic Fellowship Scheme, as well as the Singapore Ministry of Health National Medical Research Council’s Transition Award (MOH-001368-00).