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Review
. 2023 Dec 18;15(24):5887.
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

Chun En Yau  1 , Chen Ee Low  1 , Natasha Yixuan Ong  1 , Sounak Rana  1 , Lucas Jun Rong Chew  1 , Sara Moiz Tyebally  2 , Ping Chai  1   3 , Tiong-Cheng Yeo  1   3 , Mark Y Chan  1   3 , Matilda Xinwei Lee  4 , Li-Ling Tan  3 , Chieh-Yang Koo  3 , Ainsley Ryan Yan Bin Lee  1 , Ching-Hui Sia  1   3
Affiliations
Review

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 et al. Cancers (Basel). .

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.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flowchart.
Figure 2
Figure 2
Forest plot of recurrent venous thromboembolism outcomes [7,15,16,23,24,35,37]. Vertical reference line indicates a risk ratio of 1. Diamond represents the aggregated effect size.
Figure 3
Figure 3
Forest plot of recurrent deep vein thrombosis outcomes [7,15,23,36,37]. Vertical reference line indicates a risk ratio of 1. Diamond represents the aggregated effect size.
Figure 4
Figure 4
Forest plot of major bleeding outcomes [7,15,16,23,24,33,34,35,36,37]. Vertical reference line indicates a risk ratio of 1. Diamond represents the aggregated effect size.
Figure 5
Figure 5
Cumulative incidence curve of pooled cohorts for recurrent venous thromboembolism.
Figure 6
Figure 6
Cumulative incidence curve of pooled cohorts for major bleeding.
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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).

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