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Meta-Analysis
. 2019 Jan:173:158-163.
doi: 10.1016/j.thromres.2018.02.144. Epub 2018 Mar 2.

Direct oral anticoagulant (DOAC) versus low-molecular-weight heparin (LMWH) for treatment of cancer associated thrombosis (CAT): A systematic review and meta-analysis

Ang Li  1 , David A Garcia  2 , Gary H Lyman  3 , Marc Carrier  4
Affiliations
Meta-Analysis

Direct oral anticoagulant (DOAC) versus low-molecular-weight heparin (LMWH) for treatment of cancer associated thrombosis (CAT): A systematic review and meta-analysis

Ang Li et al. Thromb Res. 2019 Jan.

Abstract

Introduction: It is unclear if direct oral anticoagulants (DOACs) are effective and safe alternatives to low-molecular-weight heparin (LMWHs) for the treatment of cancer-associated venous thromboembolism (VTE). We aim to synthesize existing literature that compared DOACs versus LMWHs in this high-risk population.

Materials and methods: We conducted a systematic review using EMBASE, MEDLINE and CENTRAL for all observational studies and randomized controlled trials (RCTs) (PROSPERO: CRD42017080898). Two authors independently reviewed study eligibility, extracted data, and assessed bias. Primary outcomes included 6-month recurrent VTE and major bleeding. Secondary outcomes included clinically relevant non-major bleeding (CRNMB) and mortality.

Results: We screened 426 articles, reviewed 25 in full-text, and selected 13 and 2 for qualitative and quantitative synthesis, respectively. Based on a meta-analysis of the 2 RCTs, DOACs had lower 6-month recurrent VTE (42/725) when compared to LMWH (64/727) (RR: 0.65 (0.42-1.01)). However, DOACs had higher major bleeding (40/725) when compared to LMWH (23/727) (RR 1.74 (1.05-2.88)). Similarly, CRNMB was higher (RR 2.31 (0.85-6.28)) for patients receiving DOACs. There was no difference in mortality (RR 1.03 (0.85-1.26)). Observational studies were heterogeneous with high risks of bias but showed recurrent VTE rates consistent with the meta-analysis.

Conclusions: DOACs were more effective than LMWHs to prevent recurrent VTE but were associated with a significantly increased risk of major bleeding as well as a trend toward more CRNMB. The absolute risk differences were small (2-3%) for both primary outcomes and may reflect better compliance with DOACs than LMWHs.

Keywords: Factor Xa inhibitors; Heparin; Low-molecular-weight; Neoplasms; Venous thrombosis.

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Conflict of interest statement

Declarations of Interest: none

Figures

Figure 1
Figure 1
PRISMA flow diagram for study inclusion and exclusion.
Figure 2
Figure 2
Forest plots of relative risks (RRs) for pooled outcome comparisons between DOAC and LMWH from randomized controlled trials. (A) VTE recurrence by 6-month, (B) major bleeding by 6-month, (C) clinically relevant non-major bleeding (CRNMB) by 6-month, (D) overall mortality by 6-month. Gray boxes superimposing RR estimates are proportional to the weight of the included study. Heterogeneity between trials were assessed by the I2 statistic.
Figure 3
Figure 3
Risk of bias summary. Cochrane Risk of Bias Tool for randomized controlled trials is used to assess bias for the randomized trials (Raskob 2017 and Young 2017). ROBINS-I is used to assess bias for the observational studies. + low risk, − high risk, ? unclear/insufficient information.
See this image and copyright information in PMC

Comment in

References

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