Chest
Volume 147, Issue 2, February 2015, Pages 475-483
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Original Research: Pulmonary Vascular Disease
Direct Oral Anticoagulants in Patients With VTE and Cancer

https://doi.org/10.1378/chest.14-0402Get rights and content

BACKGROUND

Direct oral anticoagulants (DOAs) have been shown to be as effective and at least as safe as conventional anticoagulation for the prevention of recurrences in patients with VTE. Whether this is the case in patients with cancer-associated VTE remains undefined.

METHODS

We performed a meta-analysis of randomized controlled trials with the aim of assessing the efficacy and safety of DOAs in patients with VTE and cancer. MEDLINE, EMBASE, and CENTRAL were searched up to December 2013 with no language restriction. The primary outcome of the analysis was recurrent VTE. Data on major bleeding (MB) and clinically relevant nonmajor bleeding were analyzed. Data were pooled and compared by ORs and 95% CIs.

RESULTS

Overall, 10 studies comparing DOAs with conventional anticoagulation for treatment of VTE including patients with cancer were included in the review. Six studies were included in the meta-analysis (two with dabigatran, two with rivaroxaban, one with edoxaban, and one with apixaban), accounting for a total of 1, 132 patients. VTE recurred in 23 of 595 (3.9%) and in 32 of 537 (6.0%) patients with cancer treated with DOAs and conventional treatment, respectively (OR, 0.63; 95% CI, 0.37-1.10; I2, 0%). MB occurred in 3.2% and 4.2% of patients receiving DOAs and conventional treatment, respectively (OR, 0.77; 95% CI, 0.41-1.44; I2, 0%).

CONCLUSIONS

DOAs seem to be as effective and safe as conventional treatment for the prevention of VTE in patients with cancer. Further clinical trials in patients with cancer-associated VTE should be performed to confirm these results.

Section snippets

Data Sources and Searches

A protocol for this review was prospectively developed detailing the specific objectives; criteria for study selection; approach to assess study quality, outcomes, and statistical methods. We performed an unrestricted search in MEDLINE, EMBASE, and CENTRAL through December 17, 2013. The search strategy is reported in e-Table 1. No language restrictions were applied. Reference lists of retrieved articles and review articles were manually searched for other relevant studies. The term ximelagatran

Results

Overall, 915 studies were found, and 26 were selected as potentially relevant. The flow diagram for study selection is reported in Figure 1. Ten studies that reported data on patients with cancer were included in the systematic review. Interobserver agreement for study selection was good (κ = 0.87).

Baseline characteristics of the studies included in the systematic review are reported in Table 1. All trials were randomized. Reports on three phase 2 trials were selected (one on apixaban28 and two

Discussion

This study shows that the efficacy and safety profile of new anti-Xa and anti-IIa drugs for VTE treatment in patients with cancer is similar to that observed in patients without cancer. A favorable trend toward reduction of recurrent VTE was observed without concern in terms of clinically relevant bleedings.

We found a nonsignificant reduction of recurrent VTE of about 40% in favor of DOAs compared with conventional treatment with heparin followed by vitamin K antagonists. The reduction was

Conclusions

New anti-Xa and anti-IIa drugs seem to be at least as effective and safe as conventional anticoagulant treatment with vitamin K antagonists for prevention of VTE recurrence in cancer patients. Ad hoc clinical trials should be conducted to confirm our results.

Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Agnelli reports receiving personal fees from Boehringer Ingelheim GmbH, Sanofi SA, Daiichi-Sankyo Co Ltd, Bristol-Myers Squibb,

Acknowledgments

Author contributions: M. C. V. served as principal author, had full access to all of the data in the study, and takes responsibility for the integrity of the data and the accuracy of the data analysis. M. C. V., F. G., and C. B. contributed to the study concept and design and data analysis; M. C. V., F. G., G. A., and C. B. contributed to data acquisition and interpretation; M. C. V. and F. G. contributed to drafting of the manuscript; and G. A. and C. B. contributed to revision of the

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    FUNDING/SUPPORT: The authors have reported to CHEST that no financial support was received for this study. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.

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