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Li A, Kuderer NM, Garcia DA, et al. Direct oral anticoagulant for the prevention of thrombosis in ambulatory patients with cancer: A systematic review and meta-analysis. J Thromb Haemost. 2019 Aug 17. doi: 10.1111/jth.14613. (Systematic review)
Abstract

BACKGROUND: It is unclear if direct oral anticoagulant (DOAC) is efficacious and safe for prophylaxis of venous thromboembolism (VTE) in ambulatory patients with cancer.

METHODS: We performed a systematic review using EMBASE, MEDLINE, and CENTRAL. Inclusion criteria included adult ambulatory patients with cancer, prophylactic use of DOAC, and randomized controlled trials. Exclusion criteria included pediatric patients, inpatient or postoperative setting, therapeutic indication of DOAC, or non-phase III randomized controlled trial. Two authors screened/reviewed articles and abstracted the data. Meta-analysis was performed using random-effects model. Efficacy outcome included overall and symptomatic VTE incidence during the first 6 months. Safety outcomes included major bleeding and clinically relevant non-major bleeding (CRNMB) incidence during the on-treatment period. Subgroup analysis was performed for intermediate- and high-risk Khorana score.

RESULTS: A total of 202 records were identified and 28 full-text articles were assessed. Two studies with 1415 participants were included for meta-analysis. For DOAC vs placebo, the relative risks for overall and symptomatic VTE incidence by 6 months were 0.56 (0.35-0.89) and 0.58 (0.29-1.13), respectively. The relative risks for major bleeding and CRNMB while on-treatment were 1.96 (0.80-4.82) and 1.28 (0.74-2.20), respectively. Patients with high-risk Khorana score (3+) derived the largest absolute risk reduction of VTE.

CONCLUSIONS: Low-dose DOAC reduces the rate of overall VTE in higher risk cancer patients starting systemic chemotherapy. It may reduce the rate of symptomatic VTE but increase the likelihood of bleeding.

Ratings
Discipline Area Score
Physician 6 / 7
Comments from MORE raters

Physician rater

Meta-analysis of only 2 trials that are dissimilar to the extent that it raises the question about whether the data should be combined. The article is valuable as a summary of two related studies. Despite the design differences, the studies had similar findings, which suggest that prophylactic dose DOAC may decrease VTE and increase bleeding for patients with cancer.

Physician rater

Venous thromboembolism is a significant cause of morbidity and mortality in ambulatory cancer patients. Use of a direct oral anticoagulants in patients at high risk reduces the rate of VTE, but comes with an increased rate of bleeding. Patients with a Khorana score of 3 or higher have the greatest benefit from DOAC VTE prophylaxis in the ambulatory setting.
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