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Li A, Garcia DA, Lyman GH, et al. Direct oral anticoagulant (DOAC) versus low-molecular-weight heparin (LMWH) for treatment of cancer associated thrombosis (CAT): A systematic review and meta-analysis. Thromb Res. 2018 Mar 2. pii: S0049-3848(18)30216-0. doi: 10.1016/j.thromres.2018.02.144.
Area Score
Hematology
Oncology - General
Internal Medicine
Hemostasis and Thrombosis
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.

Comments from MORE raters

Hemostasis and Thrombosis rater

There are only 2 RCTs but their results are generally consistent with each other. The observational trials lend further support for the main conclusions.

Hemostasis and Thrombosis rater

This won`t be news to physicians who are familiar with the 2 RCTs.

Internal Medicine rater

This would certainly be an easier option than LMWH.

Internal Medicine rater

This issue comes up, not frequently but often enough to be encountered several times each year, in a primary care practice. It would certainly be nice to have something other than injectable LMWH for these patients. So, the topic is of interest. I`d have a hard look at the paper, though. I normally don`t consider a meta-analysis of 2 studies to be justified, as opposed to a narrative review of the two studies. Figures like their Figure 2 are not worthy of appearing in a publication, in my view. And the authors` statement that they used a random effects model, using the D-L estimator, to construct these pooled analyses is either naïve or disingenuous. This makes me wonder about their methodologic skills, which in turn can manifest itself in all kinds of ways that would be undetectable to readers and reviewers. This paper would not have gotten past the peer-review stage in my editorial hands.

Oncology - General rater

The use of DOAC's has been controversial in the oncology population. This study provides data that will assist physicians and patients in making decision on which type of agent to use. \In the compliant patient, I would still use LMWH's as my first choice due to lower risk of bleeding and quicker reversibility of anticoagulation compared to DOAC's. Depending on risk, DOAC's could be used cautiously in less compliant patients.