An update on the efficacy and safety of novel anticoagulants for cancer associated thrombosis

ABSTRACT

Introduction: Cancer-associated thrombosis (CAT) refers to the most common thromboembolic complication of cancer which is venous thromboembolism (VTE). CAT primary prophylaxis, treatment, and secondary prevention are challenging for the complexity of cancer patients, who exhibit hypercoagulability with concomitant-heightened bleeding risk.

Areas covered: In this review, the author examines the role of low molecular weight heparins (LMWH), which have been the standard of care for CAT treatment for many years. Direct oral anticoagulants (DOACS) have practical advantages over subcutaneous LMWH, especially for long-term therapy. The author then discusses the results of two RCTs which separately compared the direct oral factor Xa inhibitors, apixaban or rivaroxaban, with placebo for CAT prophylaxis in ambulatory high-risk cancer patients and found that DOACS reduced VTE but increased bleeding. Finally, the author discusses four RCTS separately comparing an oral direct factor Xa inhibitor (edoxaban, rivaroxaban, or apixaban) with LMWH for CAT treatment. DOACS showed non-inferior efficacy, although rivaroxaban and edoxaban showed higher bleeding rates, especially in gastrointestinal cancers.

Expert opinion: DOACS have a convenient route of administration and do not require laboratory monitoring, although choice of anticoagulants for CAT depends on factors such as tumor type, bleeding risk, concomitant drugs, and comorbidities.

KEYWORDS:

• Cancer associated thrombosis
• deep vein thrombosis
• pulmonary embolism
• venous thromboembolism
• direct oral anticoagulants
• direct Factor Xa inhibitors
• low molecular weight heparin
• vitamin K antagonists

Article highlights

1. Cancer patients are at high risk of thrombotic complications and cancer-associated thrombosis (CAT) refers to the most common of such complications which is venous thromboembolism.

2. CAT prophylaxis and treatment are problematic in cancer patients because they also exhibit a high risk of bleeding.

3. LMWH have been the recommended standard of care for CAT treatment for their similar, or superior, efficacy when compared to vitamin K antagonists in RCTS.

4. Direct oral anticoagulants (DOACS) are advantageous over subcutaneous LMWH especially long–term.

5. DOACS, in particular oral direct factor Xa inhibitors (edoxaban, rivaroxaban, or apixaban) showed non-inferior efficacy when compared to LMWH in RCTS, although rivaroxaban and edoxaban showed higher bleeding rates, especially in gastrointestinal cancers.

6. The choice of anticoagulants in CAT depends on tumor type, bleeding risk, concomitant drugs and comorbidities and DOACS are an advantageous option for CAT.

This box summarizes key points contained in the article.

Declaration of interest

B Cosmi has served on speaker’s bureaus for Daiichi Sankyo, Sanofi, Instrumentation Laboratory Company, Janssen Pharmaceuticals and Werfen in the past 5 years. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript has not been funded.