A literature review of venous thromboembolism prophylaxis in cancer patients using direct oral anticoagulation

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Shawarsky, Mark
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Introduction: Venous thromboembolism (VTE) risk is four to seven times greater in cancer patients than the general population and is the leading cause of morbidity and mortality among such patients receiving chemotherapy. Direct oral anticoagulants (DOACs) have become a standard of care along with low molecular weight heparins (LMWHs) for the treatment of VTE in non-cancer patients. Recent studies have investigated prophylactic DOAC use for cancer patients and have provided the first evidence of benefit for certain high-risk patients. Objective: This literature review reviewed available evidence to determine whether DOACs are acceptable alternatives to LMWHs for VTE prophylaxis in cancer patients and if certain patient characteristics would preclude their use in this population. Methods: This review searched the PUBMED and MEDLINE databases for papers of relevance published in the past decade that addressed the research question using search terms related to DOACs, VTE, cancer and prophylaxis. Three phase 3 clinical trials were identified using this approach and a further phase 2 clinical trials was found via manual reference list review of the yielded results. Results: The two phase 3 trials conducted in ambulatory cancer patients comparing the DOACs apixaban and rivaroxaban to placebo demonstrated modest to limited benefit of DOAC use for prophylaxis in intermediate to high-risk patients based on previously validated risk assessment scores. Major bleeding events were primarily clustered in those with gastrointestinal (GI) and gynaecological malignancies, though overall events were in keeping with LMWH trials conducted previously. The third phase 3 trial comparing a DOAC to a LMWH was unhelpful in answering our clinical question as, among the numerous issues uncovered with the trial, it included patients with a past cancer history, rather than active cancer, as the majority of the cancer subgroup. Conclusion: When utilizing a validated risk assessment score in cancer patients, the DOACs apixaban and rivaroxaban appear to be equally valid options to LMWHs for VTE prophylaxis in cancer patients. The precise context and clinical role of this intervention would best be clarified by dedicated phase 3 trials comparing LMWHs to DOACs in intermediate to high-risk cancer patients. No patient characteristics have shown to be conclusively at a higher risk of major bleeding, but future trials should consider
venous thromboembolism prophylaxis, cancer patients, direct oral anticoagulation