Are Direct Oral Anticoagulants (DOACs) better than Low Molecular Weight Heparin (LMWH) for recurring Venous Thromboembolism (VTE) in patients with cancer?

DOACs vs LMWH for Recurring VTE in Cancer Patients

DOACs are more effective than LMWH in preventing recurrent VTE in cancer patients, but with a higher risk of bleeding, particularly in those with gastrointestinal malignancies. 1, 2

Efficacy Comparison

• DOACs significantly reduce recurrent VTE compared to LMWH (5.2% vs 8.2%; RR 0.62,95% CI 0.43-0.91) in cancer patients, demonstrating superior efficacy in preventing thrombotic events 2
• The CANVAS trial showed DOACs were non-inferior to LMWH for preventing recurrent VTE with a difference of -2.7% (1-sided 95% CI, -100% to 0.7%), meeting the prespecified non-inferiority criterion 1
• Meta-analyses consistently demonstrate that DOACs are associated with lower rates of VTE recurrence compared to LMWH in cancer patients 3

Safety Considerations

• DOACs are associated with a higher risk of clinically relevant non-major bleeding (10.4% vs 6.4%; RR 1.65,95% CI 1.19-2.28) compared to LMWH 2
• Major bleeding risk is particularly elevated in patients with gastrointestinal cancer treated with DOACs (RR 2.30,95% CI 1.08-4.88) 2
• The National Comprehensive Cancer Network recommends avoiding DOACs in patients with gastrointestinal and genitourinary malignancies, especially those with intact intraluminal tumors, due to significantly increased bleeding risk 4

Patient Selection Algorithm

Prefer DOACs over LMWH for:

• Most cancer patients without specific contraindications 5, 1
• Patients who prefer oral administration over subcutaneous injections 6
• Patients with good renal function (CrCl >15 mL/min) 7

Prefer LMWH over DOACs for:

• Patients with gastrointestinal malignancies (13.2% bleeding rate with edoxaban vs 2.4% with dalteparin) 4
• Patients with genitourinary malignancies, particularly those with unoperated or residual tumors 4
• Patients with central nervous system malignancies or recent CNS bleeding 4
• Patients with severe thrombocytopenia (<50,000/mL) 4
• Patients with severe renal dysfunction (CrCl <15 mL/min) 7
• Patients taking medications with significant drug-drug interactions with DOACs 6

Specific DOAC Considerations

• Apixaban may be preferred over other DOACs in patients with higher bleeding risk but without absolute contraindications to DOACs 7
• Edoxaban may be preferred in some cancer patients as it has fewer drug interactions with chemotherapy agents 5
• All DOACs should be avoided in patients with severe renal impairment (CrCl <15 mL/min) and severe hepatic impairment 7

Common Pitfalls and Caveats

• Failure to recognize that cancer type significantly impacts bleeding risk with DOACs - gastrointestinal and genitourinary cancers have particularly high bleeding risk 4
• Overlooking potential drug-drug interactions between DOACs and anticancer agents, especially with tyrosine kinase inhibitors and immune-modulating agents 6
• Not accounting for chemotherapy-induced nausea and vomiting which may affect DOAC absorption 6
• Neglecting to reassess anticoagulation strategy if cancer status changes during treatment 4

Duration of Therapy

• For cancer-associated thrombosis, treatment should continue as long as the patient has active malignancy and therapy is not otherwise contraindicated 5
• Regular reassessment of bleeding risk and efficacy is essential throughout the treatment course 4