The Comparison of Novel Oral Anticoagulants with Conventional Anticoagulants in the Treatment of Cancer-Associated Thrombosis: A Systemic Review

Introduction: Venous thromboembolism (VTE) is one of the major causes of mortality among patients with malignancy. It is estimated that around 4-20% of patients with cancer experience venous thrombosis. Typically, low molecular weight heparin (LMWH) is used as an initial agent of choice in VTE except in patients with renal insufficiency who cannot tolerate LMWH and require alternate therapy. Also, despite adequate therapy, VTE recurrence is common among cancer patients. The novel oral anticoagulants (NOACs) have recently been introduced in the treatment of VTE and have shown promising results. We have performed a systemic review of the literature comparing the safety and efficacy profiles of NOACs with LWMH in cancer patients with VTE. Methods: We performed a comprehensive literature search completed on July 7, 2020, on Pubmed, Cochrane library, and ClinicalTrials.gov. We used the MeSH terms: ‘venous thrombosis’, ‘neoplasms’, ‘rivaroxaban’, ‘dabigatran’, and ‘enoxaparin’ with associated entry terms. Our search yielded 46 studies. Following PRISMA guidelines and subsequent screening by three reviewers, we shortlisted 5 completed clinical trials (n=2873) and included data from these studies in our systemic review. Results: EINSTEIN-PE investigators (2013, n=223) reported a net clinical benefit (VTE plus major bleeding) in 83 patients (3.4%) vs 96 patients (4%) in the rivaroxaban arm versus control arm (enoxaparin + warfarin/acenocoumarol arm) respectively (HR 0.85 [95% CI 0.63-1.14], p=0.28). Recurrence occurred in 2.1% vs 1.8% (HR 1.12 [95% CI 0.75-1.68] p=0.003). Major bleed events occurred in 1.1% vs 2.2% (HR 0.49 [95% CI 0.31-0.79] p=0.003). Clinically relevant minor bleed events occurred in 9.5% vs 9.8%. Deaths were lower in rivaroxaban arm (20 vs 23). Hokusai-VTE investigators (2013, n=414) reported edoxaban as non-inferior to warfarin when compared the primary efficacy (defined as recurrence of symptomatic VTE) 3.2% vs 3.5% respectively (HR 0.89 [95% CI 0.70 to 1.13] p