Direct oral anticoagulants in cancer-associated thrombosis: A systematic review of cost-effectiveness studies

Cancer-associated thrombosis (CAT) is common in cancer patients and leads to higher morbidity, mortality, and healthcare costs. This systematic review assessed cost-effectiveness analyses (CEAs) that compared direct oral anticoagulants (DOACs) with low-molecular-weight heparin (LMWH) for CAT treatment, or with no prophylaxis for primary prevention in high-risk patients. This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, was registered with the International Prospective Register of Systematic Reviews (PROSPERO), and included searches of databases from January 2008 to December 2024 for full economic evaluations comparing DOACs with LMWH or no prophylaxis for the prevention or treatment of CAT. Study quality was assessed using the Drummond checklist for methodological rigour and the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist for reporting quality. Fourteen studies met the inclusion criteria: nine focused on treatment, and five on prevention. Most analyses adopted a healthcare perspective. Overall, DOACs showed favourable cost-effectiveness for CAT treatment and prophylaxis. From the healthcare perspective, DOACs were more cost-effective than LMWH, often associated with lower costs and higher Quality-Adjusted Life-Years (QALYs), with negative incremental cost-effectiveness ratios (ICERs) indicating dominance. Apixaban consistently demonstrated strong cost-effectiveness, whereas rivaroxaban and edoxaban yielded mixed results, depending on the setting and patient subgroup. For prophylaxis, DOACs generally provide better value than LMWH or no prophylaxis, particularly over longer time horizons, with apixaban and rivaroxaban being the most favourable. Despite variability among different perspectives, the evidence supports the use of DOACs, particularly apixaban, as cost-effective options for CAT management. Rivaroxaban also demonstrated consistently favourable outcomes, while edoxaban showed mixed results but was cost-effective from a societal perspective. • CAT presentation varies from minor clots to severe, life-threatening events. • LMWH needs injections; DOACs are oral but raise bleeding and cost concerns. • Most studies show DOACs outperform LMWH, often cheaper with higher QALYs.