Cost–utility analysis of apixaban compared with usual care for primary thromboprophylaxis in ambulatory patients with cancer

Background:Apixaban (2.5 mg) taken twice daily has been shown to substantially reduce the risk of venous thromboembolism (VTE) compared with placebo for the primary thromboprophylaxis of ambulatory patients with cancer who are starting chemotherapy and are at intermediate-to-high risk of VTE. We aimed to compare the health system costs and health benefits associated with primary thromboprophylaxis using apixaban with those associated with the current standard of care (where no primary thromboprophylaxis is given), from the perspective of Canada’s publicly funded health care system in this subpopulation of patients with cancer over a lifetime horizon.Methods:We performed a cost–utility analysis to estimate the incremental cost per quality-adjusted life-year (QALY) gained with primary thromboprophylaxis using apixaban. We obtained baseline event rates and the efficacy of apixaban from the Apixaban for the Prevention of Venous Thromboembolism in High-Risk Ambulatory Cancer Patients (AVERT) trial on apixaban prophylaxis. We estimated relative risk for bleeding, risk of complications associated with VTE treatment, mortality rates, costs and utilities from other published sources.Results:Over a lifetime horizon, apixaban resulted in lower costs to the health system (Can$7902.98 v. Can$14 875.82) and an improvement in QALYs (9.089 v. 9.006). The key driver of cost–effectiveness results was the relative risk of VTE as a result of apixaban. Results from the probabilistic analysis showed that at a willingness to pay of Can$50 000 per QALY, the strategy with the highest probability of being most cost-effective was apixaban, with a probability of 99.87%.Interpretation:We found that apixaban is a cost-saving option for the primary thromboprophylaxis of ambulatory patients with cancer who are starting chemotherapy and are at intermediate-to-high risk of VTE.

Patients with cancer are 4–7 times more likely to acquire venous thromboembolism (VTE) than the general population, ¹ based on the hypercoagulable state associated with the cancer itself, patient characteristics and antineoplastic treatments. ² Despite this increased risk for VTE, clinical guidelines do not recommend the use of primary thromboprophylaxis in unselected ambulatory patients with cancer,^3–5 because this strategy has been associated with a small absolute reduction in symptomatic VTE and a nonstatistically significant trend in increased major bleeding events.⁶The Khorana score uses the cancer type and individual patient characteristics to predict the risk of VTE in patients who are about to begin chemotherapy.⁷ This score has been evaluated prospectively for its capacity to identify patients with cancer who are at higher risk for VTE and, therefore, may be used to select those patients who are more likely to benefit from primary thromboprophylaxis.^8,9 The 2019 Apixaban for the Prevention of Venous Thromboembolism in High-Risk Ambulatory Cancer Patients (AVERT) trial assessed the use of a low-dose direct oral factor Xa inhibitor (apixaban 2.5 mg twice daily) for primary thromboprophylaxis in ambulatory patients with cancer who were starting chemotherapy and were at intermediate-to-high risk of VTE (with a Khorana score ≥ 2).¹⁰ The study found that patients randomly assigned to apixaban had a significantly lower risk of VTE compared with placebo. The study also reported that apixaban was not associated with an increase in major bleeding during the on-treatment period. Subsequent to the published results of the AVERT trial and the Efficacy and Safety of Rivaroxaban Prophylaxis Compared with Placebo in Ambulatory Cancer Patients Initiating Systemic Cancer Therapy and at High Risk for Venous Thromboembolism (CASSINI) trial,¹¹ clinical guideline recommendations were updated to endorse the consideration of primary thromboprophylaxis in high-risk ambulatory patients with cancer (Khorana score ≥ 2) before the start of chemotherapy. ^4,5 Given the novelty of this recommendation and supporting data, individualized discussions regarding the risk of bleeding, expected benefits and overall costs are also encouraged.To provide a better framework to support societal discussions on primary thromboprophylaxis in this patient population, we aimed to compare the health system costs and health benefits associated with the use of apixaban primary thromboprophylaxis with those associated with the current standard of care (where no primary thromboprophylaxis is given), from the perspective of Canada’s publicly funded health care system.