Abstract
Background
Direct oral anticoagulants (DOACs) are at least as effective as low-molecular weight heparins (LMWH) at preventing recurrence after cancer-associated venous thromboembolism (CA-VTE). DOACs are also oral and far less costly, but they may confer a higher bleeding risk than LMWH.
Purpose
To estimate the cost-effectiveness of DOACs and LMWHs for CA-VTE.
Methods
We developed a health state transition model to estimate recurrent VTE, bleeding events, quality-adjusted life years (QALY), and direct healthcare costs (2018 United States dollars) associated with DOACs vs. LMWH use. The model had four states: (1) long-term anticoagulation (first 3 months after VTE), (2) extended anticoagulation (more than 3 months after VTE), (3) off anticoagulants, and (4) death. We used a United States healthcare sector perspective, 3-month cycle length, and 1-year time horizon. Event probabilities were derived from the Hokusai Cancer VTE trial and other literature. Event and medication costs were obtained from national sources. We used a threshold of less than $50,000 per QALY gained to define cost-effectiveness.
Results
Compared to LMWH, DOACs were less costly (mean costs: $8,477 vs. $33,917 per year) and similarly effective (mean QALY: 0.616 vs. 0.622). The incremental cost-effectiveness ratio was $4,479,374 per QALY gained with LMWH, indicating that DOACs are cost-effective (Table 1). In threshold analyses, LMWH therapy only became cost-effective when DOAC recurrent VTE risk increased to at least 72% (relative risk vs. LMWH, 6.19) or DOAC clinically relevant bleeding increased to at least 39% (relative risk vs. LMWH, 10.09).
Scenarios Recurrent VTE, % Major bleed, % Mean difference DOAC − LMW ICER DOAC LMWH Relative Risk DOAC LMWH Relative Risk Cost QALY Base case 8.1 11.6 0.71 6.8 4.0 1.75 −$25,440 (−26,496, −24,274) −0.006 (−0.019, 0.008) $4,479,374 DOAC outcome rate threshold at which LMWH becomes cost-effective* Recurrent VTE 71.5 11.7 6.19 – – – −$6,064 (−7,534, −4,627) −0.121 (−0.136, −0.108) $49,886 Major Bleed – – – 38.9 4.0 10.09 −$2,192 (−3,400, −704) −0.044 (−0.056, −0.030) $49,878 DOAC = direct oral anticoagulant, ICER = incremental cost-effectiveness ratio, LMWH = low-molecular-weight heparin, VTE = venous thromboembolism. Values are mean (95% Uncertainty Interval). Uncertainty was derived from 1,000 stochastic model iterations. *Represents the minimum increased risk with DOAC that would result in LMWH achieving an ICER <$50K per QALY gained.
Conclusion
In this simulation study, DOACs were a cost-effective oral alternative to LMWH for the treatment of CA-VTE. For LMWH to be cost-effective, DOAC event rates needed to be far higher than what is likely to be observed in clinical practice.
Acknowledgement/Funding
Agency for Health Research and Quality R18HS026156
Safety and efficacy of direct oral anticoagulants (DOACs) vs low molecular weight heparin (LMWH) in malignancy induced venous thromboembolism-a systematic review and meta analysis
