The EPCAT (Extended Prophylaxis Comparing low molecular weight heparin to Aspirin following Total hip arthroplasty) study demonstrated that after patients received an initial 10-day post-operative course of LMWH, extending prophylaxis for an additional 28 days with aspirin was at least as effective and safe as low molecular weight heparin (LMWH) for the prevention of venous thromboembolism (VTE) following elective total hip arthroplasty (Anderson et al Ann Intern Med 2013). However, the cost-effectiveness of aspirin relative to LMWH in this setting is unclear. Based on the EPCAT results, we evaluated the cost-effectiveness of extended aspirin versus LMWH prophylaxis in terms of incremental cost per quality-adjusted life year (QALY) gained.
In the EPCAT study, following total hip arthroplasty all patients received 10 days of LMWH (dalteparin 5000 u SQ daily). Patients were then randomized to continue dalteparin or begin aspirin 81 mg daily for an additional 28 days. In the 90-day follow up period after randomization 1 of 380 (0.3%) patients randomized to aspirin compared to 5 of 398 receiving LMWH developed VTE complications (difference 1.0%; 95% CI -0.5 to 2.5%). Clinically significant bleeding occurred in 2 aspirin patients (0.5%) and 5 patients (1.3%) receiving LMWH (difference 0.72; 95% CI -0.83 to 2.3%). A decision tree was constructed to describe the short and long-term health and cost consequences of each regimen, including the presence or absence of VTE or bleeding, the particular type of VTE (deep vein thrombosis (DVT) or pulmonary embolism (PE)) or bleeding (major or clinically important non-major), and whether or not the outcome was fatal. Event probabilities were derived from the EPCAT study. Outpatient treatment protocols were based on expert opinion, with costs from the 2012 Nova Scotia fee schedule and hospital charges. The costs of inpatient management of DVT, PE and clinically significant bleeding were based upon the Ontario Case Costing Initiative (OCCI) estimates of average case costs from 2006/07. Daily drug costs were derived from a pooled sample of prices from 6 retail pharmacies in 3 Canadian provinces. All costs were inflated to 2013 Canadian (CAD) dollars ($) based on the Statistics Canada Consumer Price Index, Health Component. Health state utilities were derived from the literature. Probabilistic sensitivity analysis and one-way threshold analyses were conducted to test the robustness of the results.
Based on point estimates from the EPCAT study, aspirin was associated with cost savings of CAD442 per patient (95% CI $383 to $628) and a very small gain of 0.9 QALYs per 1000 patients (95% CI 0.3 to 1.6 per 1000 patients) treated relative to LMWH. Aspirin was dominant (more effective and less costly) in >95% of the iterations of the probabilistic sensitivity analysis. The EPCAT study data demonstrated that the relative risk of VTE with aspirin compared to LMWH was 0.21, but threshold analysis showed that aspirin would still be cost-saving relative to LMWH with a relative risk for VTE over 12.0. Similarly, in the EPCAT study, the relative risk of bleeding with aspirin was 0.45, but our analysis indicated it remained cost-saving including a relative risk over 6.0 of clinically important bleeding.
Extended prophylaxis for 28 days with aspirin was non-inferior to and as safe as LMWH for the prevention of VTE following total hip arthroplasty after patients received LMWH for 10 days. Based on this clinical data, use of aspirin was cost-saving and economically dominant compared to LMWH. Threshold analysis suggested that this conclusion remained robust across large plausible ranges of VTE and bleeding rates.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.