Extended Dalteparin Prophylaxis for Venous Thromboembolic Events

Deep vein thrombosis (DVT) and pulmonary embolism (PE) are manifestations of venous thromboembolic events (VTEs). Patients undergoing major surgical procedures such as total hip replacement (THR), total knee replacement (TKR), and hip fracture surgery (HFS) are at an elevated risk for VTEs. The American College of Chest Physicians’ (ACCP) guidelines recommend that such patients receive thromboprophylaxis for at least 10 days. In patients undergoing THR or HFS, extended prophylaxis for up to 28–35 days is the recommended approach for those at high risk of thromboembolic events. The NAFT (North American Fragmin Trial) compared the prophylactic efficacy of dalteparin with that of warfarin during the in-hospital period, and with that of placebo during the period of hospital discharge until day 35 postsurgery, in patients who underwent total hip arthroplasty. During both the in-hospital and the post-discharge time periods, dalteparin significantly reduced the occurrence of DVT. Given the clinical relevance of these results, the low specificity of the ACCP recommendations regarding optimal prophylaxis duration, and the importance of optimizing the efficiency of DVT prophylaxis in the practice setting, a cost-utility analysis was conducted comparing dalteparin 10-day and 35-day (extended) with a warfarin 10-day protocol, in patients undergoing major orthopedic surgeries such as THR, TKR, or HFS.

A three-arm decision model was developed using the prevalence of symptomatic DVT from NAFT publications, epidemiologic studies, and published meta-analyses. Healthcare resource use was abstracted from a survey of clinicians and from the economic literature. Utility estimates were obtained by interviewing a sample of 24 people from the general public using the time trade-off technique. The clinical, economic and utility data were then used to estimate the cost per quality-adjusted life-year (QALY) gained with dalteparin for 10 or 35 days relative to 10 days of warfarin.

Canadian provincial healthcare system.

The cost per QALY gained with 10 days of dalteparin was below $Can1000 for all the surgeries evaluated (all costs are reported in 2007 Canadian dollars [$Can1 = $US1, as of December 2007]). In the case of extended prophylaxis, the incremental cost per QALY gained with 35 days of dalteparin over warfarin was $Can40 100, $Can46 500, and $Can31 200 for patients undergoing THR, TKR, and HFS, respectively. Reducing the duration of prophylaxis from 35 to 28 days generated ratios that were below $Can35 000 for all three surgeries evaluated.

Ten days of dalteparin following major orthopedic surgery is a clinically and economically attractive alternative to warfarin for DVT prophylaxis. In the case of the 35-day dalteparin protocol, the results also indicated acceptable economic value to a publicly funded healthcare system, particularly in the settings of HFS and THR. In addition, reducing the duration of prophylaxis to 28 days postsurgery would be associated with a more favorable return on public healthcare expenditures.