USING COST-EFFECTIVENESS ANALYSIS TO DETERMINE A THRESHOLD FOR VENOUS THROMBOEMBOLISM PROPHYLAXIS IN HOSPITALIZED MEDICAL PATIENTS

Purpose: Venous thromboembolism (VTE) is a common preventable condition in hospitalized medical patients. Chemoprophylaxis with heparin or fondaparinux has been recommended for all hospitalized patients who are not at low risk, and appropriate thromboprophylaxis is a hospital quality measure. However, the specific threshold of VTE risk that requires prophylaxis has not been defined. We used cost-effectiveness analysis to determine a threshold for prophylaxis based on risk of VTE.

Method: We constructed a decision model consisting of two consecutive modules: a simple decision-tree that followed patients up to 3 months after hospitalization, and a lifetime Markov model with 3-month cycles. The model tracked symptomatic deep vein thromboses and pulmonary emboli, bleeding events and heparin-induced thrombocytopenia. Long-term complications included recurrent VTE, post-thrombotic syndrome, and pulmonary hypertension. For base-case, we considered medical inpatients aged 66 years, having a life expectancy of 13.5 years, VTE risk of 1.4%, and bleeding risk of 2.7% on average. Patients received enoxaparin 40mg/day for prophylaxis. Transition probabilities, costs and utilities were derived primarily from US-based studies to estimate total costs and quality-adjusted life years (QALYs). The efficacy of enoxaparin was based on a meta-analysis of randomized clinical trials. Costs included direct medical costs and were expressed in 2015 US dollars. The study was conducted from the health system perspective.  Costs and QALYs were discounted at 3%/year. We also conducted sensitivity analyses assuming a willingness-to-pay of $100,000/QALY.

Result: In the base-case, prophylaxis had an incremental cost of $44,091/QALY saved compared to no prophylaxis. In sensitivity analysis, prophylaxis would cost >$100,000/QALY if VTE risk was < 0.85%, bleeding risk was >12%, life expectancy was < 5.4 years, patient's age was >76.5 years, or the cost of LWMH exceeded $86/dose. If VTE risk was <0.2% or bleeding risk was >25%, the harms of prophylaxis outweighed the benefits. The prophylaxis threshold was relatively insensitive to the cost of LMWH and bleeding risk, but very sensitive to life expectancy (figure). In probabilistic sensitivity analysis, prophylaxis had 77% the probability of being cost-effective.  

Conclusion: Prophylaxis seems to be cost-effective for average medical inpatients, but can be personalized based on VTE risk and life expectancy. Prophylaxis is not warranted for most patients with VTE risk below 0.85% or life expectancy less than 5 years.