THRESHOLDS FOR VENOUS THROMBOEMBOLISM PROPHYLAXIS IN HOSPITALIZED MEDICAL PATIENTS — A COST-EFFECTIVENESS ANALYSIS

Background:

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 warrants prophylaxis has not been defined. We used cost-effectiveness analysis to determine a prophylaxis threshold based on risk of VTE.

Methods:

We constructed a decision model consisting of two consecutive modules: a 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, pulmonary emboli, bleeding events, and heparin-induced thrombocytopenia. Long-term complications included recurrent VTE, post-thrombotic syndrome, and pulmonary hypertension. In our base-case analysis, 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.

Results:

Assuming a willingness-to-pay threshold of $100,000/QALY, prophylaxis was indicated for an average medical patient with a VTE risk of ≥1.0%. For the average patient, prophylaxis was not indicated when bleeding risk was >8.1%, patient age was >73.5 years, or the cost of enoxaparin exceeded $60/dose. If VTE risk was <0.26% or bleeding risk was >19%, the harms of prophylaxis outweighed the benefits. The prophylaxis threshold was relatively insensitive to LMWH cost and bleeding risk, but very sensitive to patient age/life expectancy.

Conclusions:

The decision to offer prophylaxis should be personalized based on patient VTE risk and age/life expectancy. Prophylaxis is not warranted for most patients with VTE risk below 1.0%. Prophylaxis represents a net harm in patients whose VTE risk is below approximately 0.26%.