HIT or Miss? Comparing Cost-Effectiveness of Fondaparinux, Argatroban, and Bivalirudin for Heparin-Induced Thrombocytopenia

Two non-heparin anticoagulants have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of heparin-induced thrombocytopenia (HIT): the direct thrombin inhibitors argatroban and bivalirudin. Recent research suggests that fondaparinux, an indirect factor Xa inhibitor, is a safe and effective alternative agent for the treatment of HIT. Data comparing the cost-effectiveness of these agents, though, are lacking.

Ahmed Aljabri, PharmD, from the Center for Health Outcomes and Pharmacoeconomic Research at the University of Arizona in Tucson, and authors performed a cost-effectiveness analysis of these three anticoagulants for the management of suspected HIT – focusing on the institutional costs associated with managing the adverse events of venous thromboembolism (VTE) and major bleeding, laboratory costs, drug administration time, and drug costs.

“The FDA-approved options for managing HIT are expensive, need to be administered intravenously, and require frequent laboratory monitoring and dose adjustment,” Brian Erstad, PharmD, a co-author of the study told ASH Clinical News. “Fondaparinux is increasingly being considered as an alternative agent for suspected or confirmed HIT since it is administered as a once daily subcutaneous injection and requires less frequent laboratory monitoring.”

The authors used a decision-tree model to simulate a hypothetical patient cohort and calculate outcomes in 2016 U.S. dollars. The patient population in this pharmacoeconomic analysis was limited to adult men and non-pregnant, non-breastfeeding women with creatinine clearance >50 mL/minute and suspected or confirmed HIT (defined as a 4T score ≥4 with a positive enzyme-linked immunosorbent assay optical density >0.4 and a confirmed platelet serotonin-release assay).

Six days of therapy was budgeted based on diagnostic test results and an assumed best-case scenario of platelet recovery (150×109/L). In their analyses, the researchers assumed that the cost of managing gastrointestinal bleeding (the most common type of major bleeding observed in relevant trials) was equal to the cost of managing major bleeding.

To calculate the assumed total daily doses of each treatment, the authors considered an average body weight of North American adults to be 80.7 kg, which resulted in the following assumed total daily doses of each treatment:

  • 58.2 mg of argatroban
  • 288 mg of bivalirudin
  • 7.5 mg of fondaparinux

Drug costs were based on those observed at the Banner-University Medical Center in Tucson, Arizona, where a 250 mg/2.5 mL vial of argatroban costs $331; a 250 mg/5 mL vial of bivalirudin costs $418; and a 7.5 mg prefilled syringe of fondaparinux costs $32.72.

Results from the analyses, which accounted for institutional costs and average wholesale price, showed that the cost-savings was greater with fondaparinux compared with both argatroban and bivalirudin. For example, fondaparinux cost $151 in the primary case-base analysis, while bivalirudin and argatroban cost $1,466 and $1,250, respectively. Notably, the rates of adverse events averted (AEA) were similar among all agents used, with fondaparinux showing a slight advantage (TABLE).

Dr. Aljabri and authors also performed probabilistic sensitivity analyses with 2,000 simulations, the results of which confirmed the results of the analyses. For instance, when a longer duration of treatment (9 days) was used, the institutional cost estimates and AEA were $164 (0.9986) for fondaparinux, $1,326 (0.9953) for argatroban, and $1,562 (0.9946) for bivalirudin.

A one-way sensitivity efficacy analysis, in which the baseline rate of AEs was decreased by ≥75 percent for argatroban and ≥80 percent for bivalirudin, also revealed that “even with substantial improvements in the efficacy profile of argatroban and bivalirudin, our study indicates that fondaparinux would prevail cost savings,” the authors wrote. The incremental cost-effectiveness ratio was >$12.7 million for argatroban compared with fondaparinux and >$13 million for bivalirudin compared with fondaparinux.

“Our data strongly suggest potential cost savings with fondaparinux versus argatroban or bivalirudin for anticoagulant prophylaxis in patients with suspected HIT,” Dr. Erstad said. “Considering the three agents’ efficacy and safety profiles, the cost-savings, and AEA by a once-daily fondaparinux subcutaneous injection with limited laboratory monitoring is more advantageous than continuous titration of argatroban or bivalirudin infusions. Greater consideration should be given to fondaparinux as a first-line agent for treatment of suspected HIT.”

The study is limited because the assumed rates of complications were based on published literature that consisted of relatively small trials with a range of reported complications. The authors also noted that “prospective, head-to-head trials are needed to confidently evaluate the relative clinical benefits.”

This analysis also did not account for the indirect medical costs, such as nursing care related to ongoing IV infusion with dose titration and institutional differences in laboratory monitoring costs, which the authors noted “are difficult to quantify accurately and sensitive to local health-care market and labor force dynamics. … Institutions considering adopting fondaparinux as a first-line agent for the treatment of suspected HIT may want to apply our estimates to their local costs.”


Reference

Aljabri A, Huckleberry Y, Karnes J, et al. Cost-effectiveness of anticoagulants for the management of suspected heparin-induced thrombocytopenia in the US. Blood. 2016 October 28. [Epub ahead of print]

TABLE. Cost-Effectiveness Analysis on Institutional Costs Versus Average Wholesale Price
Institutional Costs
  Primary base-case analysis PSA
Drug Cost AEA Cost AEA
Argatroban $1,250 0.9957 $1,186 0.9957
Bivalirudin $1,466 0.9947 $1,400 0.9947
Fondaparinux $151 0.9989 $151 0.9989
Average Wholesale Price
  Secondary base-case analysis PSA
Drug Cost AEA Cost AEA
Argatroban $3,081 0.9957 $3,017 0.9958
Bivalirudin $2,187 0.9947 $2,121 0.9948
Fondaparinux $555 0.9989 $555 0.9989
PSA = probabilistic sensitivity analyses; AEA = adverse event averted

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