COST-EFFECTIVENESS OF PHARMACOGENETIC-BASED DOSING OF WARFARIN IN PATIENTS WITH ATRIAL FIBRILLATION

Purpose: Variants in the genes involved in warfarin metabolism and sensitivity affect individual warfarin requirements and the risk of bleeding.  Testing for these variant alleles might allow more personalized dosing of warfarin during the initiation phase. In 2007 the US Federal Drug Administration changed the labeling for Coumadin™/warfarin to suggest that clinicians consider genetic testing before initiation. We examined the cost-effectiveness of a genotype-guided dosing strategy versus standard induction of warfarin for patients with non-valvular atrial fibrillation (AF).

 Methods: We used a Markov state transition decision model.  Effectiveness and costs were measured in quality-adjusted life years (QALYs) and 2007 U.S. dollars, respectively. Data sources included the English language literature using MEDLINE searches and bibliographies from selected articles, along with empirical data from our institution. The base case focused on a 69-year-old man with newly diagnosed non-valvular atrial fibrillation. Interventions were: standard warfarin initiation vs. initiation guided by genotype of key alleles(CYP2C9*2, CYP2C9*3, and VKORC1-1639 G>A.

 Results: In the base case, genotype-guided dosing resulted in better outcomes but at a high cost.  Overall, the marginal cost-effectiveness of testing was almost $200,000 per QALY.  However, sensitivity analyses revealed that genetic testing would be cost effective under favorable assumptions:  prevention of > 25% of major bleeds, availability within 24 hours, and cost < $200.

 Conclusion: While the cost-effectiveness of genotype-guided dosing appears to significantly exceed a willingness-to-pay threshold of $50,000 per QALY, if future studies demonstrate efficacies above 25% in preventing major bleeds during warfarin initiation and  turnaround times of 24 hours or less, then genotyping would be cost-effective at a cost of < $200/test.