Cost-Effectiveness of Genotype-Guided Warfarin Dosing for Patients With Atrial Fibrillation

Abstract

Background-CYP2C9 and VKORC1 genotyping has been advocated as a means of improving the accuracy of warfarin dosing. However, the effectiveness of genotyping in improving anticoagulation control and reducing major bleeding has not yet been compellingly demonstrated. Genotyping currently costs $400 to $550. Methods and Results-We constructed a Markov model to evaluate whether and under what circumstances geneticallyguided warfarin dosing could be cost-effective for newly diagnosed atrial fibrillation patients. Estimates of clinical event rates, treatment and adverse event costs, and utilities for health states were derived from the published literature. The cost-effectiveness of genetically-guided dosing was highly dependent on the assumed effectiveness of genotyping in increasing the amount of time patients spend appropriately anticoagulated. If genotyping increases the time spent in the target international normalized ratio range by Ͻ5 percentage points, its incremental cost-effectiveness ratio would be greater than $100 000 per quality-adjusted life year. The incremental cost-effectiveness ratio falls below $50 000 per quality-adjusted life year if genotyping increases the time spent in range by 9 percentage points. The results were also sensitive to assumptions about the rate of major bleeding events during treatment initiation and the cost of the test. Conclusions-Our results suggest that genotyping before warfarin initiation will be cost-effective for patients with atrial fibrillation only if it reduces out-of-range international normalized ratio values by more than 5 to 9 percentage points compared with usual care. Given the current uncertainty surrounding genotyping efficacy, caution should be taken in advocating the widespread adoption of this strategy.

Meta-analysis of Randomized Controlled Trials of Genotype-Guided vs Standard Dosing of Warfarin

“…Given the results of this meta-analysis, CHEST should make the recommendation to consider genotyping, as it has improved % TTR and reduced major bleeding, although it did not change thrombotic outcomes or overall mortality. Prior cost-eff ectiveness analyses showed genotype guidance to be cost-eff ective compared with standard dosing if it resulted in 5% to 9% higher TTR 51 and 32% lower risk of major bleeding. 52 Th e current meta-analysis resulted in about a 6% increase in TTR and 66% reduction in relative risk of major bleeding.…”

Financial Analysis of CYP2C19 Genotyping in Patients Receiving Dual Antiplatelet Therapy Following Acute Coronary Syndrome and Percutaneous Coronary Intervention

“…While the relatively high cost of a CYP2C9 and VKORC1 bundled test ($326 to $570) resulted in only modest improvements (quality-adjusted lifeyears, survival rates, and total adverse rates), investigators also suggested that improvements in the cost-effectiveness can be achieved through further cost reduction of the genotyping test and utilizing a genotype-guided warfarin dosing algorithm in outliers (patients with out-of-range international normalized ratios and/or those who are at high risk for hemorrhage). 22,23 Other variables, such as different population prevalence of a specific variant and cost of alternative treatment approaches, would also impact the economic impact analysis. Ultimately, clinical utility and cost-effectiveness cannot solely determine the relative value of pharmacogenetic testing in optimizing drug therapy for individual patients.…”

Cost-Effectiveness of Apixaban Compared With Aspirin for Stroke Prevention in Atrial Fibrillation Among Patients Unsuitable for Warfarin

“…5 Other sources of probabilities included published studies of anticoagulation [6][7][8][9][10][11][12] identified through searches of Medline and the Tufts Cost-Effectiveness Analysis Registry 13 and a review of previous economic models. [14][15][16][17] The model simulated the progression of a hypothetical cohort of 70-year-old patients with AF, a CHADS 2 score of 2 (congestive heart failure, 1 point; hypertension defined as blood pressure consistently >140/90 mmHg or antihypertension medication, 1 point; age >75 years, 1 point; diabetes mellitus, 1 point; previous stroke or transient ischemic attack, 2 points) and a low-risk of bleeding, who initiated pharmacological stroke prevention with either apixaban (5 mg twice daily) or aspirin (81-324 mg daily).…”