Patrick Amanda R, Avorn Jerry, Choudhry Niteesh K
Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02120, USA.
Circ Cardiovasc Qual Outcomes. 2009 Sep;2(5):429-36. doi: 10.1161/CIRCOUTCOMES.108.808592. Epub 2009 Jul 21.
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.
We constructed a Markov model to evaluate whether and under what circumstances genetically-guided 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 <5 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.
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.
CYP2C9和VKORC1基因分型已被提倡作为提高华法林给药准确性的一种方法。然而，基因分型在改善抗凝控制和减少大出血方面的有效性尚未得到令人信服的证明。目前基因分型的费用为400美元至550美元。
我们构建了一个马尔可夫模型，以评估基因指导的华法林给药对于新诊断的房颤患者是否具有成本效益以及在何种情况下具有成本效益。临床事件发生率、治疗和不良事件成本以及健康状态效用的估计值均来自已发表的文献。基因指导给药的成本效益高度依赖于基因分型在增加患者适当抗凝时间方面的假定有效性。如果基因分型使目标国际标准化比值范围内的时间增加不足5个百分点，其增量成本效益比将超过每质量调整生命年100,000美元。如果基因分型使目标范围内的时间增加9个百分点，增量成本效益比将降至每质量调整生命年50,000美元以下。结果还对治疗开始期间大出血事件的发生率以及检测成本的假设敏感。
我们的结果表明，仅当与常规治疗相比，基因分型能使超出范围的国际标准化比值降低5至9个百分点以上时，在开始使用华法林前进行基因分型对于房颤患者才具有成本效益。鉴于目前基因分型疗效存在不确定性，在提倡广泛采用这一策略时应谨慎。
