Cost-effectiveness of CYP2C19 genotyping to guide antiplatelet therapy for acute minor stroke and high-risk transient ischemic attack


Abstract

Dual antiplatelet therapy (DAPT) with clopidogrel plus aspirin within 48 h of acute minor strokes and transient ischemic attacks (TIAs) has been indicated to effectively reduce the rate of recurrent strokes. However, the efficacy of clopidogrel has been shown to be affected by cytochrome P450 2C19 (CYP2C19) polymorphisms. Patients carrying loss-of-function alleles (LoFAs) at a low risk of recurrence (ESRS < 3) cannot benefit from clopidogrel plus aspirin at all and may have an increased bleeding risk. In order to optimize antiplatelet therapy for these patients and avoid the waste of medical resources, it is important to identify the subgroups that genuinely benefit from DAPT with clopidogrel plus aspirin through CYP2C19 genotyping. This study sought to assess the cost-effectiveness of CYP2C19 genotyping to guide drug therapy for acute minor strokes or high-risk TIAs in China. A decision tree and Markov model were constructed to evaluate the cost-effectiveness of CYP2C19 genotyping. We used a healthcare payer perspective, and the primary outcomes included quality-adjusted life years (QALYs), costs and the incremental cost-effectiveness ratio (ICER). Sensitivity analyses were performed to evaluate the robustness of the results. CYP2C19 genotyping resulted in a lifetime gain of 0.031 QALYs at an additional cost of CNY 420.13 (US$ 59.85), yielding an ICER of CNY 13,552.74 (US$ 1930.59) per QALY gained. Probabilistic sensitivity analysis showed that genetic testing was more cost-effective in 95.7% of the simulations at the willingness-to-pay threshold of CNY 72,100 (GDP per capita, US$ 10,300) per QALY. Therefore, CYP2C19 genotyping to guide antiplatelet therapy for acute minor strokes and high-risk TIAs is highly cost-effective in China.

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
One-way sensitivity analyses on incremental cost-effectiveness ratio (ICER) gained by genetic testing. Numbers listed in parentheses indicate the range of the variable. Dark-shaded bars represent the lower bound of the variable range. Light-shaded bars represent the upper bound. Solid vertical lines represent the ICER of the clopidogrel-aspirin regimen at the base-case scenario (CNY 13,552.74/QALY). QALYs, quality adjusted life years.
Figure 2
Figure 2
Incremental cost-effectiveness scatterplot of the result of the probabilistic sensitivity analysis. The dashed line represents the willingness-to-pay threshold of CNY 105,000 per QALY. The white square represents the base-case (0.031 QALYs gained at an incremental cost of CNY 420.13). CNY, Chinese Yuan Renminbi; QALYs, quality adjusted life years; WTP, willingness-to-pay.
Figure 3
Figure 3
Cost-effectiveness acceptability curve and frontier; y-axis values indicate the probability of a strategy being cost-effective across a wide range of willingness-to-pay thresholds. The solid vertical line represents the willingness-to-pay threshold of CNY 216,000 per QALY. The dashed vertical line represents CNY 72,100 per QALY. CNY, Chinese Yuan Renminbi.
Figure 4
Figure 4
Model structure of cost-effectiveness analysis. (A) is the decision tree model within 90?days, and (B) is the long-term Markov model. Locations in the model where prescribers can make a decision (squares), chance nodes that are under the control of transition probabilities (circles), and terminal nodes (triangles) are presented. Transitions to future health states leading from the other health states are the same as for the minor or no disability branch. ECH extracranial hemorrhage, ICH intracerebral hemorrhage, MI myocardial infarction.
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