Cost-effectiveness of CYP2C19-guided antiplatelet therapy in patients with acute coronary syndrome and percutaneous coronary intervention informed by real-world data

Abstract

Current guidelines recommend dual antiplatelet therapy (DAPT) consisting of aspirin and a P2Y12 inhibitors following percutaneous coronary intervention (PCI). CYP2C19 genotype can guide DAPT selection, prescribing ticagrelor or prasugrel for loss-of-function (LOF) allele carriers (genotype-guided escalation). Cost-effectiveness analyses (CEA) are traditionally grounded in clinical trial data. We conduct a CEA using real-world data using a 1-year decision-analytic model comparing primary strategies: universal empiric clopidogrel (base case), universal ticagrelor, and genotype-guided escalation. We also explore secondary strategies commonly implemented in practice, wherein all patients are prescribed ticagrelor for 30 days post PCI. After 30 days, all patients are switched to clopidogrel irrespective of genotype (nonguided de-escalation) or to clopidogrel only if patients do not harbor an LOF allele (genotype-guided de-escalation). Compared with universal clopidogrel, both universal ticagrelor and genotype-guided escalation were superior with improvement in quality-adjusted life years (QALY's). Only genotype-guided escalation was cost-effective ($42,365/QALY) and demonstrated the highest probability of being cost-effective across conventional willingness-to-pay thresholds. In the secondary analysis, compared with the nonguided de-escalation strategy, although genotype-guided de-escalation and universal ticagrelor were more effective, with ICER of $188,680/QALY and $678,215/QALY, respectively, they were not cost-effective. CYP2C19 genotype-guided antiplatelet prescribing is cost-effective compared with either universal clopidogrel or universal ticagrelor using real-world implementation data. The secondary analysis suggests genotype-guided and nonguided de-escalation may be viable strategies, needing further evaluation.

Fig. 1. Decision-analytic model simulating outcomes of five strategies over a 1-year horizon.

The primary strategies were universal clopidogrel (base case), universal ticagrelor, and CYP2C19-guided escalation. The secondary strategies were de-escalation at 30 days (unguided strategy 3; genotype-guided strategy 4).

Fig. 2. Tornado plots of influential factors from the probabilistic sensitivity analyses (PSA).

Tornado plots of fifteen most influential factors from the probabilistic sensitivity analyses (PSA) of universal ticagrelor scenario (a) or genotype escalation scenario (b) compared with the reference scenario, universal clopidogrel. Parameter ranges used in PSA are given in Table 2; parameter values greater than base case are represented in red while values lower than base case are represented in green. Willingness to pay is set to 100,000/QALY. The difference in net monetary benefit on x-axis shows parameter values for which the alternative strategy is cost-effective (difference is positive) or when reference strategy is more cost-effective (difference is negative).

Fig. 3

Cost-effectiveness acceptability curve and frontier; y-axis values indicate probability of a strategy being cost-effective across a wide range of willingness-to-pay thresholds.