OBJECTIVES:
Cytochrome P450 2C19 (CYP2C19) genotype has been shown to affect cardiovascular (CV) outcomes for clopidogrel but not prasugrel. This study evaluates the cost-effectiveness of CYP2C19-guided vs. routine antiplatelet therapy in ACS patients.
METHODS:
We constructed a literature-based, decision analytic, Markov model (TreeAge 2009) to estimate the cost-effectiveness of CYP2C19-guided aspirin plus either clopidogrel or prasugrel therapy vs. no genotyping. Post-initial ACS CV events were based on the TRITON-TIMI 38 study and related costs were derived primarily using 2007 Healthcare Cost and Utilization Project DRGs for nonfatal MI and stroke, CV death, intracranial hemorrhage, other life-threatening bleed, and minor bleed. Additional costs and disease-state utilities were obtained from other published sources. All costs were adjusted to 2009 $US using the Consumer Price Index medical care component. The model allowed for clopidogrel/prasugrel discontinuation and aspirin monotherapy. Model sensitivity was assessed using 1-way and multi-way analysis of influential parameters.
RESULTS:
The base case model demonstrated that CYP2C19 genotype guided antiplatelet therapy yielded lower overall annual cost and greater efficacy vs. no genotyping (
Table
). The model was sensitive to (in declining order): clopidogrel cost/day ($1 to $5.78), prasugrel cost/day ($4.09 to $ 6.81), % CYP2C19 extensive metabolizers on clopidogrel (60% to 100%), CYP2C19 test cost ($60 to $250), and monthly CV event management cost. A threshold value for clopidogrel at <$2.14/day favored the no genotyping strategy. However, the genotyping strategy was dominant when clopidogrel cost =$1/day and a CYP2C19 test cost threshold of <$125 on 2-way analysis.
CONCLUSIONS:
CYP2C19 genotype-guided clopidogrel or prasugrel therapy is cost-effective for up to 1 year in ACS patients, and can remain a preferred strategy at a hypothetical generic clopidogrel cost of $1.00/day.
Table
Strategy1
Annual Cost
Incremental Cost
Quality Adjusted Life Year (QALY)
Incremental QALY
Cost/QALY
Incremental Cost Effectiveness (ICER)
CYP2C19 Genotype-Guided
$ 3,211
0.7212
$ 4,452
No Gentoyping
$ 3,331
$120
0.6767
- (0.0445)
$ 4,921
(Dominated)
1Base case values:Drug wholesale acquisition cost/day: clopidogrel $4.62, prasugrel $5.45; Baseline post-ACS utility = 0.83; Monthly cost for post-CV event management = $351; CYP2C19 genotyping =$185; After genotyping: 80% of extensive metabolizers, 20% of intermediate metabolizers and 10% of poor metabolizers on clopidogrel; 80% on clopidogrel without genotyping; Willingness to pay = $200
Serum interleukin-18 levels as a predictor for patients with genetic dysfunction of cytochrome P450 2C19 in dual antiplatelet therapy with clopidogrel
