BACKGROUND: A recent clinical trial has demonstrated that patients with acute 
coronary syndromes (ACS) and the reduced function allele CYP2C19*2 (*2 allele), 
who are treated with thienopyridines, have an increased risk of adverse cardiac 
events with clopidogrel, but not with prasugrel. The frequency of the *2 allele 
varies by ethnicity and the Maoris, Asians and Pacific Islanders of New Zealand 
have a relatively high incidence.
OBJECTIVE: Our objective was to evaluate, from a New Zealand health system 
perspective, the cost effectiveness of treating all ACS patients with generic 
clopidogrel compared with prasugrel, and also compared with the genetically 
guided strategy that *2 allele carriers receive prasugrel and non-carriers 
receive clopidogrel.
METHODS: A decision-tree model consisting of five health states (myocardial 
infarction, stroke, bleeding, stent thrombosis and cardiovascular death) was 
developed. Clinical outcome data (two TRITON-TIMI 38 genetic sub-studies) 
comparing clopidogrel and prasugrel for both *2 allele carriers and non-carriers 
were combined with the prevalence of the heterozygosity for the *2 allele in New 
Zealand Europeans (15%), Maoris (24%), Asians (29%) and Pacific Islanders (45%) 
to determine the predicted adverse event rate for the New Zealand population. 
National hospital diagnosis-related group (DRG) discharge codes were used to 
determine alternative adverse event rates, along with the costs of 
hospitalizations during the 15 months after patients presented with an ACS. The 
primary outcome measure was the incremental cost per QALY (calculated using 
literature-reported weights). Monte Carlo simulations and alternative scenario 
analysis based on both clinical trial and national hospital incidence were used. 
Additional analysis considered the overall TRITON-TIMI 38 rates. Costs (in New 
Zealand dollars [$NZ], year 2009 values) and benefits were discounted at 3% per 
annum.
RESULTS: Actual hospital-based adverse event rates were higher than those 
reported in the TRITON-TIMI 38 randomized controlled trial and the genetic 
sub-studies, especially for myocardial infarction and cardiovascular death, and 
for Maoris and Pacific Islanders. For both sources of adverse event rates, 
treating the population with prasugrel was associated with worse outcomes 
(QALYs) than clopidogrel. However, prasugrel became cost effective 
($NZ31 751/QALY) when the overall TRITON-TIMI 38 rates were used. A genetic test 
to guide the selected use of prasugrel was cost effective ($NZ8702/QALY versus 
$NZ24 617/QALY) for hospital and clinical trial incidence, respectively. Based 
on the hospital rates, the genetically guided strategy was especially cost 
effective for Maoris ($NZ7312/QALY) and Pacific Islanders ($NZ7041/QALY). These 
results were robust to the sensitivity analysis, except the genetically guided 
strategy under the 15-month clinical trial event rate scenario ($NZ168 748/QALY) 
did not remain cost effective under a $NZ50 000 threshold.
CONCLUSIONS: Use of a genetic test to guide thienopyridine treatment in patients 
with ACS is a potentially cost-effective treatment strategy, especially for 
Maoris and Pacific Islanders. This treatment strategy also has the potential to 
reduce ethnic health disparities that exist in New Zealand. However, the results 
comparing clopidogrel and prasugrel are sensitive to whether the genetic 
sub-studies or the overall TRITON-TIMI 38 rates are used. While the national 
hospital event rates may be more appropriate for the New Zealand population, 
many assumptions are required when they are used to adjust the genetic 
sub-studies rates.