title: Cost effectiveness of targeted high-dose atorvastatin therapy following genotype testing in patients with acute coronary syndrome.
abstract: BACKGROUND
  Results from the PROVE IT trial suggest that patients with acute coronary syndrome (ACS) treated with atorvastatin 80 mg/day (A80) have significantly lower rates of cardiovascular events compared with patients treated with pravastatin 40 mg/day (P40). In a genetic post hoc substudy of the PROVE IT trial, the rate of event reduction was greater in carriers of the Trp719Arg variant in kinesin family member 6 protein (KIF6) than in noncarriers. We assessed the cost effectiveness of testing for the KIF6 variant followed by targeted statin therapy (KIF6 Testing) versus not testing patients (No Test) and treating them with P40 or A80 in the USA from a payer perspective.
  
  
  METHODS
  A Markov model was developed in which 2-year event rates from PROVE IT were extrapolated over a lifetime horizon. Costs and utilities were derived from published literature. All costs were in 2010 US dollars except the cost of A80, which was in 2012 US dollars because the generic formulation was available in 2012. Expected costs and quality-adjusted life-years (QALYs) were estimated for each strategy over a lifetime horizon.
  
  
  RESULTS
  Lifetime costs were US$31,700; US$37,100 and US$41,300 for No Test P40, KIF6 Testing and No Test A80 strategies, respectively. The No Test A80 strategy was associated with more QALYs (9.71) than the KIF6 Testing (9.69) and No Test P40 (9.57) strategies. No Test A80 had an incremental cost-effectiveness ratio (ICER) of US$232,100 per QALY gained compared with KIF6 Testing. KIF6 Testing had an ICER of US$45,300 per QALY compared with No Test P40.
  
  
  CONCLUSIONS
  Testing ACS patients for KIF6 carrier status may be a cost-effective strategy at commonly accepted thresholds. Treating all patients with A80 is more expensive than treating patients on the basis of KIF6 results, but the modest gain in QALYs is achieved at a cost/QALY that is generally considered unacceptable compared with the KIF6 Testing strategy. Compared with treating all patients with P40, the KIF6 Testing strategy had an ICER below US$50,000 per QALY. The conclusions from this study are sensitive to the price of generic A80 and the effect on adherence of knowing KIF6 carrier status. The results were based on a post hoc substudy of the PROVE IT trial, which was not designed to test the effectiveness of KIF6 testing.
authors.affiliation: OptumInsight, One Main Street, Suite 1040, Cambridge, MA 02142, USA. anju.parthan@optum.com
authors.forename: Anju
authors.initials: A
authors.lastname: Parthan
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Leahy
authors.forename: Amy K
authors.initials: AK
authors.lastname: O'Sullivan
authors.forename: Olga A
authors.initials: OA
authors.lastname: Iakoubova
authors.forename: Lance A
authors.initials: LA
authors.lastname: Bare
authors.forename: James J
authors.initials: JJ
authors.lastname: Devlin
authors.forename: Milton C
authors.initials: MC
authors.lastname: Weinstein
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000191:economics / Q000235:genetics; D000069059:Atorvastatin; D003362:Cost-Benefit Analysis; D004305:Dose-Response Relationship, Drug; D005260:Female; D005820:Genetic Testing / Q000191:economics / Q000379:methods; D005838:Genotype; D006538:Heptanoic Acids / Q000191:economics / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000191:economics / Q000494:pharmacology / Q000627:therapeutic use*; D016547:Kinesins / Q000235:genetics*; D008297:Male; D008390:Markov Chains; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D017035:Pravastatin / Q000008:administration & dosage / Q000191:economics / Q000627:therapeutic use; D011758:Pyrroles / Q000191:economics / Q000494:pharmacology / Q000627:therapeutic use*; D019057:Quality-Adjusted Life Years
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin; C526774:KIF6 protein, human; D016547:Kinesins; D017035:Pravastatin