Abstract 14288: ReAssessment of Anti-Platelet Therapy Using an Individualized Strategy Based on Genetic Evaluation Facilitated by a Point-Of-Care Genetic Test (RAPID GENE): A Randomized Proof-Of-Concept Study
Background: Increased rates of major adverse cardiovascular events following percutaneous coronary intervention (PCI) in individuals receiving clopidogrel have been associated with the CYP2C19*2 allele. Ultra rapid identification of CYP2C19*2 carriers with subsequent alteration of anti-platelet therapy would be integral for development of pharmacogenomic strategies. To date, there has been no prospective evaluation of this strategy.
Methods: We developed and validated a point-of-care genetic test for the CYP2C19*2 allele and then evaluated its feasibility in the clinical setting through a prospective proof-of-concept randomized controlled trial designed to examine the potential efficacy of a pharmacogenomic approach following PCI. Patients were randomized to either a strategy of rapid genotyping with selective administration of prasugrel 10mg daily to CYP2C19*2 carriers or to standard therapy with clopidogrel 75 mg daily. Efficacy of the treatment strategies was evaluated using platelet function testing with the VerifyNow P2Y12 reactivity unit (PRU) assay. The primary endpoint is the proportion of CYP2C19*2 carriers with a PRU of > 234 (high on-treatment platelet reactivity) in the rapid genotyping arm compared to those in the standard therapy arm after a 7-day course of dual anti-platelet therapy.
Results: The pre-clinical phase of the study demonstrated 100% sensitivity and specificity of the CYP2C19*2 point-of-care test. To date, 149 patients have been randomized into RAPID GENE. Among enrolled patients, the baseline demographics include: mean age of 59.7±8.9, 26.2% with diabetics, 25.5% smokers, 63.8% with hypertension and 83.2% with hypercholesterolemia. Mean PRU at baseline was 149.7±98.4 compared to Day 7 PRU at 148.5±79.4. Percentage platelet inhibition was 52.5±37.8% and 49.1±24.4% at baseline and Day 7 respectively. Results by randomization arms will analyzed after complete enrollment of the 200 patients, based on initial power calculations. (Projected completion in July 2011)
Conclusions: We report the development of the first point-of-care genetic testing device in medicine and demonstrate its feasibility for use in the routine clinical setting. Full results will be presented at the AHA 2011 meeting.
- © 2011 by American Heart Association, Inc.