Reassessment of Anti-Platelet Therapy Using an Individualized Strategy Based on Genetic Evaluation - RAPID GENE
The goal of the trial was to evaluate a strategy of rapid genotyping for the CYP2C19*2 allele with selective use of prasugrel (in carriers of the CYP2C19*2 allele) compared with standard therapy with clopidogrel (in noncarriers of the CYP2C19*2 allele) among patients undergoing percutaneous coronary intervention (PCI).
Selective use of prasugrel, guided by rapid genotyping, will decrease high on-treatment platelet reactivity.
- Patients 18-75 years of age undergoing PCI for NSTEMI or stable coronary artery disease
Number of enrollees: 200
Duration of follow-up: 1 month
Mean patient age: 60 years
Percentage female: 21%
- Initial treatment with antiplatelet therapy other than aspirin and clopidogrel
- Requirement for anticoagulation therapy
- Prior stroke or transient ischemic attack
- Thrombocytopenia (<100,000/L)
- Bleeding diathesis
- Hematocrit <30% or >52%
- Severe liver disease
- Creatinine clearance <30 ml/min
- Proportion of CYP2C19*2 carriers with a PRU >234 in the rapid genotyping arm compared with CYP2C19*2 carriers in the standard therapy arm at 1 week
- Mean PRU and percentage platelet inhibition among CYP2C19*2 carriers
- Composite of cardiovascular death, nonfatal myocardial infarction, rehospitalization, or stent thrombosis
- Thrombolysis in Myocardial Infarction (TIMI) major bleeding
- TIMI minor bleeding
Patients with non−ST-elevation myocardial infarction (NSTEMI) or stable coronary artery disease undergoing PCI after pretreatment with clopidogrel were randomized to rapid genotyping (n = 102) and selective use of prasugrel guided by carrier status versus standard therapy (n = 98).
Rapid genotyping was performed by buccal swab to identify carriers of the CYP2C19*2 allele.
Carriers of the CYP2C19*2 allele were treated with prasugrel 10 mg daily for 1 week, while noncarriers and the standard therapy group were treated with clopidogrel 75 mg daily for 1 week.
At 1 week, platelet function testing was performed in all patients, while rapid genotyping was performed in the standard therapy group.
At baseline, the use of aspirin was 92%, statin 89%, angiotensin-converting enzyme inhibitor 45%, and beta-blocker 77%.
Overall, 200 patients were randomized. The mean age was 60 years, 21% were women, 25% had diabetes, and mean body mass index was 30 kg/m2. Drug-eluting stents were used in 78%. Of the 102 patients in the rapid genotyping group, 23 (25%) were CYP2C19*2 carriers. Sensitivity and specificity of rapid genotyping at detecting the CYP2C19*2 allele was 100% and 99.3%, respectively.
The primary outcome, P2Y12 reactivity unit (PRU) value >234 occurred in none of the CYP2C19*2 carriers in the rapid genotyping arm compared with 30% of the CYP2C19*2 carriers in the standard therapy arm at 1 week (p = 0.0092).
Mean PRU at 1 week was 75.6 among CYP2C19*2 carriers in the rapid genotyping arm compared with 207.3 among CYP2C19*2 carriers in the standard therapy arm (p < 0.0001). Percent platelet inhibition: 73.3% versus 27.0% (p < 0.0001), respectively.
Major adverse cardiac events (MACE) did not occur in either group at 1 or 4 weeks.
Major bleeding: 2.2% versus 1.0% (p = 0.61), major or minor bleeding: 5.5% versus 2.1% (p = 0.27), respectively.
Among patients with stable or unstable coronary artery disease undergoing PCI, rapid genotyping was effective at identifying CYP2C19*2 carriers. Among CYP2C19*2 carriers, high platelet reactivity was eliminated by treatment with prasugrel compared with clopidogrel. Future studies are needed to determine if rapid genotyping can improve clinical outcomes.
Roberts JD, Wells GA, Le May MR, et al. Point-of-care genetic testing for personalisation of antiplatelet treatment (RAPID-GENE): a prospective, randomised, proof-of-concept trial. Lancet 2012;Mar 28:[Epub ahead of print].
Presented by Dr. Derek So at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2011), San Francisco, CA, November 9, 2011.
Keywords: Coronary Artery Disease, Myocardial Infarction, Follow-Up Studies, Platelet Function Tests, Drug-Eluting Stents, Thiophenes, Ticlopidine, Blood Platelets, Piperazines, Purinergic P2Y Receptor Antagonists, Percutaneous Coronary Intervention, Body Mass Index, Genotype, Diabetes Mellitus
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