Reassessment of Anti-Platelet Therapy Using an Individualized Strategy Based on Genetic Evaluation - RAPID GENE

Apr 03, 2012
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Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Spartan Biosciences
Date Presented:
01/01/2011
Date Published:
01/01/2012
Date Updated:
04/03/2012
Original Posted Date:
04/03/2012
References

Description:

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).

Hypothesis:

Selective use of prasugrel, guided by rapid genotyping, will decrease high on-treatment platelet reactivity.

Study Design

  • Randomized
  • Parallel

Patient Populations:

  • 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%

Exclusions:

  • 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
  • Pregnancy

Primary Endpoints:

  • 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

Secondary Endpoints:

  • 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

Drug/Procedures Used:

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.

Concomitant Medications:

At baseline, the use of aspirin was 92%, statin 89%, angiotensin-converting enzyme inhibitor 45%, and beta-blocker 77%.

Principal Findings:

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.

Interpretation:

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.

References:

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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