Authors
Roberts JD, Wells GA, Le May MR, et al
Title
Point-of-care genetic testing for personalisation of antiplatelet treatment (RAPID-GENE): a prospective, randomised, proof-of-concept trial.
References
Lancet 2012;379:1705-11.
Background
Prospective assessment of pharmacogenetic strategies has been limited by an inability to undertake bedside genetic testing. The CYP2C19*2 allele is a common genetic variant associated with increased rates of major adverse events in individuals given clopidogrel after percutaneous coronary intervention (PCI). We used a novel point-of-care genetic test to identify carriers of the CYP2C19*2 allele and aimed to assess a pharmacogenetic approach to dual antiplatelet treatment (DAPT) after PCI.
Purpose
The objective of the RAPID GENE study is to evaluate the feasibility, efficacy and safety of a pharmacogenomic approach to anti-platelet therapy following coronary artery stenting using a CYP2C19*2 point-of-care genetic test.
Design
Randomized, open-label, parallel assignment safety/efficacy study Prospective proof-of concept study Patients undergoing PCI for acute coronary syndrome or stable angina were randomly assigned to rapid point-of-care genotyping or to standard treatment. Individuals in the rapid genotyping group were screened for the CYP2C19*2 allele. Carriers were given 10 mg prasugrel daily, and non-carriers and patients in the standard treatment group were given 75 mg clopidogrel daily. The primary endpoint was the proportion of CYP2C19*2 carriers with high on-treatment platelet reactivity (P2Y12 reactivity unit [PRU] value of more than 234) after 1 week of dual antiplatelet treatment (DAPT), which is a marker associated with increased adverse cardiovascular events.
Exclusion Criteria
Antiplatelet treatment other than aspirin and clopidogrel or anticoagulation treatment with warfarin or dabigatran History of stroke or transient ischaemic attack Bodyweight of less than 60 kg Platelet count of less than 100 000 per μL Known bleeding diathesis Hematocrit less than 30% or more than 52% Severe liver dysfunction Renal insufficiency (creatinine clearance <30 mL/min). Pregnant women
Follow-Up
1 week and 6 months
Treatment Regimen
Carriers were given 10 mg prasugrel daily, and non-carriers and patients in the standard treatment group were given 75 mg clopidogrel daily.
Results
Primary Endpoints: 187 patients completed follow-up (91 rapid genotyping group, 96 standard treatment). 23 individuals in each group carried at least one CYP2C19*2 allele. None of the 23 carriers in the rapid genotyping group had a PRU value of more than 234 at day 7, compared with seven (30%) given standard treatment (p=0·0092). The point-of-care genetic test had a sensitivity of 100% (95% CI 92·3–100) and a specificity of 99·3% (96·3–100).
Summary
Point-of-care genetic testing after PCI can be done effectively at the bedside and treatment of identified CYP2C19*2 carriers with prasugrel can reduce high on-treatment platelet reactivity.
Implications
This study demonstrates the feasibility of genetic testing at the bedside to personalize antiplatelet therapy individually. Larger clinical trials have to be conducted to determine whether this approach can be translated into clinical benefits for patients.
Related Figures
None.