• Cardiology Clinical Trials
• Coronary Artery Disease
• Cardiology Genomics
• Nursing

Previous studies suggest that CYP2C19 loss-of-function alleles affect clopidogrel metabolism and are associated with major adverse cardiac events (MACE) and stent thrombosis. CYP2C19*2 accounts for 95% of CYP2C19 loss-of-function alleles and occurs in up to 25% of Caucasian populations and 40% of Asian populations.

Currently, most genetic testing is done in central laboratories, with a turnaround time of 2 to 7 days. This delay has prevented the prospective evaluation of genetic testing in percutaneous coronary intervention (PCI) studies. The University of Ottawa Heart Institute, in collaboration with Spartan Biosciences, created the first point-of-care (POC) genetic test. After 1 hour, nurses were able to determine a patient's CYP2C19*2 carrier status and whether the patient was heterozygous or homozygous by utilizing the new technology.

The primary objective of the Reassessment of Antiplatelet Therapy using an Individualized Strategy Based on Genetic Evaluation (NCT01184300; RAPID GENE) study, presented by Derek So, MD, University of Ottawa Heart Institute, Ottawa, Ontario, Canada, was to evaluate the feasibility and test characteristics of a nurse-operated POC genetic test to determine CYP2C19*2 carrier status.

PCI patients with non-ST elevation acute coronary syndrome (ACS) or stable coronary artery disease (CAD) were pretreated with a minimum of 600 mg clopidogrel. Following baseline platelet function testing, the patients were randomized 1:1 to rapid genotyping (RG; n=102) using the new POC technology or to no POC testing and standard therapy (ST; n=98) with clopidogrel 75 mg daily. In the RG group, CYP2C19*2 carriers were treated with prasugrel 10 mg daily, and noncarriers were treated with clopidogrel 75 mg daily. At 1 week, all patients underwent platelet function testing and DNA sequencing. Patients in the ST arm also underwent POC rapid genotyping after 1 week.

The primary endpoint was the proportion of CYP2C19*2 carriers with a P₂Y12 reaction unit (PRU) >234 (consistent with high on-treatment platelet reactivity) after 1 week of dual antiplatelet therapy.

In the RG arm, POC genotyping identified 25.3% (n=23) of patients as CYP2C19*2 carriers, with 20.9% heterozygous and 4.4% homozygous. In the ST group after 1 week, POC genotyping identified a similar proportion of patients as CYP2C19*2 carriers (24.0%; n=23), with 20.8% heterozygous and 3.1% homozygous. Compared with direct DNA sequencing, POC genotyping had a sensitivity of 100%, specificity of 99.4%, and a conclusive rate of 93.6%.

The proportion of CYP2C19*2 carriers with high on-treatment platelet reactivity (PRU >234) was significantly lower in the RG group (prasugrel-treated) compared with the ST group (clopidogrel-treated; 0% vs 30.4%; p=0.009). CYP2C19*2 carriers who were treated with prasugrel as compared with clopidogrel had a significantly lower PRU at 7 days (75.6 vs 207.3 PRU; p<0.001) and greater platelet inhibition after 7 days (73.3 vs 27.0 PRU; p<0.001), demonstrating the superior antiplatelet efficacy of prasugrel in this population. No MACE occurred in either group at 7 and 30 days.

POC genetic testing at the bedside, performed by nurses, is feasible and can accurately identify CYP2C19*2 carriers. This novel, rapid genetic test facilitates rapid personalization of antiplatelet therapy. Administration of prasugrel to CYP2C19*2 carriers decreased the rate of high on-treatment platelet reactivity relative to standard therapy with clopidogrel. These findings represent the validation and proof-of-concept of the first POC genetic test in clinical medicine. The results of the RAPID GENE trial will hopefully lead to larger-scale studies that can establish the role of pharmacogenomic tailored antiplatelet therapy after PCI.

• © 2011 MD Conference Express