NEW ORLEANS, LA—The debate over the use of pharmacogenomic- or pharmacodynamic-tailored antiplatelet therapy continues to be a subject of interest at ACC.11, the American College of Cardiology’s 60th Annual Scientific Session. Deepak Bhatt, MD, MPH, FACC from the Cleveland Clinic and Matthew Price, MD from Scripps Clinic in San Diego presented evidence supporting the use of pharmacogenomic assessment to guide the use of clopidogrel (Plavix) antiplatelet therapy.
Despite the proven efficacy of clopidogrel in the reduction of CV events, ischemic events continue to occur with an estimated event rate of 8.8% one year following percutaneous coronary intervention (PCI). This can be attributed to the substantial variability in the antiplatelet effect of clopidogrel due to the CYP2C19 genotype and other polymorphisms. Dr. Bhatt presented data from the PLATO study demonstrating that carriers of the CYP2C19*2 gene are poor responders to clopidogrel therapy and experience a greater event rate (12.1%) of death, myocardial infarction (MI), stroke, and urgent revascularization compared with 8% of noncarriers (P=0.01). Additionally, time to first CV event was worse in CYP2C19*2 carriers as compared with noncarriers (HR=3.69 [1.69-8.05]; P=0.0005).
The GRAVITAS study, presented by Dr. Price, was designed to determine if doubling the standard dose of clopidogrel (75mg/day) would overcome poor-responsiveness. Poor responders were defined as patients with high residual on-treatment platelet activity, established as ≥230 P2Y12 reactivity units (PRU). PRU was measured with the VerifyNowP2Y12 assay. Compared with standard-dose therapy, high-dose clopidogrel (150mg/day) achieved a modest reduction in on-treatment platelet reactivity. However, in patients with high-reactivity after PCI, 6-months of clopidogrel 150mg did not reduce the rate of CV death, non-fatal MI, or stent thrombosis compared with clopidogrel 75mg (2.3% vs. 2.3%; HR=1.01 [0.58–1.78]; P=0.98). Though clinical benefit was not observed in this trial, Dr. Price states that the results suggest that further studies should assess if larger doses may be needed for adequate platelet inhibition.