Genotype- and phenotype-directed personalization of antiplatelet treatment in patients with non-ST elevation acute coronary syndromes undergoing coronary stenting

Background and Objectives: We evaluated the effectiveness of genotype- and phenotype-directed individualization of P2Y₁₂ inhibitors to decrease high on-treatment platelet reactivity (HOPR). Subjects and Methods: Sixty-five patients undergoing percutaneous coronary intervention for non-ST elevation acute coronary syndromes were randomly assigned to genotype- or phenotype-directed treatment. All patients were screened for CYP2C19*2, *3, or *17 alleles by using the Verigene CLO assay (Nanosphere, Northbrook, IL USA). The P2Y_I2 reaction unit (PRU) was measured using the VerifyNow P2Y12 assay (Accumetrics, San Diego, CA, USA). 21 CYP2C19 *2 or *3 carriers (65.6%) and 11 patients with HOPR (33.3%), defined as a PRU value ≥230, were given 90 mg ticagrelor twice daily; non-carriers and patients without HOPR were given 75 mg Clopidogrel daily. The primary endpoint was the percentage of patients with HOPR after 30 days of treatment. Results: PRU decreased following both genotype- and phenotype-directed therapies (242±83 vs. 109±90, p<0.001 in the genotype-directed group; 216±74 vs. 109±90, p=0.001 in the phenotype-directed group). Five subjects (16.2%) in the genotype-directed group and one (3.3%) in the phenotype-directed group had HOPR at day 30 (p=0.086). All patients with HOPR at the baseline who received ticagrelor had a PRU value of <230 after 30 days of treatment. Conversely, clopidogrel did not lower the number of patients with HOPR at the baseline. Conclusion: Tailored antiplatelet therapy according to point-of-care genetic and phenotypic testing may be effective in decreasing HOPR after 30 days.