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 P2Y(12) 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(12) 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.