Pharmacogenomic Approach to Selecting Antiplatelet Therapy in Acute Coronary Syndromes: PHARMCLO trial

Abstract Background Clopidogrel is still frequently used in patients with acute coronary syndromes (ACS), but its efficacy is hampered by interpatient response variability, due to genetic polymorphisms associated with clopidogrel metabolism. Objective To evaluate whether selecting antiplatelet therapy (clopidogrel, prasugrel or ticagrelor) on the basis of a patient’s genetic and clinical characteristics leads to better clinical outcomes in comparison with the standard of care, which bases the selection on clinical characteristics alone Methods Patients hospitalised for ACS were randomly assigned to standard of care or pharmacogenomic arm, which included the genotyping of ABCB1, CYP2C19*2, CYP2C19*17 using an ST Q3 system that provide the data within 70 minutes at each patient’s bedside. The patients were followed up for 12 ± 1 months for the primary composite endpoint of cardiovascular death and the first occurrence of non-fatal myocardial infarction, non-fatal stroke andBARC 3 to 5-defined major bleeding. Results After enrolling 888 patients, the study was prematurely stopped. Clopidogrel was used more frequently in the standard of care arm (50.7% vs 43.3%), ticagrelor in the pharmacogenomic arm (42.6% vs 32.7%; P=0.02), and prasugrel was equally used in both arms. The primary endpoint occurred in 71 patients (15.9%) in thepharmacogenomicarm and in 114 (25.9%) in the standard of care arm (hazard ratio 0.58; 95% confidence interval [CI] 0.43 to 0.78; P Conclusion A personalised approach to selecting antiplatelet therapy for ACS patients may reduce ischemic and bleeding events (PHARMCLO - NCT03347435).