Intensive care medicine

Engineering

Prasugrel

Acute coronary syndrome

Clinical trial

Metabolism

Cardiology

Cytochrome P450

Pharmacogenomics

Mechanical engineering

CYP2C19

Stroke (engine)

Ticagrelor

Myocardial infarction

Internal medicine

Clinical endpoint

Pharmacology

Confidence interval

Hazard ratio

Medicine

Clopidogrel

Journal of the American College of Cardiology

Although clopidogrel is still frequently used in patients with acute coronary syndromes (ACS), its efficacy is hampered by interpatient response variability caused by genetic polymorphisms associated with clopidogrel's metabolism.The goal of this study was 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 compared with the standard of care, which bases the selection on clinical characteristics alone.Patients hospitalized for ACS were randomly assigned to standard of care or the pharmacogenomic arm, which included the genotyping of ABCB1, CYP2C19*2, and CYP2C19*17 using an ST Q3 system that provides data within 70 min at each patient's bedside. The patients were followed up for 12 ± 1 month for the primary composite endpoint of cardiovascular death and the first occurrence of nonfatal myocardial infarction, nonfatal stroke, and major bleeding defined according to Bleeding Academic Research Consortium type 3 to 5 criteria.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 the pharmacogenomic arm and in 114 (25.9%) in the standard-of-care arm (hazard ratio: 0.58; 95% confidence interval: 0.43 to 0.78; p < 0.001).A personalized approach to selecting antiplatelet therapy for patients with ACS may reduce ischemic and bleeding events. (Pharmacogenetics of Clopidogrel in Patients With Acute Coronary Syndromes [PHARMCLO]; NCT03347435).

Pharmacogenomic Approach to Selecting Antiplatelet Therapy in Patients With Acute Coronary Syndromes