Does pharmacogenomic-guided selection of antiplatelet therapy reduce ischemic and bleeding events in patients hospitalized for acute coronary syndromes?
A pharmacogenomic approach to selecting antiplatelet therapy in ACS patients significantly reduces the combined risk of ischemic and bleeding events compared to standard clinical selection.
Background 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. Objectives 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. Methods 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. 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 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). Conclusions 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) Original language English Pages (from-to) 1869-1877 Journal Journal of the American College of Cardiology Volume 71 Issue number 17 Early online date 11 Mar 2018 DOIs https://doi.org/10.1016/j.jacc.2018.02.029 Publication status Published - 1 May 2018
“Selecting treatment on the basis of genetic data in addition to considerations concerning the patients' clinical characteristics may lead to a more personalized, and therefore more efficient, antiplatelet therapy, thus reducing both ischemic and bleeding risk. PHARMCLO is the first step of a new approach that will see a shift in emphasis away from trying to discover ever more potent antithrombotic drugs and toward ensuring that the right therapy is given to each individual patient.”
Notarangelo et al. (Sun,) studied this question.