Effect of CYP2C19 genotype on outcomes of treatment with ticagrelor versus clopidogrel in acute coronary syndrome patients with diabetes mellitus: A analysis in a large-scale, real-world study.

Objective: This study evaluates the impact of CYP2C19 genotype on the outcomes of ticagrelor versus clopidogrel-based dual antiplatelet therapy (DAPT) in acute coronary syndrome (ACS) patients with diabetes mellitus (DM).

Methods: A total of 10,376 ACS patients with DM treated with ticagrelor (N = 2931) or clopidogrel (N = 7445) following percutaneous coronary intervention (PCI) were included. Patients were categorized by CYP2C19 genotype into non-carriers (N = 4326) and loss-of-function (LOF) allele carriers (N = 6050). The primary outcome was a composite of fatal or irreversible ischemic and bleeding events at 12 months, including cardiac death, myocardial infarction, stroke, and Bleeding Academic Research Consortium (BARC) types 3 or 5 bleeding.

Results: Among patients with normal CYP2C19 enzyme function, ticagrelor use compared with clopidogrel was not associated with a reduction of fatal or irreversible ischemic and bleeding events (hazard ratio [HR], 1.04; 95 % confidence interval [CI], 0.70 to 1.55; p = 0.85) with excessive risk of BARC type 2 bleeding (HR, 1.72; 95 % CI, 1.13 to 2.63; p = 0.01). Among patients carried CYP2C19 loss-of-function (LOF) alleles, those treated with ticagrelor were associated with a lower risk of fatal or irreversible ischemic and bleeding events (HR, 0.69; 95 % CI, 0.50 to 0.95; p = 0.02) and all-cause death (HR, 0.58; 95 % CI, 0.34 to 0.97; p = 0.04), albeit with a higher incidence of BARC type 2 bleeding (HR, 1.86; 95 % CI, 1.38 to 2.51; p = 0.0001).

Conclusions: The CYP2C19 genotype could be used to identify potential patients who would derive benefit from the ticagrelor-based antiplatelet strategy. Further research is warranted to trade off in bleeding complications from potent P2Y12 inhibitors.