Clinical and genetic predictors of anti-platelet therapy selection in coronary artery disease patients undergoing percutaneous coronary intervention

Introduction: Our institution implemented an algorithm incorporating clinical factors and CYP2C19 genotype to guide P2Y₁₂ inhibitor selection (clopidogrel, prasugrel, or ticagrelor) in high-risk patients undergoing percutaneous coronary intervention (PCI).

Objectives: We aimed to evaluate algorithm use following its first year of implementation and identify key predictors of P2Y₁₂ inhibitor selection.

Study Design: This single-center, retrospective cohort study included 597 consecutive patients undergoing PCI from July 2012-June 2013.

Methods: Demographic and clinical characteristics, CYP2C19 genotype, and anti-platelet therapy were abstracted from the medical record. Predictors of anti-platelet therapy (clopidogrel versus either prasugrel or ticagrelor) were identified by logistic regression.

Results: Selection of clopidogrel maintenance therapy (69.8%) was more common than prasugrel (26.6%) or ticagrelor (3.5%). A CYP2C19 genotype was obtained in 433 patients (72.5%); of these, 127 (29.3%) carried 1 or 2 loss-of-function alleles (LOF carrier). Prasugrel or ticagrelor was prescribed in 101/127 (79.5%) LOF carriers. In contrast, clopidogrel was prescribed in 243/306 (79.4%) of those without a LOF allele. In addition to CYP2C19 genotype, several clinical factors were significantly associated with P2Y₁₂ inhibitor selection (see table).

Predictors of prasugrel/ticagrelor selection	Clopidogrel (n=269)	Prasugrel/Ticagrelor (n=164)	Adjusted odds ratio (95% CI)
LOF carrier	26 (9.7%)	101 (61.6%)	21.8 (12.2-41.3)
Acute myocardial infarction	98 (36.4%)	82 (50.0%)	2.10 (1.25-3.55)
Prior clopidogrel use	65 (24.1%)	14 (8.5%)	0.34 (0.15-0.71)
Age ³75	56 (20.8%)	16 (9.7%)	0.27 (0.12-0.57)
Previous stroke	23 (8.6%)	3 (1.8%)	0.14 (0.03-0.54)
End-stage renal disease	15 (5.6%)	3 (1.8%)	0.17 (0.03-0.72)

Conclusions: When available, CYP2C19 genotype is the strongest predictor of P2Y₁₂ inhibitor selection following PCI. However, acute myocardial infarction, prior clopidogrel use, contraindications to prasugrel use and end-stage renal disease are also independently associated with drug selection. Observational studies evaluating the relationship between CYP2C19 genotype and P2Y₁₂ inhibitor use will need to account for clinical factors that influence anti-platelet agent selection.