Background: The effectiveness of genotype-guided selection of oral P2Y12 inhibitors for patients undergoing primary percutaneous coronary intervention (PCI) remains uncertain. This study investigates whether such a strategy improves outcomes compared to standard treatment.
Methods: A randomized, open-label, assessor-blinded trial was conducted involving patients undergoing primary PCI with stent implantation. Participants were assigned in a 1:1 ratio to either a CYP2C19 genotype-guided P2Y12 inhibitor selection group or a standard-treatment group for 12 months. The genotype-guided group received ticagrelor or prasugrel if they carried CYP2C19*2 or CYP2C19*3 loss-of-function alleles, and clopidogrel if they were noncarriers. The standard-treatment group received either ticagrelor or prasugrel.
The primary outcomes assessed at 12 months were: 1) Net adverse clinical events (NACE), defined as death from any cause, myocardial infarction, definite stent thrombosis, stroke, or major bleeding (per Platelet Inhibition and Patient Outcomes [PLATO] criteria); this was tested for noninferiority with a margin of 2 percentage points. 2) PLATO major or minor bleeding events.
Results: The primary analysis included 2488 patients: 1242 in the genotype-guided group and 1246 in the standard-treatment group. The primary combined outcome (NACE) occurred in 63 patients (5.1%) in the genotype-guided group and in 73 patients (5.9%) in the standard-treatment group. The absolute difference was -0.7 percentage points (95% confidence interval [CI], -2.0 to 0.7; P<0.001 for noninferiority).
Regarding the primary bleeding outcome, 122 patients (9.8%) in the genotype-guided group and 156 patients (12.5%) in the standard-treatment group experienced PLATO major or minor bleeding events (hazard ratio, 0.78; 95% CI, 0.61 to 0.98; P = 0.04).
Conclusions: In patients undergoing primary PCI, a CYP2C19 genotype-guided strategy for oral P2Y12 inhibitor selection was noninferior to standard treatment with ticagrelor or prasugrel regarding thrombotic events. This strategy also resulted in a significantly lower incidence of bleeding events.
This study suggests that utilizing a patient’s CYP2C19 genotype to guide P2Y12 inhibitor selection could improve outcomes following primary PCI.
