Background Studies have demonstrated increased risk of major atherothrombotic events in
CYP2C19 loss-of-function (LOF) variant carriers versus non-carriers treated with
clopidogrel after
percutaneous coronary intervention (PCI). We sought to evaluate real-world outcomes with the clinical implementation of CYP2C19-guided antiplatelet
therapy after PCI. Methods and Results Data from 9 medical centers where genotyping was performed in the setting of PCI were included. Alternative
therapy with
prasugrel or
ticagrelor was recommended for patients with a
CYP2C19 LOF variant. The primary outcome was the composite of major atherothrombotic events (all-cause death,
myocardial infarction,
ischemic stroke,
stent thrombosis, or hospitalization for
unstable angina) within 12 months following PCI. Moderate or severe/life-threatening
bleeding within 12 months was a secondary outcome. Among 3342 patients, 1032 (31%) were LOF carriers, of whom 571/1032 (55%) were treated with alternative
therapy. In LOF carriers, the rate of major atherothrombotic events was lower in patients treated with alternative
therapy versus
clopidogrel (adjusted HR, 0.56; 95% CI 0.39-0.82). In those without a LOF allele, no difference was observed (adjusted HR, 1.07; 95% CI 0.71-1.60). There was no difference in
bleeding with alternative
therapy versus
clopidogrel in either LOF carriers or those without a LOF allele. Conclusions Real-world data demonstrate lower atherothrombotic risk in
CYP2C19 LOF carriers treated with alternative
therapy versus
clopidogrel and similar risk in those without a LOF allele treated with
clopidogrel or alternative
therapy. These data suggest that PCI patients treated with
clopidogrel should undergo genotyping so that
CYP2C19 LOF carriers can be identified and treated with alternative
therapy.