Impact of the ABCD‐GENE Score on Clopidogrel Clinical Effectiveness after PCI: A Multi‐Site, Real‐World Investigation

Abstract

The Age, Body mass index, Chronic kidney disease, Diabetes mellitus, and CYP2C19 GENEtic variants (ABCD‐GENE) score was developed to identify patients at risk for diminished antiplatelet effects with clopidogrel after percutaneous coronary intervention (PCI). The objective of this study was to validate the ability of the ABCD‐GENE score to predict the risk for atherothrombotic events in a diverse, real‐world population of clopidogrel‐treated patients who underwent PCI and received clinical CYP2C19 genotyping to guide antiplatelet therapy. A total of 2,341 adult patients who underwent PCI, were genotyped for CYP2C19, and received treatment with clopidogrel across four institutions were included (mean age 64 ± 12 years, 35% women, and 20% Black). The primary outcome was major atherothrombotic events, defined as the composite of all‐cause death, myocardial infarction, ischemic stroke, stent thrombosis, or revascularization for unstable angina within 12 months following PCI. Major adverse cardiovascular events (MACE), defined as the composite of cardiovascular death, myocardial infarction, ischemic stroke, or stent thrombosis, was assessed as the secondary outcome. Outcomes were compared between patients with an ABCD‐GENE score ≥ 10 vs. < 10. The risk of major atherothrombotic events was higher in patients with an ABCD‐GENE score ≥ 10 (n = 505) vs. < 10 (n = 1,836; 24.6 vs. 14.7 events per 100 patient‐years, adjusted hazard ratio (HR) 1.66, 95% confidence interval (CI), 1.23–2.25, P < 0.001). The risk for MACE was also higher among patients with a score ≥ 10 vs. < 10 (16.7 vs. 10.1 events per 100 patient‐years, adjusted HR 1.59, 95% CI 1.11–2.30, P = 0.013). Our diverse, real‐world data demonstrate diminished clopidogrel effectiveness in post‐PCI patients with an ABCD‐GENE score ≥ 10.

Evaluation of race and ethnicity disparities in outcome studies of CYP2C19 genotype-guided antiplatelet therapy

“…In order to rigorously and equitably evaluate clinical utility, additional outcome studies of genotype-guided antiplatelet therapy conducted in diverse real-world ACS/PCI and neurovascular disease patient populations that target enrollment of key underrepresented groups should be pursued. Additional studies evaluating the clinical utility of risk stratification tools that integrate clinical and genetic factors, such as the ABCD-GENE score, in diverse patient population are warranted ( 89 , 90 ).…”

Pharmacogenetics of P2Y12 receptor inhibitors

“…6 These include advanced age, 84 increased body mass index, [85][86][87] chronic kidney disease, 88 and diabetes mellitus 89,90 ; all have been associated with The score has been examined for its ability to predict outcomes with clopidogrel treatment after PCI in several studies, including in the real-world IGNITE cohort described above. [91][92][93][94] In each case, a score ≥ 10 was associated with an increased risk of MACE versus a score <10 in clopidogrel-treated patients. The score has also been evaluated in CHANCE trial.…”

“…The score was developed based on platelet function data, with each variable included being individually associated with high on‐treatment platelet reactivity. The score has been examined for its ability to predict outcomes with clopidogrel treatment after PCI in several studies, including in the real‐world IGNITE cohort described above 91‐94 . In each case, a score ≥ 10 was associated with an increased risk of MACE versus a score <10 in clopidogrel‐treated patients.…”