ABCD‐GENE Score and Clinical Outcomes Following Percutaneous Coronary Intervention: Insights from the TAILOR‐PCI Trial

Abstract

Background In TAILOR‐PCI, genotype‐guided selection of P2Y 12 inhibitors after percutaneous coronary intervention did not significantly reduce the risk of ischemic events at 12 months. The Age, Body Mass Index, Chronic Kidney Disease, Diabetes, and Genotyping (ABCD‐GENE) score identifies patients with high platelet reactivity on clopidogrel at increased risk of ischemic events. The aim of this study was to investigate the value of the ABCD‐GENE score for tailoring P2Y 12 inhibitor selection after percutaneous coronary intervention. Methods and Results In a post hoc analysis of the TAILOR‐PCI, outcomes were analyzed by ABCD‐GENE score and allocation to genotype‐guided or conventional P2Y 12 inhibitor selection. Primary (death, myocardial infarction, or stroke) and secondary (cardiovascular death, myocardial infarction, stroke, stent thrombosis, or severe recurrent ischemia) outcomes were assessed. Among 3883 patients discharged on clopidogrel in the genotype‐guided and conventional therapy groups, 15.8% and 84.2% had high (≥10 points) or low (<10) ABCD‐GENE scores, respectively. At 12 months, both the primary (5.2% versus 2.6%, P <0.001) and secondary outcomes (7.7% versus 4.6%, P =0.001) were significantly increased in patients with high ABCD‐GENE score. Among 4714 patients allocated to genotype‐guided or conventional therapy, the former did not significantly reduce the 12‐month risk of the primary and secondary outcomes in both the high and low ABCD‐GENE score groups (p interaction =0.48 and 0.27, respectively). Conclusions Among patients with percutaneous coronary intervention on clopidogrel, the ABCD‐GENE score was helpful in identifying those at higher risk. The ABCD‐GENE score may potentially enhance the precision of tailored selection of P2Y 12 inhibitors, which needs to be confirmed in prospective investigations. Clinical Trial Registration URL: http://www.clinicaltrials.gov . Unique Identifier: NCT01742117.

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

“…28,38 Most recently, the predictive value of the ABCD-GENE score in identifying patients at increased risk of ischemic events was shown in a post hoc analysis of data from predominately White or Asian participants in a clinical trial of genotype-guided therapy after PCI. 27 Similar to findings from European registries and post hoc analysis of clinical trial data, we found that the risk of major atherothrombotic events and MACE was ~ 1.6-fold higher in clopidogrel-treated patients who underwent PCI with an ABCD-GENE score ≥ 10 compared with those with a score < 10 in a diverse, real-world clinical setting. Moreover, the increased risk for MACE observed herein among those with an ABCD-GENE score ≥ 10 vs. < 10 (adjusted HR 1.59, 95% CI 1.11-2.30) was comparable to the risk for MACE reported in the FAST-MI registry (adjusted HR 1.48, 95% CI 1.16-1.90).…”

“…The score was further evaluated in Asian patients for its association with HPR with clopidogrel after PCI and its association with recurrent stroke with clopidogrel plus aspirin vs. aspirin alone following minor stroke or transient ischemic attack 28,38 . Most recently, the predictive value of the ABCD‐GENE score in identifying patients at increased risk of ischemic events was shown in a post hoc analysis of data from predominately White or Asian participants in a clinical trial of genotype‐guided therapy after PCI 27 . Similar to findings from European registries and post hoc analysis of clinical trial data, we found that the risk of major atherothrombotic events and MACE was ~ 1.6‐fold higher in clopidogrel‐treated patients who underwent PCI with an ABCD‐GENE score ≥ 10 compared with those with a score < 10 in a diverse, real‐world clinical setting.…”

“…24,26 The ABCD-GENE score was subsequently shown to identify patients at increased risk of MACE in post hoc analyses of predominately European and Asian clinical trial participants receiving clopidogrel after PCI or ischemic stroke. 27,28 However, validation of the ABCD-GENE score in a more diverse cohort of patients undergoing PCI in realworld clinical practice is necessary to assess the generalizability and potential clinical utility of this risk stratification tool. In addition, only the CYP2C19*2 no function allele was considered in the evaluation of the score.…”

“…The score was evaluated in two clopidogrel‐treated European cohorts, with a score ≥ 10 predicting both HPR following elective PCI 25 and increased risk for major adverse cardiovascular events (MACE) among patients with myocardial infarction (MI), most of whom underwent PCI 24,26 . The ABCD‐GENE score was subsequently shown to identify patients at increased risk of MACE in post hoc analyses of predominately European and Asian clinical trial participants receiving clopidogrel after PCI or ischemic stroke 27,28 . However, validation of the ABCD‐GENE score in a more diverse cohort of patients undergoing PCI in real‐world clinical practice is necessary to assess the generalizability and potential clinical utility of this risk stratification tool.…”

De-escalation of antiplatelet therapy in acute coronary syndromes: Why, how and when?

“…Genetic testing for CYP2C19 alleles has the key advantage that the genetic makeup of an individual remains unvaried and does not require a patient to be on treatment with clopidogrel, but presents the disadvantage that CYP2C19 genotypes represents only one of the factors contributing to clopidogrel response. Integrating genetic data with clinical variables (age, body mass index, chronic kidney disease, and diabetes mellitus) such as in the ABCD-GENE score can enhance the accuracy in identifying individual with impaired clopidogrel response (i.e., HPR status) ( 22 , 41 , 42 ). Importantly, the implementation of these tools is associated with reduced costs due to the larger use of generic P2Y 12 inhibitor formulations and reduced clinical events and hospitalizations ( 43 ).…”