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 P2Y₁₂ 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 P2Y₁₂ 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 P2Y₁₂ 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 P2Y₁₂ inhibitors, which needs to be confirmed in prospective investigations. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique Identifier: NCT01742117.

Keywords: antiplatelet therapy; genetic testing; ischemia; percutaneous coronary intervention.

Figure 1. Study flowchart.

A total of 4714 patients randomized in the TAILOR‐PCI trial had complete data for the calculation of the ABCD‐GENE score. Of them 1014 had a high (≥10) ABCD‐GENE score and 3700 (<10) had a low ABCD‐GENE score. A total of 3883 patients were discharged on clopidogrel (613 and 3270 with high and low ABCD‐GENE scores, respectively). ABCD‐GENE indicates Age, Body Mass Index, Chronic Kidney Disease, Diabetes, and Genotyping.

Figure 2. Incidence of death, myocardial infarction, or stroke in patients discharged on clopidogrel with high ABCD‐GENE score ≥10 or <10.

ABCD‐GENE indicates Age, Body Mass Index, Chronic Kidney Disease, Diabetes, and Genotyping; CVA, cerebrovascular accidents; HR, hazard ratio; and MI, myocardial infarction. The shaded areas represent 95% CIs for the survival curves.

Figure 3. Summary of results.

At 1 year, the risk of death, myocardial infarction, or stroke was significantly predicted by the ABCD‐GENE score (high versus low) but not by the presence of 1 or 2 loss of function alleles. ABCD‐GENE indicates Age, Body Mass Index, Chronic Kidney Disease, Diabetes, and Genotyping; BMI, body mass index; CKD, chronic kidney disease; HR, hazard ratio, LOF, loss of function; MI, myocardial infarction; and PCI, percutaneous coronary intervention.

Figure 4. Incidence of death, myocardial infarction, or stroke in patients who received genotype‐guided or conventional therapy by ABCD‐GENE score groups.

At 1 year, the risk of death, myocardial infarction, or stroke was not significantly reduced in the genotype‐guided therapy arm compared with the conventional therapy in both the high and low ABCD‐GENE score g subgroups. ABCG‐GENE denotes Age, Body Mass Index, Chronic Kidenye Disease, Diabetes, and Genotyping; CVA, cerebrovascular accidents; HR, hazard ratio; and MI, myocardial infarction.