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Published on: September 22, 2020
Utility of the ACD-GENE-CLI Score in Asian Patients with Critical Limb Ischemia Undergoing Endovascular Interventions
Wei-Ting Chang1,2, Po-Sen Huang2, Li-Wei Su2
1School of Medicine and Doctoral Program of Clinical and Experimental Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University.
Insights
A new ACD-GENE-CLI score effectively predicts major adverse limb events (MALEs) in critical limb ischemia (CLI) patients on clopidogrel. This score improves upon existing methods for identifying high-risk individuals.
Area of Science:
- Vascular Medicine
- Pharmacogenomics
- Cardiovascular Research
Background:
- Critical limb ischemia (CLI) poses a significant health challenge with limited predictive tools for patient outcomes.
- The ABCD-GENE score aids in identifying cardiovascular risks related to CYP2C19 polymorphism, but its utility in CLI is unestablished.
Purpose of the Study:
- To validate a modified ACD-GENE-CLI score for predicting major adverse limb events (MALEs) in patients with CLI undergoing clopidogrel therapy.
- To assess the score's predictive performance compared to existing methods.
Main Methods:
- Prospective enrollment of 473 CLI patients receiving clopidogrel post-endovascular intervention across two centers.
- Outcomes assessed included amputation and revascularization as MALEs, with a mean follow-up of 25 months.
- Bootstrap regression analysis used to develop and validate the ACD-GENE-CLI score, incorporating age, diabetes, CKD, and CYP2C19 polymorphisms.
Main Results:
- Old age, diabetes, chronic kidney disease (CKD), and CYP2C19 polymorphisms were significantly associated with MALEs.
- The modified ACD-GENE-CLI score demonstrated superior prediction of MALEs compared to CYP2C19 deficiency alone and the conventional ABCD-GENE score (AUC 0.69 vs. 0.59 vs. 0.67).
- External validation confirmed the score's diagnostic ability, and Kaplan-Meier curves showed its utility in differentiating patients free from MALEs.
Conclusions:
- The validated ACD-GENE-CLI score effectively identifies CLI patients on clopidogrel at risk for MALEs.
- Further research is needed to broaden the application and validation of this predictive score in diverse clinical settings.
Aims:
Critical limb ischemia (CLI) is an emerging public health threat and lacks a reliable score for predicting the outcomes. The Age, Body Mass Index, Chronic Kidney Disease, Diabetes, and Genotyping (ABCD-GENE) risk score helps identify patients with coronary artery disease who have cytochrome P450 2C19 (CYP2C19) polymorphism-related drug resistance and are at risk for cardiovascular adverse events. However, its application to CLI remains unknown. In this study, we aim to validate a modified ACD-GENE-CLI score to improve the prediction of major adverse limb events (MALEs) in patients with CLI receiving clopidogrel.
Methods:
Patients with CLI receiving clopidogrel post-endovascular intervention were enrolled prospectively in two medical centers. Amputation and revascularization as MALEs were regarded as the outcomes.
Results:
A total of 473 patients were recruited, with a mean follow-up duration of 25 months. Except for obesity, old age, diabetes, chronic kidney disease (CKD), and CYP2C19 polymorphisms were significantly associated with MALEs. Using bootstrap regression analysis, we established a modified risk score (ACD-GENE-CLI) that included old age (≥ 65 years), diabetes, CKD, and CYP2C19 polymorphisms. At a cutoff value of 8, the ACD-GENE-CLI score was superior to the CYP2C19 deficiency only, and the conventional ABCD-GENE score in predicting MALEs (area under the curve: 0.69 vs. 0.59 vs. 0.67, p=0.01). The diagnostic ability of the ACD-GENE-CLI score was consistent in the external validation. Also, Kaplan-Meier curves showed that in CYP2C19 deficiency, the ABCD-GENE and ACD-GENE-CLI scores could all differentiate patients with CLI who are free from MALEs.
Conclusions:
The modified ACD-GENE-CLI score could differentiate patients with CLI receiving clopidogrel who are at risk of MALEs. Further studies are required to generalize the utility of the score.
