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Published on: November 8, 2024
Derivation of a Novel Scoring System Predicting High Platelet Reactivity on Prasugrel in Patients with Coronary
Yuichi Saito1, Takeshi Nishi1,2, Shinichi Wakabayashi1,3
1Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine.
Insights
A new HHD-GENE score predicts high platelet reactivity (HPR) in patients taking prasugrel. This score uses hypertension, diabetes, hemodialysis, and CYP2C19 gene variants to identify at-risk individuals.
Area of Science:
- Cardiology
- Pharmacogenomics
- Thrombosis Research
Background:
- High platelet reactivity (HPR) increases thrombotic event risk post-percutaneous coronary intervention.
- While HPR on clopidogrel is studied, HPR on prasugrel remains less understood.
Purpose of the Study:
- To investigate factors associated with HPR in patients treated with prasugrel.
- To develop and validate a predictive model for HPR on prasugrel.
Main Methods:
- Pooled analysis of four prospective studies involving 180 patients.
- Platelet reactivity measured by VerifyNow assay; CYP2C19 genotyping performed.
- Multivariable analysis identified risk factors; HHD-GENE score developed.
Main Results:
- 28% of patients exhibited HPR on prasugrel.
- Hypertension, diabetes, hemodialysis, and CYP2C19 loss-of-function (LOF) alleles were significant predictors.
- The HHD-GENE score (AUC 0.74) effectively predicted HPR, with a score ≥ 5 indicating significantly higher risk.
Conclusions:
- The HHD-GENE score, incorporating hypertension, diabetes, hemodialysis, and CYP2C19 LOF alleles, may identify patients at high risk for HPR on prasugrel.
- Further external validation is required to establish the clinical utility of this scoring system.
Aims:
High platelet reactivity (HPR) has been associated with an increased risk of thrombotic events in patients undergoing percutaneous coronary intervention. HPR has been well examined in patients treated with clopidogrel; however, HPR on prasugrel is poorly investigated.
Methods:
Four prospective studies were pooled, in which platelet reactivity on prasugrel was measured using VerifyNow assay; genotyping of CYP2C19 was also performed. Factors associated with HPR on prasugrel were identified using multivariable analysis to develop a risk prediction model.
Results:
In total, 180 patients were examined in this study, of whom 51 (28%) had HPR on prasugrel. The multivariable analysis indicated that hypertension, diabetes, hemodialysis, and the number of CYP2C19 loss-of-function (LOF) alleles are significant factors for HPR on prasugrel. These four factors were then incorporated to develop the HHD-GENE score. The receiver operating characteristic curve analysis showed that the HHD-GENE score predicted HPR on prasugrel (area under the curve (AUC) 0.74, best cutoff value 5, p＜0.001). With the best cutoff value, patients with the HHD-GENE score ≥ 5 had a significantly increased risk of HPR on prasugrel than their counterpart (50% vs. 18%, p＜0.001).
Conclusions:
The HHD-GENE score consisting of hypertension, diabetes, hemodialysis, and CYP2C19 LOF alleles may be useful in identifying patients on prasugrel who are at high risk for HPR. External validation is needed to define the clinical utility of this novel scoring system.
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