Abstract 12855: Added Value of Pharmacogenetic Factors to a Clinical Risk Score for Prediction f oThrombotic Events After ST-Segment Elevation Myocardial Infarction
Introduction: Several single nucleotide polymorphisms (SNPs), related to antiplatelet drug efficacy, are known to be associated with adverse events during antiplatelet therapy. However, their added value to clinical risk prediction models is uncertain, limiting their possible clinical application. The objective was to determine whether SNPs had added value to a clinical risk score for the prediction of thrombotic events after STEMI.
Methods: In total, 1,259 patients (mean age 60.4 ± 11.7 years, 77% male) presenting with STEMI, treated with primary PCI and dual antiplatelet therapy with aspirin and clopidogrel were included. A risk score was constructed using multivariate Cox regression, identifying age, diabetes mellitus, 3-vessel disease, cardiogenic shock during PCI, TIMI flow, peak troponin T and β-blocker treatment as relevant factors for the prediction of thrombotic events (cardiac death, recurrent myocardial infarction or stent thrombosis), during the first year after STEMI. This score was evaluated with and without the SNPs COX1 -842A>G and CYP2C19*2, both previously associated with antiplatelet response. Improvement of the model was determined by change in the c-index of the ROC curve and net reclassification improvement (NRI).
Results: During follow-up, 62 patients suffered from a thrombotic event. Both SNPs were strongly associated with the combined endpoint, with a HR of 2.3 (95% CI 1.4-3.9), P=0.001 for COX1 and a HR of 2.3 (1.5-3.4), P<0.001 for CYP2C19. The clinical risk score classified patients into 4 categories and addition of the SNPs reclassified 10% of all patients. The genetic score was significantly associated with of thrombotic events, HR 4.1 (2.9-5.6), P<0.001. Compared to the clinical score, the SNPs improved the c-index from 0.7 to 0.8, P=0.07 and significantly increased the NRI to 13%, P=0.03.
Conclusion: Two SNPs related to antiplatelet drug efficacy improved the thrombotic risk prediction of patients after STEMI, compared to a score consisting of only clinical factors. Although the effect size and clinical usefulness of most SNPs is limited, this study provides evidence that, for specific endpoints, genetic data could improve clinical risk assessment.
- © 2012 by American Heart Association, Inc.