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Genetic, drug-related factors linked to early stent thrombosis
Cayla G. JAMA. 2011;306:1765-1774.
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Three genes and two clopidogrel-related factors were independently linked to early stent thrombosis in a cohort of 123 patients in France, according to recent results.
Jean-Sébastien Hulot, MD, PhD, associate professor of medicine at Mount Sinai School of Medicine, N.Y., and colleagues identified eligible participants as those who underwent percutaneous coronary intervention, had definite early stent thrombosis and had DNA samples available for analysis. Findings from the study drug cohort were compared with those from 246 age- and sex-matched controls who did not have stent thrombosis.
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The primary outcome was accuracy of early stent thrombosis prediction by 23 genetic variants. The researchers investigated 15 different genes.
Early stent thrombosis was significantly linked to CYP2C19 metabolic status (OR=1.99; 95% CI, 1.47-2.69), ABCB1 3435 TT genotype (OR=2.16; 95% CI, 1.21-3.88) and ITGB3 PLA2 carriage (OR=0.52; 95% CI, 0.28-0.95).
“Adding the genetic information to classical risk factors helped identify a subgroup of patients with an eightfold higher risk for developing stent thrombosis under dual antiplatelet therapy,” Hulot told Cardiology Today. “Beyond the prediction of stent thrombosis, this study illustrates how a ‘clinico-genomics’ model could help in the assessment of CV risk.”
Several non-genetic independent factors also were associated with early stent thrombosis, including:
- Acuteness of PCI (OR=3.05; 95% CI, 1.54-6.07);
- Complex lesions (ACC/AHA type C; OR=2.33; 95% CI, 1.40-3.89);
- Left ventricular function <40% (OR=2.25; 95% CI, 1.09-4.70);
- Diabetes (OR=1.82; 95% CI, 1.02-3.24);
- Use of proton pump inhibitors (OR=2.19; 95% CI, 1.29-3.75); and
- Higher loading doses of clopidogrel (OR=0.73; 95% CI, 0.57-0.93).
The discriminative accuracy of the clinical-only model was area under the curve (AUC) of 0.73 (95% CI, 0.67-0.78) vs. an AUC of 0.68 (95% CI, 0.62-0.74) in the genetic-only model (P=.34).
A statistically significant increase in discriminatory power was observed in a combined clinical and genetic model compared with a clinical-only model (AUC=0.78; 95% CI, 0.73-0.83 for the combined model vs. AUC=0.73; 95% CI, 0.67-0.78 for the clinical-only model).
“Genetic testing has been criticized because of its low predictive value and its potential redundancy with other markers, including clinical characteristics,” Hulot said. “In our study, the genetic variables were as predictive as the clinical and procedural variables. In other words, the invisible part of the iceberg is as big as its visible part. As a consequence, the combination of genetic and clinical risk factors allows a better discrimination of patients at risk as compared with a clinical-only or a genetic-only strategy.”
The researchers aimed to perform a sequential analysis of clinical and genetic factors linked to definite early stent thrombosis in patients from 10 centers in France. The trial was conducted between January 2007 and May 2010.
Disclosure: Dr. Hulot reports receiving research grant support from Fondation de France, INSERM, Federation Francaise de Cardiologie, Biotronik and Medco Research Institute; consulting fees from Biotronik and Medco Health Solutions; and lecture fees from Sanofi-Aventis, Daiichi Sankyo and Eli Lilly.
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