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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Jean-Sebastien
Hulot
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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.