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Clinical, Angiographic, and Genetic Factors Associated With Early Coronary Stent Thrombosis
Study Questions:
What are the clinical and genetic predictors of early stent thrombosis?
Methods:
The authors performed a case-control study involving 123 patients with centrally adjudicated early stent thrombosis at 10 centers in France between January 2007 and May 2010, who were matched for gender and age with 246 stent thrombosis-free controls.
Results:
The authors evaluated 23 genetic variants related to 15 different genes. The independent predictors of early stent thrombosis were CYP2C19 metabolic status (adjusted odds ratio [OR], 1.99; 95% confidence interval [CI], 1.47-2.69), ABCB1 3435 TT genotype (adjusted OR, 2.16; 95% CI, 1.21-3.88), and ITGB3 PLA2 carriage (adjusted OR, 0.52; 95% CI, 0.28-0.95). Clinical correlates of early stent thrombosis were acuteness of percutaneous coronary intervention (PCI) (adjusted OR, 3.05; 95% CI, 1.54-6.07), complex lesions (American College of Cardiology/American Heart Association type C) (adjusted OR, 2.33; 95% CI, 1.40-3.89), left ventricular function <40% (adjusted OR, 2.25; 95% CI, 1.09-4.70), diabetes mellitus (adjusted OR, 1.82; 95% CI, 1.02-3.24), use of proton pump inhibitors (adjusted OR, 2.19; 95% CI, 1.29-3.75), and higher clopidogrel loading doses (adjusted OR, 0.73; 95% CI, 0.57-0.93). The clinical-only model and the genetic-only model had similar discrimination (area under the curve, 0.73 vs. 0.68; p = 0.34), whereas a combined clinical and genetic model was associated with a significant improvement in model discrimination (area under the curve, 0.78; 95% CI, 0.73-0.83).
Conclusions:
This case series identified three genes (CYP2C19, ABCB1, and ITGB3) and two clopidogrel-related factors (loading dose and proton pump inhibitors) that were independently associated with early stent thrombosis.
Perspective:
Stent thrombosis is a rare, but devastating complication of PCI. This study serves to define the key predictors that can be used to identify patients at high risk of this complication. The discrimination of the model is not high enough for it to be used routinely in patient care settings, but there may be a role for selective consideration of genotyping to identify patients at high risk. In general, patients at high risk for stent thrombosis (such as those with acute coronary syndrome or those undergoing PCI for complex lesions) should be routinely evaluated for use of more potent platelet inhibitors (prasugrel or ticagrelor) since the risk of early stent thrombosis is reduced by half with these agents. Further studies are warranted to identify a role for genetic testing, especially when the risk–benefit of switching to more potent agents is not so clear.
Keywords: Odds Ratio, Acute Coronary Syndrome, Platelet Aggregation Inhibitors, Thiophenes, Ticlopidine, Piperazines, Genetic Testing, Proton Pump Inhibitors, Purinergic P2Y Receptor Antagonists, Stents, Percutaneous Coronary Intervention, France, Case-Control Studies, Coronary Angiography, Ventricular Function, Confidence Intervals, Coronary Thrombosis, Genotype, United States, Diabetes Mellitus
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