Clinical, angiographic, and genetic factors associated with early coronary stent thrombosis.
BACKGROUND
Despite dual antiplatelet therapy, stent thrombosis remains a devastating and unpredictable complication of percutaneous coronary intervention (PCI).


OBJECTIVE
To perform a sequential analysis of clinical and genetic factors associated with definite early stent thrombosis.


METHODS
Case-control study conducted in 10 centers in France between January 2007 and May 2010 among 123 patients undergoing PCI who had definite early stent thrombosis and DNA samples available, matched on age and sex with 246 stent thrombosis-free controls.


METHODS
Accuracy of early stent thrombosis prediction by 23 genetic variants.


RESULTS
Among the 23 genetic variants investigated in 15 different genes, the significant determinants of early stent thrombosis were CYP2C19 metabolic status (adjusted odds ratio [OR], 1.99; 95% 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). Nongenetic independent correlates were acuteness of 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 less than 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 discriminative accuracy of the clinical-only model was similar to that of a genetic-only model (area under the curve, 0.73 [95% CI, 0.67-0.78] vs 0.68 [95% CI, 0.62-0.74], respectively; P = .34). A combined clinical and genetic model led to a statistically significant increase in the discriminatory power of the model compared with the clinical-only model (area under the curve, 0.78 [95% CI, 0.73-0.83] vs 0.73 [95% CI, 0.67-0.78]; P = .004).


CONCLUSIONS
This case-control study identified 3 genes (CYP2C19, ABCB1, and ITGB3) and 2 clopidogrel-related factors (loading dose and proton pump inhibitors) that were independently associated with early stent thrombosis. Future studies are needed to validate the prognostic accuracy of these risk factors in prospective cohorts.
Institut de Cardiologie, INSERM Unité Mixte de Recherche_S 937, Pitié-Salpêtrière Hospital, Paris, France.
Guillaume
G
Cayla
Jean-Sébastien
JS
Hulot
Stephen A
SA
O'Connor
Atul
A
Pathak
Stuart A
SA
Scott
Yves
Y
Gruel
Johanne
J
Silvain
Jean-Baptiste
JB
Vignalou
Yves
Y
Huerre
Axel
A
de la Briolle
Frédérick
F
Allanic
Farzin
F
Beygui
Olivier
O
Barthélémy
Gilles
G
Montalescot
Jean-Philippe
JP
Collet
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D016022:Case-Control Studies; D000077144:Clopidogrel; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000628:therapy; D065731:Cytochrome P-450 CYP2C19; D004247:DNA / Q000032:analysis; D005260:Female; D005602:France; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D039661:Integrin beta3 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D054328:Proton Pump Inhibitors / Q000009:adverse effects; D012307:Risk Factors; D015607:Stents / Q000009:adverse effects*; D013927:Thrombosis / Q000139:chemically induced / Q000235:genetics*; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; C061248:ITGB3 protein, human; D039661:Integrin beta3; D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors; D004247:DNA; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine