Polymorphisms associated with in vitro aspirin resistance are not associated with clinical outcomes in patients with coronary artery disease who report regular aspirin use - 06/08/11
, John Horton, MS b, Svati H. Shah, MD, MHS b, c, Linda K. Shaw, MS b, L. Kristin Newby, MD, MHS bRésumé |
Background |
We hypothesized that single-nucleotide polymorphisms (SNPs) associated with heightened in vitro platelet function during aspirin exposure (which we define as “laboratory aspirin resistance”) would be associated with greater risk for death, myocardial infarction (MI) or stroke among patients with coronary artery disease regularly using aspirin.
Methods |
Duke Databank for Cardiovascular Disease patients with (n = 3,449, CATHeterization GENetics cohort) or without (n = 11,754, nongenetic cohort) banked DNA with ≥1 coronary stenosis >75% were followed up at 6 months, then annually for death, MI, or stroke occurring during periods of reported aspirin use. We evaluated associations of candidate SNPs from GNB3, PEAR1, ITGB3, VAV3, ITGA2, GPVI, PTGS1, F2R, THBS1, A2AR, and GP1BA with events during follow-up using Cox proportional hazards modeling adjusted for clinical characteristics associated with outcomes in the nongenetic cohort.
Results |
Over a median of 3.5 years, 2,762 (24%) nongenetic cohort patients and 648 (19%) CATHeterization GENetics cohort patients had the composite outcome during reported aspirin use. No candidate SNPs were significantly associated with death, MI, or stroke in either univariable or multivariable analyses. A prospective analysis demonstrated 80% to 88% power to detect a hazard ratio of ≥1.3 for minor allele carriers.
Conclusion |
Patients with angiographically significant coronary artery disease regularly using aspirin and carrying SNPs associated with laboratory aspirin resistance were not at higher risk for death, MI, or stroke. Using these SNPs to guide more aggressive antiplatelet therapy is not justified by these results. Direct extrapolation from in vitro findings to the clinical setting should be avoided.
Le texte complet de cet article est disponible en PDF.Plan
| Philip F. Binkley, MD, MPH served as guest editor for this article. |
Vol 162 - N° 1
P. 166 - juillet 2011 Retour au numéro
Article précédent
- The effect of ticagrelor versus clopidogrel on high on-treatment platelet reactivity: Combined analysis of the ONSET/OFFSET and RESPOND studies
- Kevin P. Bliden, Udaya S. Tantry, Robert F. Storey, Young-Hoon Jeong, Martin Gesheff, Cheryl Wei, Paul A. Gurbel
- Changes in reference vessel diameter in ST-segment elevation myocardial infarction after primary percutaneous coronary intervention: Implications for appropriate stent sizing
- Ecaterina Cristea, Gregg W. Stone, Roxana Mehran, Ajay J. Kirtane, Sorin J. Brener
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?