Mutational analysis clopidogrel resistance and platelet function in patients scheduled for coronary artery bypass grafting
- PMID: 23462555
- PMCID: PMC4149181
- DOI: 10.1016/j.ygeno.2013.01.005
Mutational analysis clopidogrel resistance and platelet function in patients scheduled for coronary artery bypass grafting
Abstract
Clopidogrel is an oral antiplatelet pro-drug prescribed to 40 million patients worldwide who are at risk for thrombotic events or receiving percutaneous coronary intervention (PCI). However about a fifth of patients treated with clopidogrel do not respond adequately to the drug. From a cohort of 105 patients on whom we had functional data on clopidogrel response, we used ultra-high throughput sequencing to assay mutations in CYP2C19 and ABCB1, the two genes genetically linked to respond. Testing for mutations in CYP2C19, as recommended by the FDA, only correctly predicted if a patient would respond to clopidogrel 52.4% of the time. Similarly, testing of the ABCB1 gene only correctly foretold response in 51 (48.6%) patients. These results are clinically relevant and suggest that until additional genetic factors are discovered that predict response more completely, functional assays are more appropriate for clinical use.
Copyright © 2013 Elsevier Inc. All rights reserved.
References
-
- Holmes DR, Jr, Dehmer GJ, Kaul S, Leifer D, O’Gara PT, Stein CM. ACCF/AHA clopidogrel clinical alert: approaches to the FDA “boxed warning”: a report of the American College of Cardiology Foundation Task Force on clinical expert consensus documents and the American Heart Association endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons. J Am Coll Cardiol. 2010;56(4):321–341. (Epub 2010/07/17) - PubMed
-
- Kushner FG, Hand M, Smith SC, Jr, King SB, III, Anderson JL, Antman EM, et al. Focused updates: ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction (updating the 2004 guideline and 2007 focused update) and ACC/AHA/SCAI guidelines on percutaneous coronary intervention (updating the 2005 guideline and 2007 focused update) a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2009;54(23):2205–2241. (Epub 2009/11/28) - PubMed
-
- Breet NJ, van Werkum JW, Bouman HJ, Kelder JC, Ruven HJ, Bal ET, et al. Comparison of platelet function tests in predicting clinical outcome in patients undergoing coronary stent implantation. JAMA. 2010;303(8):754–762. (Epub 2010/02/25) - PubMed
-
- Price MJ, Angiolillo DJ, Teirstein PS, Lillie E, Manoukian SV, Berger PB, et al. Platelet reactivity and cardiovascular outcomes after percutaneous coronary intervention: a time-dependent analysis of the Gauging Responsiveness with a VerifyNow P2Y12 assay: impact on Thrombosis and Safety (GRAVITAS) trial. Circulation. 2011;124(10):1132–1137. (Epub 2011/08/31) - PubMed
-
- Price MJ, Berger PB, Teirstein PS, Tanguay JF, Angiolillo DJ, Spriggs D, et al. Standard- vs high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial. JAMA. 2011;305(11):1097–1105. (Epub 2011/03/17) - PubMed
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Miscellaneous
