JAMA -- Clopidogrel and the Reduced-Function CYP2C19 Genetic Variant: A Limited Piece of the Overall Therapeutic Puzzle, October 27, 2010, Fuster and Sweeny 304 (16): 1839

Clopidogrel and the Reduced-Function CYP2C19 Genetic Variant

A Limited Piece of the Overall Therapeutic Puzzle

Valentin Fuster, MD, PhD; Joseph M. Sweeny, MD

JAMA. 2010;304(16):1839-1840. doi:10.1001/jama.2010.1566


Since this article does not have an abstract, we have provided the first 150 words of the full text and any section headings.


Effective platelet inhibition has become a cornerstone in the management of patients with acute coronary syndrome (ACS). The addition of clopidogrel to aspirin has provided significant reductions in major cardiovascular events in patients with ACS in general, and particularly among those treated invasively by percutaneous coronary intervention (PCI).1 Yet studies have demonstrated that the therapeutic response of clopidogrel is variable among patients,2 and low or incomplete platelet inhibition has been associated with increased risk for major adverse cardiovascular events.3

Multiple mechanisms have been proposed for the variable response to clopidogrel, including reduced drug bioavailability, patient nonadherence, drug-drug interactions (eg, proton pump inhibitors), ventricular dysfunction, dyslipidemia, and diabetes. More recently, genetic polymorphisms have been discovered in the hepatic cytochrome 2C19 enzyme (CYP2C19) that is partially responsible for the bioactivation of clopidogrel (a prodrug).4 Initial studies have determined that carriers of the allelic variant . . . [Full Text of this Article]

Author Affiliations: Zena and Michael Wiener Cardiovascular Institute, and the Marie-Josee and Henry R. Kravis Cardiovascular Health Center, The Mount Sinai School of Medicine, New York, New York, and the Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain (Dr Fuster); and Mount Sinai Heart, Mount Sinai Medical Center, New York, New York (Dr Sweeny).
JAMA -- Clopidogrel and the Reduced-Function CYP2C19 Genetic Variant: A Limited Piece of the Overall Therapeutic Puzzle, October 27, 2010, Fuster and Sweeny 304 (16): 1839