title: CYP2C19*2/ABCB1-C3435T polymorphism and risk of cardiovascular events in coronary artery disease patients on clopidogrel: is clinical testing helpful?
abstract: BACKGROUND
  Studies evaluating CYP2C19*2 and ABCB1-C3435T polymorphisms have shown conflicting results. We performed this meta-analysis to evaluate role of clinical testing for these polymorphisms in CAD patients on clopidogrel.
  
  
  METHODS
  19,601 patients from 14 trials were analyzed. The endpoints were major adverse cardiovascular events (MACE), cardiovascular (CV) death, stent thrombosis (ST), myocardial infarction (MI), stroke and major bleeding. Combined relative risks (RR) with 95% confidence intervals (CI) were computed for each outcome by using standard methods of meta-analysis and test parameters were computed.
  
  
  RESULTS
  CYP2C19*2 polymorphism was associated with higher risk of MACE [RR: 1.28, CI: 1.06-1.54; p=0.009], CV death [RR: 3.21, CI: 1.65-6.23; p=0.001], MI [RR: 1.36, CI: 1.12-1.65; p=0.002], ST [RR: 2.41, CI: 1.69-3.41; p<0.001]. No difference was seen in major bleeding events [RR: 1.02, CI: 0.86-1.20; p=0.83]. Subgroup analysis showed similar results for elective PCI [RR: 1.34, CI: 1.01-1.76; p=0.03], and PCI with DES [RR: 1.53, CI: 1.029-1.269; p=0.03]. CYP2C19*2 polymorphism has very low sensitivity (28-58%), specificity (71-73%), positive predictive value (3-10%) but good negative predictive value (92-99%). ABCB1-C3435T polymorphism analysis revealed similar MACE [RR: 1.13, CI: 0.99-1.29; p=0.06], ST [RR: 0.88, CI: 0.52-1.47; p=0.63] and major bleeding [RR: 1.04, CI: 0.87-1.25; p=0.62] in both groups.
  
  
  CONCLUSIONS
  In CAD patients on clopidogrel therapy, CYP2C19*2 polymorphism is associated with significantly increased adverse cardiovascular events. However, due to the low positive predictive value, routine genetic testing cannot be recommended at present.
authors.affiliation: Department of Cardiology, Chicago Medical School, North Chicago, IL 60068, USA. drmukeshsingh@yahoo.com
authors.forename: Mukesh
authors.initials: M
authors.lastname: Singh
authors.forename: Tejaskumar
authors.initials: T
authors.lastname: Shah
authors.forename: Sasikanth
authors.initials: S
authors.lastname: Adigopula
authors.forename: Janos
authors.initials: J
authors.lastname: Molnar
authors.forename: Aziz
authors.initials: A
authors.lastname: Ahmed
authors.forename: Sandeep
authors.initials: S
authors.lastname: Khosla
authors.forename: Rohit
authors.initials: R
authors.lastname: Arora
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000235:genetics*; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000235:genetics*; D065731:Cytochrome P-450 CYP2C19; D006579:Heterozygote; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects / Q000235:genetics; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine