title: Value of platelet pharmacogenetics in common clinical practice of patients with ST-segment elevation myocardial infarction.
abstract: BACKGROUND
  Antiplatelet drug resistance is a well-known problem, causing recurrent cardiovascular events. Multiple genetic polymorphisms have been related to antiplatelet resistance by several large trials, however data from common clinical practice is limited. We examined the influence of previously described polymorphisms, related to aspirin and clopidogrel resistance, on treatment outcome in a real life unselected population of patients presenting with ST-segment elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention.
  
  
  RESULTS
  This cohort study consisted of 1327 patients with STEMI. Patients were treated according to a standardized guideline-based protocol. Nine polymorphisms, COX1 (-842A>G), P2Y1 (893C>T), GPIa (807C>T), GPIIIa (PlA1/A2), CYP2C19 (*2, *3 and *17), ABCB1 (3435T>C) and PON1 (576A>G), were genotyped. During 1 year of follow up the primary endpoint, a composite of cardiac death or recurrent myocardial infarction, was reached in 86 patients. The COX1 and CYP2C19*2 polymorphisms were associated with the primary endpoint, HR 2.55 (95% CI 1.48-4.40), P=0.001 and HR 2.03 (1.34-3.09) P=0.001, respectively. The combined analysis demonstrated a 2.5-fold increased risk for individuals with ≥ 2 risk alleles, P=6.9 × 10(-9). The association of COX1 was driven by mortality related events whereas that of CYP2C19*2 was mainly attributed to myocardial infarction and stent thrombosis.
  
  
  CONCLUSIONS
  In this unselected, real life population of STEMI patient on dual-antiplatelet therapy, the polymorphisms COX1 -842A>G and CYP2C19*2 were determinants of thrombotic complications during follow-up. We show that in a clinical setting, testing for these polymorphisms could be of value in the identification of STEMI patients at risk for recurrent cardiovascular events.
authors.affiliation: Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Jeffrey J W
authors.initials: JJ
authors.lastname: Verschuren
authors.forename: Helèn
authors.initials: H
authors.lastname: Boden
authors.forename: Judith A M
authors.initials: JA
authors.lastname: Wessels
authors.forename: Bas L
authors.initials: BL
authors.lastname: van der Hoeven
authors.forename: Stella
authors.initials: S
authors.lastname: Trompet
authors.forename: Bastiaan T
authors.initials: BT
authors.lastname: Heijmans
authors.forename: Hein
authors.initials: H
authors.lastname: Putter
authors.forename: Henk-Jan
authors.initials: HJ
authors.lastname: Guchelaar
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Schalij
authors.forename: J Wouter
authors.initials: JW
authors.lastname: Jukema
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D000077144:Clopidogrel; D015331:Cohort Studies; D003328:Coronary Thrombosis / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D051545:Cyclooxygenase 1 / Q000235:genetics*; D065731:Cytochrome P-450 CYP2C19; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D010597:Pharmacogenetics / Q000379:methods*; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011159:Population Surveillance / Q000379:methods; D015607:Stents / Q000009:adverse effects; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human; D013988:Ticlopidine