title: Sulfonylureas and on-clopidogrel platelet reactivity in type 2 diabetes mellitus patients.
abstract: Clopidogrel is a prodrug that needs to be converted in?vivo by several cytochrome (CYP) P450 iso-enzymes to become active. Both clopidogrel and the oral hypoglycemic drug class sulfonylureas are metabolized by the iso-enzyme CYP2C9. The objective of the study was to evaluate the relationship of sulfonylureas and on-clopidogrel platelet reactivity in type 2 diabetes mellitus patients undergoing elective coronary stent implantation. In this prospective, observational study, on-clopidogrel platelet reactivity was quantified using adenosine diphosphate (ADP)-induced light transmittance aggregometry in 139 type 2 diabetes mellitus patients undergoing elective coronary stent implantation treated with clopidogrel and aspirin. High on-clopidogrel platelet reactivity was defined as >70.7% platelet reactivity to 20 μmol/L ADP. A total of 53 patients (38.1%) were on concomitant treatment with sulfonylureas. The remaining 86 patients were on other hypoglycemic drugs. On-clopidogrel platelet reactivity was significantly higher in patients with concomitant sulfonylurea treatment as compared to patients without concomitant sulfonylurea treatment (for 5 μmol/L ADP: 46.0% ± 11.8 vs. 40.6% ± 16.0; p=0.035, adjusted p=0.032 and for 20 μmol/L ADP: 64.6% ± 10.8 vs. 58.7% ± 15.5; p=0.019, adjusted p=0.017). The concomitant use of sulfonylureas was associated with a 2.2-fold increased risk of high on-clopidogrel platelet reactivity (OR 2.2, 95% CI 1.1-4.7, p=0.039 and after adjustment for confounders: OR(adj) 2.0, 95% CI 1.0-5.7, p=0.048). Concomitant treatment with sulfonylureas might be associated with decreased platelet inhibition by clopidogrel in type 2 diabetes mellitus patients on dual antiplatelet therapy undergoing elective coronary stent implantation.
authors.affiliation: Department of Clinical Pharmacy, St. Antonius Hospital, Nieuwegein, The Netherlands.
authors.forename: Ankie M
authors.initials: AM
authors.lastname: Harmsze
authors.forename: Jochem W
authors.initials: JW
authors.lastname: Van Werkum
authors.forename: Fulya
authors.initials: F
authors.lastname: Moral
authors.forename: Jurri N M
authors.initials: JN
authors.lastname: Ten Berg
authors.forename: Christian M
authors.initials: CM
authors.lastname: Hackeng
authors.forename: Olaf H
authors.initials: OH
authors.lastname: Klungel
authors.forename: Anthonius
authors.initials: A
authors.lastname: De Boer
authors.forename: Vera H M
authors.initials: VH
authors.lastname: Deneer
mesh_terms: D000368:Aged; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism*; D000077144:Clopidogrel; D015331:Cohort Studies; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000473:pathology*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D010979:Platelet Function Tests; D013453:Sulfonylurea Compounds / Q000494:pharmacology / Q000627:therapeutic use; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D007004:Hypoglycemic Agents; D010975:Platelet Aggregation Inhibitors; D013453:Sulfonylurea Compounds; D003577:Cytochrome P-450 Enzyme System; D000077144:Clopidogrel; D013988:Ticlopidine