title: Baseline platelet activity and response after clopidogrel in 257 diabetics among 822 patients with coronary artery disease.
abstract: The objective was to describe the indices of platelet aggregation and activation in a large cohort of diabetic patients with coronary artery disease (CAD). Recently, a number of observations have indicated that patients with diabetes mellitus (DM) exhibit persistent platelet activation, and low response after antiplatelet therapy, although no randomized data exist. We sought to define the baseline platelet biomarkers, and the patterns of response to aspirin and clopidogrel therapy in DM versus non-diabetic patients. Secondary post-hoc analyses were made of platelet activity biomarkers in the dataset which consisted of patients with documented CAD (n = 822), including those with DM (n = 257). Patients with DM exhibited higher baseline platelet activity by adenosine diphosphate (ADP)- (p = 0.0002), and collagen-induced (p = 0.03) aggregometry; Ultegra- (p = 0.0001), and PFA-100 (p = 0.02) analyzers; and expression of platelet/endothelial cell adhesion molecule-1 (PECAM-1) (p = 0.01), glycoprotein (GP) IIb/IIIa antigen (p = 0.001), and activity (p = 0.02), vitronectin receptor (p = 0.03), P selectin (p = 0.02), and intact epitope of PAR-1 thrombin receptor (p = 0.02). Antiplatelet response after clopidogrel in diabetics was impaired when compared with non-diabetics. In conclusion, diabetic patients exhibit high pretreatment platelet activity, and do not respond well to the available antiplatelet regimens when compared with similar patients without DM. The clinical implications of these findings are unknown but are potentially important. Considering worsened outcomes in this high-risk population, clinical trials in DM are urgently needed in order to define the optimal degree of platelet inhibition and suitability for more aggressive antiplatelet regimens.
authors.affiliation: HeartDrug Research Laboratories, Johns Hopkins University, Osler Medical Building, 7600 Osler Drive, Suite 307, Towson, Maryland, 21204, USA. heartdrug@aol.com
authors.forename: Victor
authors.initials: V
authors.lastname: Serebruany
authors.forename: Ilya
authors.initials: I
authors.lastname: Pokov
authors.forename: Wiktor
authors.initials: W
authors.lastname: Kuliczkowski
authors.forename: James
authors.initials: J
authors.lastname: Chesebro
authors.forename: Juan
authors.initials: J
authors.lastname: Badimon
mesh_terms: D000368:Aged; D001241:Aspirin / Q000627:therapeutic use; D015142:Baltimore; D015415:Biomarkers / Q000097:blood; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D003920:Diabetes Mellitus / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D010979:Platelet Function Tests; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin