Baseline platelet activity and response after clopidogrel in 257 diabetics among 822 patients with coronary artery disease

Victor Serebruany; Ilya Pokov; Wiktor Kuliczkowski; James Chesebro; Juan Badimon

doi:10.1160/TH08-03-0136

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2008; 100(01): 76-82
DOI: 10.1160/TH08-03-0136

Platelets and Blood Cells

Schattauer GmbH

Baseline platelet activity and response after clopidogrel in 257 diabetics among 822 patients with coronary artery disease

Victor Serebruany

¹HeartDrug™ Research Laboratories, Johns Hopkins University, Towson, Maryland, USA

,

Ilya Pokov

¹HeartDrug™ Research Laboratories, Johns Hopkins University, Towson, Maryland, USA

,

Wiktor Kuliczkowski

²Silesian Center for Heart Diseases, Zabrze, Poland

,

James Chesebro

³University of Massachusetts, Worcester, Massachusetts, USA

,

Juan Badimon

⁴Mount Sinai School of Medicine, New York, New York, USA

› Author Affiliations

Abstract

Summary

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.

Keywords

Diabetes mellitus - platelet pharmacology - antiplatelet agents

Full Text

References

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