Impact of adjunctive cilostazol therapy on platelet function profiles in patients with and without diabetes mellitus on aspirin and clopidogrel therapy

Dominick J. Angiolillo; Piera Capranzano; Jose Luis Ferreiro; Masafumi Ueno; Davide Capodanno; Kodlipet Dharmashankar; Andrew Darlington; Sabrina Sumner; Bhaloo Desai; Ronald K. Charlton; Lyndon C. Box; Martin M. Zenni; Luis A. Guzman; Theodore A. Bass

doi:10.1160/TH11-01-0041

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2011; 106(02): 253-262
DOI: 10.1160/TH11-01-0041

Theme Issue Article

Schattauer GmbH

Impact of adjunctive cilostazol therapy on platelet function profiles in patients with and without diabetes mellitus on aspirin and clopidogrel therapy

Dominick J. Angiolillo

¹Division of Cardiology, University of Florida College of Medicine Jacksonville, Jacksonville, Florida, USA

,

Piera Capranzano

¹Division of Cardiology, University of Florida College of Medicine Jacksonville, Jacksonville, Florida, USA

,

Jose Luis Ferreiro

¹Division of Cardiology, University of Florida College of Medicine Jacksonville, Jacksonville, Florida, USA

,

Masafumi Ueno

¹Division of Cardiology, University of Florida College of Medicine Jacksonville, Jacksonville, Florida, USA

,

Davide Capodanno

¹Division of Cardiology, University of Florida College of Medicine Jacksonville, Jacksonville, Florida, USA

,

Kodlipet Dharmashankar

¹Division of Cardiology, University of Florida College of Medicine Jacksonville, Jacksonville, Florida, USA

,

Andrew Darlington

¹Division of Cardiology, University of Florida College of Medicine Jacksonville, Jacksonville, Florida, USA

,

Sabrina Sumner

¹Division of Cardiology, University of Florida College of Medicine Jacksonville, Jacksonville, Florida, USA

,

Bhaloo Desai

¹Division of Cardiology, University of Florida College of Medicine Jacksonville, Jacksonville, Florida, USA

,

Ronald K. Charlton

²Jacksonville Transplant Center, Shands Jacksonville, Jacksonville, Florida, USA

,

Lyndon C. Box

¹Division of Cardiology, University of Florida College of Medicine Jacksonville, Jacksonville, Florida, USA

,

Martin M. Zenni

¹Division of Cardiology, University of Florida College of Medicine Jacksonville, Jacksonville, Florida, USA

,

Luis A. Guzman

¹Division of Cardiology, University of Florida College of Medicine Jacksonville, Jacksonville, Florida, USA

,

Theodore A. Bass

¹Division of Cardiology, University of Florida College of Medicine Jacksonville, Jacksonville, Florida, USA

› Author Affiliations

Abstract

Summary

Cilostazol is a platelet inhibitor which when added to aspirin and clopidogrel has shown to reduce the risk of recurrent ischaemic events without an increase in bleeding. These clinical benefits have shown to be more pronounced in patients with diabetes mellitus (DM). However, it remains unknown whether cilostazol exerts different pharmacodynamic effects in patients with and without DM. This was a randomised, double-blind, placebo-controlled, cross-over pharmacodynamic study comparing platelet function in patients with and without DM on aspirin and clopidogrel therapy. Patients (n=111) were randomly assigned to either cilostazol 100 mg or placebo twice daily for 14 days and afterwards crossed-over treatment for another 14 days. Platelet function was performed at baseline, 14 days post-randomisation, and 14 days post-cross-over. Functional testing to assess P2Y₁₂ signalling included flow cytometric analysis of phosphorylation status of vasodilatorstimulated phosphoprotein measured by P2Y₁₂ reactivity index (PRI), light transmittance aggregometry and VerifyNow. Thrombin generation processes were also studied using thrombelastography. Significantly lower PRI values were observed following treatment with cilostazol compared with placebo both in DM and non-DM groups (p < 0.0001). The absolute between-treatment differences of PRI between groups was a 35.1% lower in patients with DM (p=0.039). Similar results were obtained using all other functional measures assessing P2Y₁₂ signalling. Thrombin generation was not affected by cilostazol. Cilostazol reduces platelet reactivity both in patients with and without DM, although these pharmacodynamic effects are enhanced in patients with DM. Despite the marked platelet inhibition, cilostazol does not alter thrombin-mediated haemostatic processes, which may explain its ischaemic benefit without the increased risk of bleeding.

Keywords

Diabetes mellitus - coronary artery disease - platelets

Full Text

References

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