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
1  Division of Cardiology, University of Florida College of Medicine Jacksonville, Jacksonville, Florida, USA
,
Piera Capranzano
1  Division of Cardiology, University of Florida College of Medicine Jacksonville, Jacksonville, Florida, USA
,
Jose Luis Ferreiro
1  Division of Cardiology, University of Florida College of Medicine Jacksonville, Jacksonville, Florida, USA
,
Masafumi Ueno
1  Division of Cardiology, University of Florida College of Medicine Jacksonville, Jacksonville, Florida, USA
,
Davide Capodanno
1  Division of Cardiology, University of Florida College of Medicine Jacksonville, Jacksonville, Florida, USA
,
Kodlipet Dharmashankar
1  Division of Cardiology, University of Florida College of Medicine Jacksonville, Jacksonville, Florida, USA
,
Andrew Darlington
1  Division of Cardiology, University of Florida College of Medicine Jacksonville, Jacksonville, Florida, USA
,
Sabrina Sumner
1  Division of Cardiology, University of Florida College of Medicine Jacksonville, Jacksonville, Florida, USA
,
Bhaloo Desai
1  Division of Cardiology, University of Florida College of Medicine Jacksonville, Jacksonville, Florida, USA
,
Ronald K. Charlton
2  Jacksonville Transplant Center, Shands Jacksonville, Jacksonville, Florida, USA
,
Lyndon C. Box
1  Division of Cardiology, University of Florida College of Medicine Jacksonville, Jacksonville, Florida, USA
,
Martin M. Zenni
1  Division of Cardiology, University of Florida College of Medicine Jacksonville, Jacksonville, Florida, USA
,
Luis A. Guzman
1  Division of Cardiology, University of Florida College of Medicine Jacksonville, Jacksonville, Florida, USA
,
Theodore A. Bass
1  Division of Cardiology, University of Florida College of Medicine Jacksonville, Jacksonville, Florida, USA
› Author Affiliations
Further Information

Publication History

Received: 27 January 2011

Accepted after major revision: 27 February 2011

Publication Date:
25 November 2017 (online)

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.