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European Heart Journal Advance Access originally published online on June 21, 2008
European Heart Journal 2008 29(18):2202-2211; doi:10.1093/eurheartj/ehn287
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

A randomized study assessing the impact of cilostazol on platelet function profiles in patients with diabetes mellitus and coronary artery disease on dual antiplatelet therapy: results of the OPTIMUS-2 study

Dominick J. Angiolillo1,*, Piera Capranzano1, Shinya Goto2, Mohammed Aslam1, Bhaloo Desai1, Ronald K. Charlton3, Yoshie Suzuki1, Lyndon C. Box1, Steven B. Shoemaker1, Martin M. Zenni1, Luis A. Guzman1 and Theodore A. Bass1

1 Division of Cardiology, University of Florida College of Medicine at Shands Jacksonville, 655 West 8th Street, Jacksonville, FL 32209, USA
2 Department of Medicine, Tokai University School of Medicine, Isehara, Japan
3 Jacksonville Transplant Center, Shands Jacksonville, Jacksonville, FL, USA

Received 26 February 2008; revised 2 June 2008; accepted 5 June 2008; online publish-ahead-of-print 21 June 2008.

* Corresponding author. Tel: +1 904 244 3933, Fax: +1 904 244 3102, Email: dominick.angiolillo{at}jax.ufl.edu

See page 2191 for the editorial comment on this article (doi:10.1093/eurheartj/ehn367)

Aims: Patients with type 2 diabetes mellitus (T2DM) have reduced platelet inhibition compared with non-diabetics following P2Y12 receptor blockade. Whether inhibition of P2Y12 signalling can be enhanced by adjunctive treatment with cilostazol in T2DM patients is unknown. The aim of this pilot study was to assess the functional impact of cilostazol in T2DM patients on standard aspirin and clopidogrel treatment.

Methods and results: This was a prospective, double-blind, double-dummy, placebo-controlled, randomized, cross-over platelet function study. T2DM patients on dual antiplatelet therapy were assigned to receive cilostazol 100 mg or placebo twice daily for 14 days and afterwards crossed-over treatment assignments for another 14 days. Platelet function was performed at three time points: at baseline, 14 days after randomization, and 14 days after treatment cross-over. The P2Y12 reactivity index, determined through flow cytometric assessment of the phosphorylation status of the vasodilator-stimulated phosphoprotein, was the primary endpoint measure. In addition to this flow cytometric evaluation, light transmittance aggregometry and VerifyNow testing were performed. A total of 25 T2DM patients were randomized; five patients discontinued treatment due to side effects. The P2Y12 reactivity index was significantly lower following cilostazol treatment compared with placebo (36.3 ± 20 vs. 59.9 ± 16%; P = 0.0002). All other P2Y12-specific functional assessments showed enhanced inhibition of this signalling pathway following treatment with cilostazol.

Conclusion: Adjunctive treatment with cilostazol in T2DM patients on standard dual antiplatelet therapy enhances inhibition of platelet P2Y12 signalling.

Key Words: Diabetes mellitus • Platelets • Thrombosis • Clopidogrel • Cilostazol


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Diabetic atherothrombosis: helpful adjunctive therapy
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EHJ 2008 10.1093/eurheartj/ehn367. [Extract] [Full Text]  



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Eur. Heart J., September 2, 2008; 29(18): 2191 - 2192.
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