Impact of adjunctive cilostazol therapy on platelet function profiles in patients with and without diabetes mellitus on aspirin and clopidogrel therapy
| Autor: | Davide Capodanno, Sabrina Sumner, Piera Capranzano, Bhaloo Desai, Masafumi Ueno, Kodlipet Dharmashankar, Luis A. Guzman, Lyndon C. Box, Theodore A. Bass, Martin M. Zenni, Ronald K. Charlton, José Luis Ferreiro, Andrew Darlington, Dominick J. Angiolillo |
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| Rok vydání: | 2011 |
| Předmět: |
Blood Platelets
Male medicine.medical_specialty Ticlopidine Platelet Function Tests Tetrazoles 030204 cardiovascular system & hematology Placebo Gastroenterology 03 medical and health sciences 0302 clinical medicine P2Y12 Double-Blind Method Internal medicine Diabetes Mellitus Humans Medicine Platelet Prospective Studies 030212 general & internal medicine Aged Aspirin Cross-Over Studies business.industry Thrombin Hematology Middle Aged Clopidogrel Crossover study Receptors Purinergic P2Y12 Cilostazol Chemotherapy Adjuvant Anesthesia Pharmacodynamics Female business Platelet Aggregation Inhibitors Signal Transduction medicine.drug |
| Zdroj: | Thrombosis and Haemostasis. 106:253-262 |
| ISSN: | 2567-689X 0340-6245 |
| DOI: | 10.1160/th11-01-0041 |
| Popis: | SummaryCilostazol 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. |
| Databáze: | OpenAIRE |
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