Effect of cilostazol on platelet reactivity among patients with peripheral artery disease on clopidogrel therapy

Dagmar F. Hernandez-Suarez; Hector Núñez-Medina; Stuart A. Scott; Angel Lopez-Candales; Jose M. Wiley; Mario J. Garcia; Kyle Melin; Karid Nieves-Borrero; Christina Rodriguez-Ruiz; Lorraine Marshall; Jorge Duconge

doi:10.1515/dmpt-2017-0032

Article

Effect of cilostazol on platelet reactivity among patients with peripheral artery disease on clopidogrel therapy

Dagmar F. Hernandez-Suarez , Hector Núñez-Medina , Stuart A. Scott , Angel Lopez-Candales , Jose M. Wiley , Mario J. Garcia , Kyle Melin , Karid Nieves-Borrero , Christina Rodriguez-Ruiz , Lorraine Marshall and Jorge Duconge

Published/Copyright: February 6, 2018

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From the journal Drug Metabolism and Personalized Therapy Volume 33 Issue 1

Abstract

Background:

Antiplatelet therapy with clopidogrel is recommended to reduce cardiovascular events in patients with peripheral artery disease (PAD); however, clopidogrel efficacy has not been adequately studied in this patient population. Therefore, we aimed to determine the effects of cilostazol therapy on platelet reactivity among PAD patients on clopidogrel.

Methods:

We performed a cross-sectional pilot study of 46 Puerto Rican patients diagnosed with PAD. The cohort was divided based on use of clopidogrel and cilostazol (n=24) or clopidogrel alone (n=22). Platelet function was measured ex vivo using the VerifyNow P2Y12 assay. Genomic DNA was extracted from peripheral blood samples using the QIAamp DNA Blood Midi Kit, which was subjected to candidate variant genotyping (CYP2C19, ABCB1, PON1 and P2RY12) using TaqMan quantitative polymerase chain reaction assays. All analyses were performed using SAS version 9.4 (SAS Institute).

Results:

Among all enrolled patients, 18 (39%) had high on-treatment platelet reactivity (HTPR). The mean platelet reactivity was 207±53 (range, 78–325) with higher P2Y12 reaction units in the non-cilostazol group, 224±45 vs. 191±55 on the cilostazol group (p=0.03). No significant differences were observed in the clinical or genetic variables between the two groups. A multiple regression analysis determined that history of diabetes mellitus (p=0.03), use of cilostazol (p=0.03) and hematocrit (p=0.02) were independent predictors of platelet reactivity.

Conclusions:

In Puerto Rican PAD patients on clopidogrel therapy, history of diabetes mellitus, use of cilostazol and hematocrit are independent predictors of platelet reactivity. Adjunctive cilostazol therapy may enhance clopidogrel efficacy among PAD patients with HTPR.

Keywords: cilostazol; clopidogrel; peripheral artery disease; platelet reactivity

Corresponding author: Dagmar F. Hernandez-Suarez, MD, Medicine Division, University of Puerto Rico School of Medicine, Medical Sciences Building, PO Box 365067, San Juan 00936-5067, Puerto Rico, Phone: +(787) 758-2525, Fax: +(787) 754-1739

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: This study was funded by the National Institute of Health (NIH) Award Numbers U54MD007600, R25MD007607, TL1TR001434-3, S21MD001830, SC1HL123911 and K23GM104401. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Received: 2017-11-2

Accepted: 2017-12-18

Published Online: 2018-2-6

Published in Print: 2018-3-28

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Articles in the same Issue

https://doi.org/10.1515/dmpt-2017-0032

Keywords for this article

cilostazol; clopidogrel; peripheral artery disease; platelet reactivity