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Cilostazol: a Review of Basic Mechanisms and Clinical Uses

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Abstract

Primarily used in the treatment of intermittent claudication, cilostazol is a 2-oxyquinolone derivative that works through the inhibition of phosphodiesterase III and related increases in cyclic adenosine monophosphate (cAMP) levels. However, cilostazol has been implicated in a number of other basic pathways including the inhibition of adenosine reuptake, the inhibition of multidrug resistance protein 4, among others. It has been observed to exhibit antiplatelet, antiproliferative, vasodilatory, and ischemic-reperfusion protective properties. As such, cilostazol has been investigated for clinical use in a variety of settings including intermittent claudication, as an adjunctive for reduction of restenosis after coronary and peripheral endovascular interventions, and in the prevention of secondary stroke, although its widespread implementation for indications other than intermittent claudication has been limited by relatively modest effect sizes and lack of studies in western populations. In this review, we highlight the pleiotropic effects of cilostazol and the evidence for its clinical use.

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Authors and Affiliations

  1. Department of Medicine, Baylor College of Medicine, Houston, TX, USA

    Riyad Y. Kherallah, Muzamil Khawaja & Michael Olson

  2. Division of Cardiology, University of Florida College of Medicine, Jacksonville, FL, USA

    Dominick Angiolillo

  3. Section of Cardiology, Department of Medicine, Baylor College of Medicine, 7200 Cambridge Street, Houston, TX, USA

    Yochai Birnbaum

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  1. Riyad Y. Kherallah
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Contributions

R.Y.K. performed the primary literature review, wrote the first draft of the manuscript, made subsequent revisions, and created the cilostazol mechanism of action figure. M.K. performed the primary literature search, wrote sections of the first draft, and made subsequent revisions. M.O. performed the primary literature search, wrote sections of the first draft, and made subsequent revisions. D.A. provided expert feedback and made revisions. Y.B. was responsible for the primary conception of the review topic, provided expert feedback, made edits, and provided supervision.

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Correspondence to Yochai Birnbaum.

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Competing Interests

D.J.A. declares that he has received consulting fees or honoraria from Abbott, Amgen, Aralez, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, Daiichi-Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, PhaseBio, PLx Pharma, Pfizer, Sanofi, and The Medicines Company and has received payments for participation in review activities from CeloNova and St. Jude Medical, outside the present work. D.J.A. also declares that his institution has received research grants from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Matsutani Chemical Industry Co., Merck, Novartis, Osprey Medical, Renal Guard Solutions, and Scott R. MacKenzie Foundation. Y.B declares that he has received research grants from AstraZeneca

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Kherallah, R.Y., Khawaja, M., Olson, M. et al. Cilostazol: a Review of Basic Mechanisms and Clinical Uses. Cardiovasc Drugs Ther 36, 777–792 (2022). https://doi.org/10.1007/s10557-021-07187-x

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