Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Cardiovascular Drugs and Therapy
Published in: Cardiovascular Drugs and Therapy 4/2022

16-04-2021 | Stroke | Review Article

Cilostazol: a Review of Basic Mechanisms and Clinical Uses

Authors: Riyad Y. Kherallah, Muzamil Khawaja, Michael Olson, Dominick Angiolillo, Yochai Birnbaum

Published in: Cardiovascular Drugs and Therapy | Issue 4/2022

Login to get access

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.
Literature
1.
Pearce L, Ghosh J, Counsell A, Serracino-Inglott F. Cilostazol and peripheral arterial disease. Expert Opin Pharmacother. 2008;9(15):2683–90.PubMedCrossRef
2.
Noé L, Peeters K, Izzi B, Van Geet C, Freson K. Regulators of platelet cAMP levels: clinical and therapeutic implications. Curr Med Chem. 2010;17(26):2897–905.PubMedCrossRef
3.
Gerhard-Herman M, Gornik HL, Barrett C, et al. 2016 AHA/ACC guideline on the management of patients with lower extremity peripheral artery disease: executive summary: a report of the american college of cardiology/american heart association task force on clinical practice guidelines. J Am Coll Cardiol. 2017;69(11):1465–508.PubMedCrossRef
4.
Colman RW. Platelet cyclic adenosine monophosphate phosphodiesterases: targets for regulating platelet-related thrombosis. Semin Thromb Hemost. 2004;30(4):451–60.PubMedCrossRef
5.
Elam NA, Heckman J, Crouse JR, et al. Effect of the novel antiplatelet agent cilostazol on plasma lipoproteins in patients with intermittent claudication. Arterioscler Thromb Vasc Biol. 1998;18(12):1942–7.PubMedCrossRef
6.
Chancharoenthana W, Leelahavanichkul A, Taratummarat S, Wongphom J, Tiranathanagul K, Eiam-Ong S. Cilostazol attenuates intimal hyperplasia in a mouse model of chronic kidney disease. PLoS One. 2017;12(12):e0187872.PubMedPubMedCentralCrossRef
7.
Lee S, Park S, Kim Y, Yun SC, Park DW, Lee CW, et al. A randomized, double-blind, multicenter comparison study of triple antiplatelet therapy with dual antiplatelet therapy to reduce restenosis after drug-eluting stent implantation in long coronary lesions: Results from the DECLARE-LONG II (drug-eluting stenting followed by cilostazol treatment reduces late restenosis in patients with long coronary lesions) trial. J Am Coll Cardiol. 2011;57(11):1264–70.PubMedCrossRef
8.
Ipema J, Roozendaal NC, Bax WA, de Borst GJ, de Vries J, Ünlü Ç. Medical adjunctive therapy for patients with chronic limb-threatening ischemia: a systematic review. J Cardiovasc Surg. 2019;60(6):642–51.
9.
Dawson DL, Cutler BS, Hiatt WR, Hobson RW II, Martin JD, Bortey EB, et al. A comparison of cilostazol and pentoxifylline for treating intermittent claudication. Am J Med. 2000;109(7):523–30.PubMedCrossRef
10.
Heo SH, Heo SH, Lee JS, et al. Effects of cilostazol against the progression of carotid IMT in symptomatic ischemic stroke patients. J Neurol. 2013;260(1):122–30.PubMedCrossRef
11.
Planchon SM. Abrogating the induction of type 2 diabetes mellitus secondary to statin therapy: Editorial to: “PTEN upregulation may explain the development of insulin resistance and type 2 diabetes with high dose statins” by Y. birnbaum et al. Cardiovasc Drugs Ther. 2014;28(5):393–4.PubMedCrossRef
12.
Bedenis R, Stewart M, Cleanthis M, Robless P, Mikhailidis DP, Stansby G. Cilostazol for intermittent claudication. Cochrane Database Syst Rev. 2014;2014(10):CD003748.PubMedCentral
13.
Kim JS, Kwon SU, Uchiyama S. Cilostazol research in Asia: can it be applied to european and american patients? International journal of stroke. Int J Stroke. 2015;10(1):1–9.PubMed
14.
15.
Wallis RM, Corbin JD, Francis SH, Ellis P. Tissue distribution of phosphodiesterase families and the effects of sildenafil on tissue cyclic nucleotides, platelet function, and the contractile responses of trabeculae carneae and aortic rings in vitro. Am J Cardiol. 1999;83(5):3–12.CrossRef
16.
Liu Y, Cone J, Le SN, et al. Cilostazol and dipyridamole synergistically inhibit human platelet aggregation. J Cardiovasc Pharmacol. 2004;44(2):266–73.PubMedCrossRef
17.
Yun S, Sim E, Goh R, Park J, Han J. Platelet activation: the mechanisms and potential biomarkers. BioMed research international. Biomed Res Int. 2016;2016:9060143–5.PubMedPubMedCentralCrossRef
18.
Paul S, Feoktistov I, Hollister AS, Robertson D, Biaggioni I. Adenosine inhibits the rise in intracellular calcium and platelet aggregation produced by thrombin: evidence that both effects are coupled to adenylate cyclase. Mol Pharmacol. 1990;37(6):870–5.PubMed
19.
Yan R, Yan R, Li S, Li S, Dai K, Dai K. The critical roles of cyclic AMP/cyclic AMP-dependent protein kinase in platelet physiology. Front Biol China. 2009;4(1):7–14.CrossRef
20.
Sudo T, Ito H, Kimura Y. Phosphorylation of the vasodilator-stimulated phosphoprotein (VASP) by the anti-platelet drug, cilostazol, in platelets. Platelets. 2003;14(6):381–90.PubMedCrossRef
21.
Kariyazono H, Nakamura K, Shinkawa T, Yamaguchi T, Sakata R, Yamada K. Inhibition of platelet aggregation and the release of P-selectin from platelets by cilostazol. Thromb Res. 2001;101(6):445–53.PubMedCrossRef
22.
Sun B, Le SN, Lin S, et al. New mechanism of action for cilostazol: interplay between adenosine and cilostazol in inhibiting platelet activation. J Cardiovasc Pharmacol. 2002;40(4):577–85.PubMedCrossRef
23.
Liu Y, Shakur Y, Yoshitake M, Kambayashi J. Cilostazol (pletal®): a dual inhibitor of cyclic nucleotide phosphodiesterase type 3 and adenosine uptake. Cardiovasc Drug Rev. 2001;19(4):369–86.PubMedCrossRef
24.
Guarino ML, Massimi I, Alemanno L, Conti L, Angiolillo DJ, Pulcinelli FM. MRP4 over-expression has a role on both reducing nitric oxide-dependent antiplatelet effect and enhancing ADP induced platelet activation. J Thromb Thrombolysis. 2020. https://​doi.​org/​10.​1007/​s11239-020-02214-4.
25.
Cheepala SB, Pitre A, Fukuda Y, Takenaka K, Zhang Y, Wang Y, et al. The ABCC4 membrane transporter modulates platelet aggregation. Blood. 2015;126(20):2307–19.PubMedPubMedCentralCrossRef
26.
Borgognone A, Pulcinelli FM. Reduction of cAMP and cGMP inhibitory effects in human platelets by MRP4-mediated transport. Thromb Haemost. 2012;108(5):955–62.PubMedCrossRef
27.
Massimi I, Lotti LV, Temperilli F, Mancone M, Sardella G, Calcagno S, et al. Enhanced platelet MRP4 expression and correlation with platelet function in patients under chronic aspirin treatment. Thromb Haemost. 2016;115(6):1100–10.CrossRef
28.
29.
Alemanno L, Massimi I, Klaus V, Guarino M, Maltese T, Frati L, et al. Impact of multidrug resistance protein-4 inhibitors on modulating platelet function and high on-aspirin treatment platelet reactivity. Thromb Haemost. 2018;118(3):490–501.PubMedCrossRef
30.
Angiolillo DJ. Antiplatelet therapy in type 2 diabetes mellitus. Current opinion in endocrinology, diabetes, and obesity. Curr Opin Endocrinol Diabetes Obes. 2007;14(2):124–31.PubMedCrossRef
31.
Angiolillo DJ, Capranzano P, Goto S, Aslam M, Desai B, Charlton RK, et al. 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. Eur Heart J. 2008;29(18):2202–11.PubMedCrossRef
32.
Capranzano P, Ferreiro JL, Ueno M, Capodanno D, Dharmashankar K, Darlington A, et al. Pharmacodynamic effects of adjunctive cilostazol therapy in patients with coronary artery disease on dual antiplatelet therapy: impact of high on-treatment platelet reactivity and diabetes mellitus status. Catheter Cardiovasc Interv. 2013;81(1):42–9.PubMedCrossRef
33.
Jeong Y, Hwang J, Kim I, et al. Adding cilostazol to dual antiplatelet therapy achieves greater platelet inhibition than high maintenance dose clopidogrel in patients with acute myocardial infarction: Results of the adjunctive cilostazol versus high maintenance dose clopidogrel in patients with AMI (ACCEL-AMI) study. Circulation. Cardiovascular interventions. Circ Cardiovasc Interv. 2010;3(1):17–26.PubMedCrossRef
34.
Tajima H, Izumi T, Miyachi S, et al. Association between CYP2C19 genotype and the additional effect of cilostazol to clopidogrel resistance in neuroendovascular therapy. Nagoya J Med Sci. 2018;80(2):207–15.PubMedPubMedCentral
35.
36.
Ohnuki Y, Ohnuki Y, Kohara S, Shimizu M, Takizawa S. Dual therapy with aspirin and cilostazol may improve platelet aggregation in noncardioembolic stroke patients: a pilot study. Intern Med. 2017;56(11):1307–13.PubMedPubMedCentralCrossRef
37.
Onoda K, Ohashi K, Hashimoto A, Okuda M, Shimono T, Nishikawa M, et al. Inhibition of platelet aggregation by combined therapy with aspirin and cilostazol after off-pump coronary artery bypass surgery. Ann Thorac Cardiovasc Surg. 2008;14(4):230–7.PubMed
38.
Adelstein RS, Conti MA, Hathaway DR, Klee CB. Phosphorylation of smooth muscle myosin light chain kinase by the catalytic subunit of adenosine 3': 5'-monophosphate-dependent protein kinase. J Biol Chem. 1978;253(23):8347–50.PubMedCrossRef
39.
Nishioka K, Nishida M, Ariyoshi M, Jian Z, Saiki S, Hirano M, et al. Cilostazol suppresses angiotensin II–Induced vasoconstriction via protein kinase A–mediated phosphorylation of the transient receptor potential canonical 6 channel. Arterioscler Thromb Vasc Biol. 2011;31(10):2278–86.PubMedCrossRef
40.
Manickavasagam S, Ye Y, Lin Y, Perez-Polo RJ, Huang MH, Lui CY, et al. The cardioprotective effect of a statin and cilostazol combination: relationship to akt and endothelial nitric oxide synthase activation. Cardiovasc Drugs Ther. 2007;21(5):321–30.PubMedCrossRef
41.
Wu S, Liu S, Huang M. Cilostazol, an inhibitor of type 3 phosphodiesterase, stimulates large-conductance, calcium-activated potassium channels in pituitary GH3 cells and pheochromocytoma PC12 cells. Endocrinology. 2004;145(3):1175–84.PubMedCrossRef
42.
Tanaka T, Ishikawa T, Hagiwara M, Onoda K, Itoh H, Hidaka H. Effects of cilostazol, a selective cAMP phosphodiesterase inhibitor on the contraction of vascular smooth muscle. Pharmacology. 1988;36(5):313–20.PubMedCrossRef
43.
Malliaris SD, Munabi NCO, Akelina Y, Ascherman JA. Topical cilostazol inhibits neointimal hyperplasia in a rat interposition vein graft model. Plast Reconstr Surg. 2014;134(6):895e–901e.PubMedCrossRef
44.
Takahashi S, Oida K, Fujiwara R, Maeda H, Hayashi S, Takai H, et al. Effect of cilostazol, a cyclic AMP phosphodiesterase inhibitor, on the proliferation of rat aortic smooth muscle cells in culture. J Cardiovasc Pharmacol. 1992;20(6):900–6.PubMedCrossRef
45.
Hattori Y, Suzuki K, Tomizawa A, Hirama N, Okayasu T, Hattori S, et al. Cilostazol inhibits cytokine-induced nuclear factor-κB activation via AMP-activated protein kinase activation in vascular endothelial cells. Cardiovasc Res. 2009;81(1):133–9.PubMedCrossRef
46.
Kim M, Park K, Lee K, et al. Cilostazol inhibits vascular smooth muscle cell growth by downregulation of the transcription factor E2F. Hypertension. 2005;45(4):552–6.PubMedCrossRef
47.
Omi H, Okayama N, Shimizu M, Fukutomi T, Nakamura A, Imaeda K, et al. Cilostazol inhibits high glucose-mediated endothelial-neutrophil adhesion by decreasing adhesion molecule expression via NO production. Microvasc Res. 2004;68(2):119–25.PubMedCrossRef
48.
Takigawa T, Tsurushima H, Suzuki K, Tsuruta W, Nakamura K, Matsumura A. Cilostazol suppression of arterial intimal hyperplasia is associated with decreased expression of sialyl lewis X homing receptors on mononuclear cells and E-selectin in endothelial cells. J Vasc Surg. 2012;55(2):506–16.PubMedCrossRef
49.
Fujinaga K, Onoda K, Yamamoto K, Imanaka-Yoshida K, Takao M, Shimono T, et al. Locally applied cilostazol suppresses neointimal hyperplasia by inhibiting tenascin-c synthesis and smooth muscle cell proliferation in free artery grafts. J Thorac Cardiovasc Surg. 2004;128(3):357–63.PubMedCrossRef
50.
Chen W, Chen Y, Lin K, Hsuan Ting C, Yeh Y. Cilostazol promotes vascular smooth muscles cell differentiation through the cAMP response element-binding protein-dependent pathway. Arterioscler Thromb Vasc Biol. 2011;31(9):2106–13.PubMedCrossRef
51.
Ito H, Uehara K, Matsumoto Y, et al. Cilostazol inhibits accumulation of triglyceride in aorta and platelet aggregation in cholesterol-fed rabbits. PLoS One. 2012;7(6):e39374.PubMedPubMedCentralCrossRef
52.
Motta NAV, Brito FCF. Cilostazol exerts antiplatelet and anti-inflammatory effects through AMPK activation and NF-kB inhibition on hypercholesterolemic rats. Fundam Clin Pharmacol. 2016;30(4):327–37.PubMedCrossRef
53.
Tani T, Uehara K, Sudo T, Marukawa K, Yasuda Y, Kimura Y. Cilostazol, a selective type III phosphodiesterase inhibitor, decreases triglyceride and increases HDL cholesterol levels by increasing lipoprotein lipase activity in rats. Atherosclerosis. 2000;152(2):299–305.PubMedCrossRef
54.
Rizzo M, Corrado E, Patti AM, Rini GB, Mikhailidis DP. Cilostazol and atherogenic dyslipidemia: a clinically relevant effect? Expert Opin Pharmacother. 2011;12(4):647–55.PubMedCrossRef
55.
Nakamura N, Hamazaki T, Johkaji H, Minami S, Yamazaki K, Satoh A, et al. Effects of cilostazol on serum lipid concentrations and plasma fatty acid composition in type 2 diabetic patients with peripheral vascular disease. Clin Exp Med. 2003;2(4):180–4.PubMedCrossRef
56.
Toyota T, Oikawa S, Abe R, Sano R, Suzuki N, Hisamichi S, et al. Effect of cilostazol on lipid, uric acid and glucose metabolism in patients with impaired glucose tolerance or type 2 diabetes mellitus: a double-blind, placebo-controlled study. Clin Drug Investig. 2001;21(5):325–35.CrossRef
57.
Bai Y, Muqier, Murakami H, et al. Cilostazol protects the heart against ischaemia reperfusion injury in a rabbit model of myocardial infarction: focus on adenosine, nitric oxide and mitochondrial ATP-sensitive potassium channels. Clin Exp Pharmacol Physiol. 2011;38(10):658–65.PubMedCrossRef
58.
Li J, Xiang X, Gong X, Shi Y, Yang J, Xu Z. Cilostazol protects mice against myocardium ischemic/reperfusion injury by activating a PPARγ/JAK2/STAT3 pathway. Biomed Pharmacother. 2017;94:995–1001.PubMedCrossRef
59.
Gendy AM, Amin MM, Al-Mokaddem A, Abd Ellah MF. Cilostazol mitigates mesenteric ischemia/reperfusion-induced lung lesion: contribution of PPAR-γ, NF-κB, and STAT3 crosstalk. Life Sci. 2021;266:118882.PubMedCrossRef
60.
Fujii T, Obara H, Matsubara K, Fujimura N, Yagi H, Hibi T, et al. Oral administration of cilostazol improves survival rate after rat liver ischemia/reperfusion injury. J Surg Res. 2017;213:207–14.PubMedCrossRef
61.
Birnbaum GD, Birnbaum I, Ye Y, Birnbaum Y. Statin-induced cardioprotection against ischemia-reperfusion injury: Potential drug-drug interactions. lesson to be learnt by translating results from animal models to the clinical settings. Cardiovasc Drugs Ther. 2015;29(5):461–7.PubMedCrossRef
62.
Merla R, Ye Y, Lin Y, Manickavasagam S, Huang MH, Perez-Polo RJ, et al. The central role of adenosine in statin-induced ERK1/2, akt, and eNOS phosphorylation. Am J Physiol Heart Circ Physiol. 2007;293(3):1918–28.CrossRef
63.
Honda F, Imai H, Ishikawa M, Kubota C, Shimizu T, Fukunaga M, et al. Cilostazol attenuates gray and white matter damage in a rodent model of focal cerebral ischemia. Stroke. 2006;37(1):223–8.PubMedCrossRef
64.
Senbokuya N, Kinouchi H, Kanemaru K, Ohashi Y, Fukamachi A, Yagi S, et al. Effects of cilostazol on cerebral vasospasm after aneurysmal subarachnoid hemorrhage: a multicenter prospective, randomized, open-label blinded end point trial: Clinical article. J Neurosurg. 2013;118(1):121–30.PubMedCrossRef
65.
Takagi T, Hara H. Protective effects of cilostazol against hemorrhagic stroke: current and future perspectives. Journal of pharmacological sciences. J Pharmacol Sci. 2016;131(3):155–61.PubMedCrossRef
66.
Lee JH, Park SY, Shin HK, Kim CD, Lee WS, Hong KW. Protective effects of cilostazol against transient focal cerebral ischemia and chronic cerebral hypoperfusion injury. CNS neuroscience & therapeutics. CNS Neurosci Ther. 2008;14(2):143–52.PubMedPubMedCentralCrossRef
67.
Lim J, Woo J, Shin Y. Cilostazol protects endothelial cells against lipopolysaccharide-induced apoptosis through ERK1/2- and P38 MAPK-dependent pathways. Korean J Intern Med. 2009;24(2):113–22.PubMedPubMedCentralCrossRef
68.
Watanabe T, Zhang N, Liu M, Tanaka R, Mizuno Y, Urabe T. Cilostazol protects against brain white matter damage and cognitive impairment in a rat model of chronic cerebral hypoperfusion. Stroke. 2006;37(6):1539–45.PubMedCrossRef
69.
Takagi T, Imai T, Mishiro K, Ishisaka M, Tsujimoto M, Ito H, et al. Cilostazol ameliorates collagenase-induced cerebral hemorrhage by protecting the blood–brain barrier. J Cereb Blood Flow Metab. 2016;37(1):123–39.CrossRef
70.
Torii H, Kubota H, Ishihara H, Suzuki M. Cilostazol inhibits the redistribution of the actin cytoskeleton and junctional proteins on the blood–brain barrier under hypoxia/reoxygenation. Pharmacol Res. 2007;55(2):104–10.PubMedCrossRef
71.
Beebe HG, Dawson DL, Cutler BS, Herd JA, Strandness DE, Bortey EB, et al. A new pharmacological treatment for intermittent claudication:: results of a randomized, multicenter trial. Arch Intern Med. 1999;159(17):2041–50.PubMedCrossRef
72.
Strandness DE, Dalman RL, Panian S, et al. Effect of cilostazol in patients with intermittent claudication: a randomized, double-blind, placebo-controlled study. Vascular and endovascular surgery. Vasc Endovasc Surg. 2002;36(2):83–91.CrossRef
73.
Soga Y, Yokoi H, Kawasaki T, et al. Efficacy of cilostazol after endovascular therapy for femoropopliteal artery disease in patients with intermittent claudication. J Am Coll Cardiol. 2009;53(1):48–53.PubMedCrossRef
74.
Iida O, Yokoi H, Soga Y. Cilostazol reduces angiographic restenosis after endovascular therapy for femoropopliteal lesions in the sufficient treatment of peripheral intervention by cilostazol study. J Vasc Surg. 2013;58(5):1423.CrossRef
75.
Soga Y, Takahara M, Iida O, Yamauchi Y, Hirano K, Fukunaga M, et al. Efficacy of CilostAzol for below-the-knee artery disease after balloon AnGioplasty in patiEnts with severe limb ischemia (CABBAGE trial). Ann Vasc Surg. 2017;45:22–8.PubMedCrossRef
76.
Douglas JS, Holmes DR, Murrah N, et al. Coronary stent restenosis in patients treated with cilostazol. Circulation. 2005;112(18):2826–32.PubMedCrossRef
77.
Park KW, Kang S, Park JJ, et al. Adjunctive cilostazol versus double-dose clopidogrel after drug-eluting stent implantation: the HOST-ASSURE randomized trial (harmonizing optimal strategy for treatment of coronary artery stenosis-safety & effectiveness of drug-eluting stents & anti-platelet regimen). JACC.Cardiovascular interventions. JACC Cardiovasc Interv. 2013;6(9):932–42.PubMedCrossRef
78.
Lee CH, Lee J, Park G, et al. Comparison of 1-year outcomes of triple (Aspirin + Clopidogrel + Cilostazol) versus dual antiplatelet therapy (Aspirin + Clopidogrel + Placebo) after implantation of second-generation drug-eluting stents into one or more coronary arteries: from the DECREASE-PCI trial. Am J Cardiol. 2018;121(4):423–9.PubMedCrossRef
79.
Shinohara Y, Katayama Y, Uchiyama S, Yamaguchi T, Handa S, Matsuoka K, et al. Cilostazol for prevention of secondary stroke (CSPS 2): an aspirin-controlled, double-blind, randomised non-inferiority trial. Lancet neurology. Lancet Neurol. 2010;9(10):959–68.PubMedCrossRef
80.
Toyoda K, Uchiyama S, Yamaguchi T, Easton JD, Kimura K, Hoshino H, et al. Dual antiplatelet therapy using cilostazol for secondary prevention in patients with high-risk ischaemic stroke in japan: a multicentre, open-label, randomised controlled trial. Lancet neurology. Lancet Neurol. 2019;18(6):539–48.PubMedCrossRef
81.
Kim BJ, Lee E, Kwon SU, et al. Prevention of cardiovascular events in asian patients with ischaemic stroke at high risk of cerebral haemorrhage (PICASSO): a multicentre, randomised controlled trial. Lancet neurology. Lancet Neurol. 2018;17(6):509–18.PubMedCrossRef
82.
Aboyans V, Ricco JB, Bartelink MEL, et al. 2017 ESC guidelines on the diagnosis and treatment of peripheral arterial diseases, in collaboration with the European Society for Vascular Surgery (ESVS): document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries Endorsed by: the European Stroke Organization (ESO) The Task Force for the Diagnosis and Treatment of Peripheral Arterial Diseases of the European Society of Cardiology (ESC) and of the European Society for Vascular Surgery (ESVS). Eur Heart J. 2018;39(9):763–816. https://​doi.​org/​10.​1093/​eurheartj/​ehx095.
83.
Abola MTB, Golledge J, Miyata T, Rha SW, Yan BP, Dy TC, et al. Asia-pacific consensus statement on the management of peripheral artery disease: a report from the asian pacific society of atherosclerosis and vascular disease asia-pacific peripheral artery disease consensus statement project committee. J Atheroscler Thromb. 2020;27(8):809–907.PubMedPubMedCentralCrossRef
84.
White JV, Dick F, Fitridge R, et al. Global vascular guidelines on the management of chronic limb-threatening ischemia. Eur J Vasc Endovasc Surg. 2019;58(1):S1–S109.e33.PubMedPubMedCentralCrossRef
85.
Kernan WN, Ovbiagele B, Black HR, Bravata DM, Chimowitz MI, Ezekowitz MD, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the american heart association/american stroke association. Stroke. 2014;45(7):2160–236.PubMedCrossRef
86.
87.
Ishihara H, Suzuki M. Japanese guidelines for the management of stroke 2015: overview of the chapter on subarachnoid hemorrhage. Nihon Rinsho. 2016;74(4):677–80.PubMed
88.
Fonseca V, Rendell M, Cariski AT, Hittel N, Zhang P. Cilostazol treatment of claudication in diabetic patients.(key global literature)(author abstract). Diabetes Care. 2003;26(10):2972.
89.
Olin JW, White CJ, Armstrong EJ, Kadian-Dodov D, Hiatt WR. Peripheral artery disease: evolving role of exercise, medical therapy, and endovascular options. J Am Coll Cardiol. 2016;67(11):1338–57.PubMedCrossRef
90.
Iida O, Nanto S, Uematsu M, Morozumi T, Kitakaze M, Nagata S. Cilostazol reduces restenosis after endovascular therapy in patients with femoropopliteal lesions. J Vasc Surg. 2008;48(1):144–9.PubMedCrossRef
91.
Megaly M, Abraham B, Saad M, et al. Outcomes with cilostazol after endovascular therapy of peripheral artery disease. Vasc Med. 2019;24(4):1358863X1983832-323.CrossRef
92.
Soga Y, Iida O, Kawasaki D, Hirano K, Yamaoka T, Suzuki K. Impact of cilostazol on angiographic restenosis after balloon angioplasty for infrapopliteal artery disease in patients with critical limb ischemia. Eur J Vasc Endovasc Surg. 2012;44(6):577–81.PubMedCrossRef
93.
Soga Y, Hamasaki T, Edahiro R, Iida O, Inoue N, Suzuki K, et al. Sustained effectiveness of cilostazol after endovascular treatment of femoropopliteal lesions: midterm follow-up from the sufficient treatment of peripheral intervention by cilostazol (STOP-IC) study. J Endovasc Ther. 2018;25(3):306–12.PubMedCrossRef
94.
Lee S, Park S, Kim Y, et al. Drug-eluting stenting followed by cilostazol treatment reduces late restenosis in patients with diabetes mellitus the DECLARE-DIABETES trial (A randomized comparison of triple antiplatelet therapy with dual antiplatelet therapy after drug-eluting stent implantation in diabetic patients). J Am Coll Cardiol. 2008;51(12):1181–7.PubMedCrossRef
95.
Neel JD, Kruse RL, Dombrovskiy VY, Vogel TR. Cilostazol and freedom from amputation after lower extremity revascularization. J Vasc Surg. 2015;61(4):960–4.PubMedCrossRef
96.
Miura T, Miyashita Y, Soga Y, Hozawa K, Doijiri T, Ikeda U, et al. Drug-eluting versus bare-metal stent implantation with or without cilostazol in the treatment of the superficial femoral artery: the DEBATE in SFA study. Circ Cardiovasc Interv. 2018;11(8):e006564.PubMedCrossRef
97.
Zen K, Takahara M, Iida O, Soga Y, Kawasaki D, Nanto S, et al. Drug-eluting stenting for femoropopliteal lesions, followed by cilostazol treatment, reduces stent restenosis in patients with symptomatic peripheral artery disease. J Vasc Surg. 2016;65(3):720–5.CrossRef
98.
Bonaca MP, Bauersachs RM, Anand SS, Debus ES, Nehler MR, Patel MR, et al. Rivaroxaban in peripheral artery disease after revascularization. N Engl J Med. 2020;382(21):1994–2004.PubMedCrossRef
99.
Tsuchikane E, Fukuhara A, Kobayashi T, Kirino M, Yamasaki K, Kobayashi T, et al. Impact of cilostazol on restenosis after percutaneous coronary balloon angioplasty. Circulation. 1999;100(1):21–6.PubMedCrossRef
100.
Min P, Jung J, Ko Y, Choi D, Jang Y, Shim W. Effect of cilostazol on in-stent neointimal hyperplasia after coronary artery stenting: a quantative coronary angiography and volumetric intravascular ultrasound study. Circ J. 2007;71(11):1685–90.PubMedCrossRef
101.
Friedland SN, Eisenberg MJ, Shimony A. Meta-analysis of randomized controlled trials on effect of cilostazol on restenosis rates and outcomes after percutaneous coronary intervention. Am J Cardiol. 2012;109(10):1397–404.PubMedCrossRef
102.
Lee T, Lin Y, Liou C, Lee J, Peng T, Liu C. Comparison of long-term efficacy and safety between cilostazol and clopidogrel in chronic ischemic stroke: a nationwide cohort study. Ther Adv Chronic Dis. 2020;11:204062232093641–2040622320936418.CrossRef
103.
Noma K, Higashi Y. Cilostazol for treatment of cerebral infarction. Expert Opin Pharmacother. 2018;19(15):1719–26.PubMedCrossRef
104.
Uchiyama S, Sakai N, Toi S, Ezura M, Okada Y, Takagi M, et al. Final results of cilostazol-aspirin therapy against recurrent stroke with intracranial artery stenosis (CATHARSIS). Cerebrovascular diseases extra. Cerebrovasc Dis Extra. 2015;5(1):1–13.PubMedPubMedCentralCrossRef
105.
Kim BJ, Kwon SU, Park J, et al. Cilostazol versus aspirin in ischemic stroke patients with high-risk cerebral hemorrhage: Subgroup analysis of the PICASSO trial. Stroke. 2020;51(3):931–7.PubMedCrossRef
106.
McHutchison C, Blair GW, Appleton JP, et al. Cilostazol for secondary prevention of stroke and cognitive decline: systematic review and meta-analysis. Stroke (1970). 2020;51(8):2374–85.CrossRef
107.
Galyfos G, Sianou A. Cilostazol for secondary prevention of stroke: should the guidelines perhaps be extended? Vasc Spec Int. 2017;33(3):89–92.CrossRef
108.
Gröschel K, Riecker A, Schulz J, Ernemann U, Kastrup A. Systematic review of early recurrent stenosis after carotid angioplasty and stenting. Stroke. 2005;36(2):367–73.PubMedCrossRef
109.
Galyfos G, Geropapas G, Sigala F, Aggeli K, Sianou A, Filis K. Meta-analysis of studies evaluating the effect of cilostazol on major outcomes after carotid stenting. J Endovasc Ther. 2016;23(1):186–95.PubMedCrossRef
110.
111.
Hiatt WR, Money SR, Brass EP. Long-term safety of cilostazol in patients with peripheral artery disease: the CASTLE study (cilostazol: a study in long-term effects). J Vasc Surg. 2008;47(2):330–336.e2.PubMedCrossRef
112.
Goto S. Cilostazol: Potential mechanism of action for antithrombotic effects accompanied by a low rate of bleeding. Atheroscler Suppl. 2005;6(4):3–11.PubMedCrossRef
113.
Castellsague J, Perez-Gutthann S, Calingaert B, Bui C, Varas-Lorenzo C, Arana A, et al. Characterization of new users of cilostazol in the UK, spain, sweden, and germany: characterization of new users of cilostazol. Pharmacoepidemiol Drug Saf. 2017;26(6):615–24.PubMedPubMedCentralCrossRef
114.
115.
Sibbing D, Aradi D, Alexopoulos D, et al. Updated expert consensus statement on platelet function and genetic testing for guiding P2Y12 receptor inhibitor treatment in percutaneous coronary intervention. JACC Cardiovasc Interv. 2019;12(16):1521–37.PubMedCrossRef
116.
Kaikita K, Yoshimura H, Ishii M, Kudoh T, Yamada Y, Yamamoto E, et al. Tailored adjunctive cilostazol therapy based on CYP2C19 genotyping in patients with acute myocardial infarction ― the CALDERA-GENE study. Circ J. 2018;82(6):1517–25.PubMedCrossRef
117.
Tang Y, Wang W, Yang M, et al. Randomized comparisons of double-dose clopidogrel or adjunctive cilostazol versus standard dual antiplatelet in patients with high posttreatment platelet reactivity: Results of the CREATIVE trial. Circulation. 2018;137(21):2231–45.PubMedCrossRef
118.
Strisciuglio T, Franco D, Di Gioia G, et al. Impact of genetic polymorphisms on platelet function and response to anti platelet drugs. Cardiovasc Diagn Ther. 2018;8(5):610–20.
Metadata
Title
Cilostazol: a Review of Basic Mechanisms and Clinical Uses
Authors
Riyad Y. Kherallah
Muzamil Khawaja
Michael Olson
Dominick Angiolillo
Yochai Birnbaum
Publication date
16-04-2021
Publisher
Springer US
Published in
Cardiovascular Drugs and Therapy / Issue 4/2022
Print ISSN: 0920-3206
Electronic ISSN: 1573-7241
DOI
https://doi.org/10.1007/s10557-021-07187-x

Other articles of this Issue 4/2022

Cardiovascular Drugs and Therapy 4/2022 Go to the issue

Original Article

Berberine Reverses Nitroglycerin Tolerance through Suppressing Protein Kinase C Alpha Activity in Vascular Smooth Muscle Cells

Original Article

A Non-inferiority, Randomized Clinical Trial Comparing Paclitaxel-Coated Balloon Versus New-Generation Drug-Eluting Stents on Angiographic Outcomes for Coronary De Novo Lesions

Original Article

Empagliflozin Disrupts a Tnfrsf12a-Mediated Feed Forward Loop That Promotes Left Ventricular Hypertrophy

Invited Review Article

Searching for Preclinical Models of Acute Decompensated Heart Failure: a Concise Narrative Overview and a Novel Swine Model

Review Article

Non-Vitamin K Antagonist Oral Anticoagulants (NOACs) Versus Warfarin in Patients with Atrial Fibrillation and (Morbid) Obesity or Low Body Weight: a Systematic Review and Meta-Analysis

Original Article

Proton Pump Inhibitor Co-Therapy in Patients with Atrial Fibrillation Treated with Oral Anticoagulants and a Prior History of Upper Gastrointestinal Tract Bleeding

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits