Cilostazol stroke prevention study: A placebo-controlled double-blind trial for secondary prevention of cerebral infarction.

Cilostazol, an antiplatelet drug that increases the cyclic adenosine monophosphate (AMP) levels in platelets via inhibition of cyclic AMP phosphodiesterase, has been used in chronic arterial occlusive disease. The purpose of the present study was to examine the effects of cilostazol on the recurrence of cerebral infarction using a multicenter, randomized, placebo-controlled, double-blind clinical trial method. Patients who suffered from cerebral infarction at 1 to 6 months before the trial were enrolled between April 1992 and March 1996. Oral administration of cilostazol (100 mg twice daily) or placebo was randomly assigned to the patients and continued until February 1997. The primary endpoint was the recurrence of cerebral infarction. In total, 1,095 patients were enrolled. An analysis based on 1,052 eligible patients (526 given cilostazol and 526 given placebo) showed that the cilostazol treatment achieved a significant relative-risk reduction (41.7%; confidence interval [CI], 9.2% to 62.5%) in the recurrence of cerebral infarction as compared with the placebo treatment (P=.0150). Intention-to-treat analysis of 1,067 patients also showed a significant relative-risk reduction (42.3%; CI, 10.3% to 62.9%, P=.0127). No clinically significant adverse drug reactions of cilostazol were encountered. Long-term administration of cilostazol was effective and safe in the secondary prevention of cerebral infarction.

[1]  Y. Ohashi,et al.  Design and organization of the cilostazol stroke prevention study , 2000 .

[2]  J. Crouse,et al.  Effect of the novel antiplatelet agent cilostazol on plasma lipoproteins in patients with intermittent claudication. , 1998, Arteriosclerosis, thrombosis, and vascular biology.

[3]  D. Dawson,et al.  Cilostazol has beneficial effects in treatment of intermittent claudication: results from a multicenter, randomized, prospective, double-blind trial. , 1998, Circulation.

[4]  Local.  Asia Pacific Consensus Forum on Stroke Management. , 1998, Stroke.

[5]  Yasuo Ikeda,et al.  Inhibition of shear stress-induced platelet aggregation by cilostazol, a specific inhibitor of cGMP-inhibited phosphodiesterase, in vitro and ex vivo. , 1997, Life sciences.

[6]  K. Welch.  Primer on cerebrovascular diseases , 1997 .

[7]  C. Helgason.  Mechanisms of Antiplatelet Agents and The Prevention of Stroke , 1997 .

[8]  M. Dennis.  A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee , 1996 .

[9]  David Schultz,et al.  A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE) , 1996, The Lancet.

[10]  H. Ueki,et al.  Involvement of the rapid increase in cAMP content in the vanadate-stimulated release of lipoprotein lipase activity from rat fat pads. , 1996, Biological & pharmaceutical bulletin.

[11]  H. Diener,et al.  European Stroke Prevention Study 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke 1 1 ESPS-2 Writing Committee , 1996, Journal of the Neurological Sciences.

[12]  D. Clement.  A randomised, blinded, trial of Clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE) , 1996 .

[13]  Y. Kimura.  [Selective type III phosphodiesterase inhibitor as an antithrombotic agent]. , 1995, Nihon yakurigaku zasshi. Folia pharmacologica Japonica.

[14]  J. Sparks,et al.  Regulation of VLDL secretion in primary culture of rat hepatocytes: involvement of cAMP and cAMP‐dependent protein kinases , 1994, European journal of clinical investigation.

[15]  Collaborative overview of randomised trials of antiplatelet therapy--I: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. Antiplatelet Trialists' Collaboration. , 1994, BMJ.

[16]  Sadao Takahashi,et al.  Effect of Cilostazol, a Cyclic AMP Phosphodiesterase Inhibitor, on the Proliferation of Rat Aortic Smooth Muscle Cells in Culture , 1992, Journal of cardiovascular pharmacology.

[17]  M. Laakso,et al.  The European Stroke Prevention Study , 1991, Neurology.

[18]  S. Kobayashi,et al.  Increased external carotid artery blood flow in headache patients induced by cilostazol. Preliminary communication. , 1990, Arzneimittel-Forschung.

[19]  Robert A. Zimmerman,et al.  Special report from the National Institute of Neurological Disorders and Stroke. Classification of cerebrovascular diseases III. , 1990, Stroke.

[20]  T. Tani,et al.  Potentiation of anti-platelet aggregating activity of cilostazol with vascular endothelial cells. , 1990, Thrombosis research.

[21]  Kortaro Tanaka,et al.  Effects of a selective inhibitor of cyclic AMP phosphodiesterase on the pial microcirculation in feline cerebral ischemia. , 1989, Stroke.

[22]  M. Gent,et al.  The Canadian American Ticlopidine Study (CATS) in thromboembolic stroke. , 1989, Lancet.

[23]  M. Hagiwara,et al.  Effects of cilostazol, a selective cAMP phosphodiesterase inhibitor on the contraction of vascular smooth muscle. , 1988, Pharmacology.

[24]  J. Grotta.  Current medical and surgical therapy for cerebrovascular disease. , 1987, The New England journal of medicine.

[25]  M. Murata,et al.  Comparison of the inhibitory effects of cilostazol, acetylsalicylic acid and ticlopidine on platelet functions ex vivo. Randomized, double-blind cross-over study. , 1987, Arzneimittel-Forschung.

[26]  H. Nakase,et al.  Effect of cilostazol on experimental cerebral infarction in rabbits. , 1986, Arzneimittel-Forschung.

[27]  S. P. Halenda,et al.  10 – Calcium and Cyclic AMP: Antagonistic Modulators of Platelet Function , 1985 .

[28]  G. Longenecker.  The Platelets : physiology and pharmacology , 1985 .

[29]  K. Yasuda,et al.  Hemodynamic effect of cilostazol on increasing peripheral blood flow in arteriosclerosis obliterans. , 1985, Arzneimittel-Forschung.

[30]  T. Tani,et al.  Effect of cilostazol on platelet aggregation and experimental thrombosis. , 1985, Arzneimittel-Forschung.

[31]  Tanaka Toshio,et al.  Purification of cyclic adenosine monophosphate phosphodiesterase from human platelets using new-inhibitor sepharose chromatography , 1984 .

[32]  H. Fukuzaki,et al.  Effect of cyclic AMP on cytoplasmic free calcium in human platelets stimulated by thrombin: direct measurement with quin2. , 1983, Thrombosis research.