Stroke Prevention by Cilostazol in Patients with Atherothrombosis

Meta-analysis of Placebo-controlled Randomized Trials

Shinichiro Uchiyama, Bart M Demaerschalk, Shinya Goto, Yukito Shinohara, Fumio Gotoh, William M. Stone, Samuel R. Money, Sun Uck Kwon

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Background: Cilostazol is an antiplatelet agent that inhibits phosphodiesterase III in platelets and vascular endothelium. Previous randomized controlled trials of cilostazol for prevention of cerebrovascular events have garnered mixed results. We performed a systematic review and meta-analysis of the randomized clinical trials in patients with atherothrombotic diseases to determine the effects of cilostazol on cerebrovascular, cardiac, and all vascular events, and on all major hemorrhagic events. Methods: Relevant trials were identified by searching MEDLINE, EMBASE, and the Cochrane Controlled Trial Registry for titles and abstracts. Data from 12 randomized controlled trials, involving 5674 patients, were analyzed for end points of cerebrovascular, cardiac, and major bleeding events. Searching, determination of eligibility, data extraction, and meta-analyses were conducted by multiple independent investigators. Results: Data were available in 3782, 1187, and 705 patients with peripheral arterial disease, cerebrovascular disease, and coronary stenting, respectively. Incidence of total vascular events was significantly lower in the cilostazol group compared with the placebo group (relative risk [RR], 0.86; 95% confidence interval [CI], 0.74-0.99; P=.038). This was particularly influenced by a significant decrease of incidence of cerebrovascular events in the cilostazol group (RR, 0.58; 95% CI, 0.43-0.78; P < .001). There was no significant intergroup difference in incidence of cardiac events (RR, 0.99; 95% CI, 0.83-1.17; P=.908) and serious bleeding complications (RR, 1.00; 95% CI, 0.66-1.51; P=.996). Conclusions: This first meta-analysis of cilostazol in patients with atherothrombosis demonstrated a significant risk reduction for cerebrovascular events, with no associated increase of bleeding risk.

Original languageEnglish (US)
Pages (from-to)482-490
Number of pages9
JournalJournal of Stroke and Cerebrovascular Diseases
Volume18
Issue number6
DOIs
StatePublished - Nov 2009

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Meta-Analysis
Randomized Controlled Trials
Stroke
Placebos
Confidence Intervals
Hemorrhage
Blood Vessels
Eligibility Determination
Incidence
Type 3 Cyclic Nucleotide Phosphodiesterases
Cerebrovascular Disorders
Peripheral Arterial Disease
Platelet Aggregation Inhibitors
Vascular Endothelium
Risk Reduction Behavior
MEDLINE
Registries
cilostazol
Blood Platelets
Research Personnel

Keywords

  • atherothrombosis
  • cerebrovascular disorders
  • cilostazol
  • Meta-analysis
  • phosphodiesterase inhibitor
  • platelet aggregation inhibitor
  • prevention
  • stroke
  • vascular endothelium

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery
  • Rehabilitation
  • Cardiology and Cardiovascular Medicine

Cite this

Stroke Prevention by Cilostazol in Patients with Atherothrombosis : Meta-analysis of Placebo-controlled Randomized Trials. / Uchiyama, Shinichiro; Demaerschalk, Bart M; Goto, Shinya; Shinohara, Yukito; Gotoh, Fumio; Stone, William M.; Money, Samuel R.; Kwon, Sun Uck.

In: Journal of Stroke and Cerebrovascular Diseases, Vol. 18, No. 6, 11.2009, p. 482-490.

Research output: Contribution to journalArticle

Uchiyama, Shinichiro ; Demaerschalk, Bart M ; Goto, Shinya ; Shinohara, Yukito ; Gotoh, Fumio ; Stone, William M. ; Money, Samuel R. ; Kwon, Sun Uck. / Stroke Prevention by Cilostazol in Patients with Atherothrombosis : Meta-analysis of Placebo-controlled Randomized Trials. In: Journal of Stroke and Cerebrovascular Diseases. 2009 ; Vol. 18, No. 6. pp. 482-490.
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abstract = "Background: Cilostazol is an antiplatelet agent that inhibits phosphodiesterase III in platelets and vascular endothelium. Previous randomized controlled trials of cilostazol for prevention of cerebrovascular events have garnered mixed results. We performed a systematic review and meta-analysis of the randomized clinical trials in patients with atherothrombotic diseases to determine the effects of cilostazol on cerebrovascular, cardiac, and all vascular events, and on all major hemorrhagic events. Methods: Relevant trials were identified by searching MEDLINE, EMBASE, and the Cochrane Controlled Trial Registry for titles and abstracts. Data from 12 randomized controlled trials, involving 5674 patients, were analyzed for end points of cerebrovascular, cardiac, and major bleeding events. Searching, determination of eligibility, data extraction, and meta-analyses were conducted by multiple independent investigators. Results: Data were available in 3782, 1187, and 705 patients with peripheral arterial disease, cerebrovascular disease, and coronary stenting, respectively. Incidence of total vascular events was significantly lower in the cilostazol group compared with the placebo group (relative risk [RR], 0.86; 95{\%} confidence interval [CI], 0.74-0.99; P=.038). This was particularly influenced by a significant decrease of incidence of cerebrovascular events in the cilostazol group (RR, 0.58; 95{\%} CI, 0.43-0.78; P < .001). There was no significant intergroup difference in incidence of cardiac events (RR, 0.99; 95{\%} CI, 0.83-1.17; P=.908) and serious bleeding complications (RR, 1.00; 95{\%} CI, 0.66-1.51; P=.996). Conclusions: This first meta-analysis of cilostazol in patients with atherothrombosis demonstrated a significant risk reduction for cerebrovascular events, with no associated increase of bleeding risk.",
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AU - Demaerschalk, Bart M

AU - Goto, Shinya

AU - Shinohara, Yukito

AU - Gotoh, Fumio

AU - Stone, William M.

AU - Money, Samuel R.

AU - Kwon, Sun Uck

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N2 - Background: Cilostazol is an antiplatelet agent that inhibits phosphodiesterase III in platelets and vascular endothelium. Previous randomized controlled trials of cilostazol for prevention of cerebrovascular events have garnered mixed results. We performed a systematic review and meta-analysis of the randomized clinical trials in patients with atherothrombotic diseases to determine the effects of cilostazol on cerebrovascular, cardiac, and all vascular events, and on all major hemorrhagic events. Methods: Relevant trials were identified by searching MEDLINE, EMBASE, and the Cochrane Controlled Trial Registry for titles and abstracts. Data from 12 randomized controlled trials, involving 5674 patients, were analyzed for end points of cerebrovascular, cardiac, and major bleeding events. Searching, determination of eligibility, data extraction, and meta-analyses were conducted by multiple independent investigators. Results: Data were available in 3782, 1187, and 705 patients with peripheral arterial disease, cerebrovascular disease, and coronary stenting, respectively. Incidence of total vascular events was significantly lower in the cilostazol group compared with the placebo group (relative risk [RR], 0.86; 95% confidence interval [CI], 0.74-0.99; P=.038). This was particularly influenced by a significant decrease of incidence of cerebrovascular events in the cilostazol group (RR, 0.58; 95% CI, 0.43-0.78; P < .001). There was no significant intergroup difference in incidence of cardiac events (RR, 0.99; 95% CI, 0.83-1.17; P=.908) and serious bleeding complications (RR, 1.00; 95% CI, 0.66-1.51; P=.996). Conclusions: This first meta-analysis of cilostazol in patients with atherothrombosis demonstrated a significant risk reduction for cerebrovascular events, with no associated increase of bleeding risk.

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