Cilostazol for Secondary Stroke Prevention

Havenon, Adam de; Sheth, Kevin N; Madsen, Tracy E.; Johnston, Karen C.; Turan, Tanya N.; Toyoda, Kazunori; Williams, Olajide; Shoamanesh, Ashkan; Lansberg, Maarten G

doi:10.1161/strokeaha.121.035002

Cited by 30 publications

(19 citation statements)

References 94 publications

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“…A large-scale, prospective, double-blind, comparative trial is awaited in the United States and/or Europe. 21 Sub-analyses of CSPS.com will be published in the near future.…”

Section: Efficacy Of Cilostazol In Dual Antiplatelet Therapy For Prev...mentioning

confidence: 99%

Our Efforts for Ideal Stroke Prevention and Treatment in Japan

Yamaguchi

2022

Stroke

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In the present short review for the Sherman Award, Dr Yamaguchi introduces studies at the National Cerebral and Cardiovascular Center, Osaka, which included development of intravenous thrombolysis using low-dose alteplase that was officially approved in Japan, long-term dual antiplatelet therapy using cilostazol together with aspirin or clopidogrel, and others. He also discusses efforts to ensure the passage of the “Stroke and Cardiovascular Disease Control Act,” the aims of which are better primary prevention, better acute treatment, rehabilitation, and secondary prevention of stroke for people living in Japan.

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“…A large-scale, prospective, double-blind, comparative trial is awaited in the United States and/or Europe. 21 Sub-analyses of CSPS.com will be published in the near future.…”

Section: Efficacy Of Cilostazol In Dual Antiplatelet Therapy For Prev...mentioning

confidence: 99%

Our Efforts for Ideal Stroke Prevention and Treatment in Japan

Yamaguchi

2022

Stroke

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Section: Introductionmentioning

confidence: 99%

“…9 However, in the United States and Europe, its use for secondary prevention of ischemic stroke is off-label and less common. 9…”

Section: Introductionmentioning

confidence: 99%

“…8 It has been approved and widely used for secondary stroke prevention in Asian countries. 9 However, in the United States and Europe, its use for secondary prevention of ischemic stroke is offlabel and less common. 9 Cilostazol has been found to be non-inferior to aspirin in preventing ischemic stroke through several randomized controlled trials in Asians.…”

Section: Introductionmentioning

confidence: 99%

“…9 However, in the United States and Europe, its use for secondary prevention of ischemic stroke is offlabel and less common. 9 Cilostazol has been found to be non-inferior to aspirin in preventing ischemic stroke through several randomized controlled trials in Asians. [10][11][12] The Cilostazol versus Aspirin for Secondary Ischaemic Stroke Prevention (CASISP) trial in China showed that the hazard ratio (HR) of any stroke recurrence was 0.62 (95% confidence interval (CI), 0.30-1.26; P = 0.185) in cilostazol group compared to aspirin group and there were fewer brain bleeding events in the cilostazol group.…”

Section: Introductionmentioning

confidence: 99%

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Long-Term Comparison of Cilostazol versus Clopidogrel in Secondary Prevention of Noncardioembolic Ischemic Stroke

Lee

2023

Preprint

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Background: Cilostazol is a widely used antiplatelet drug for secondary stroke prevention in Asia, but its comparison with clopidogrel, another commonly used antiplatelet drug, is not well understood. This study aims to investigate the effectiveness and safety of cilostazol compared to clopidogrel for the secondary prevention of noncardioembolic ischemic stroke.<break><break>Methods: A retrospective comparative effectiveness research analysis was conducted using 1:1 propensity-matched data from insured individuals between Jan 1, 2012, and Dec 31, 2019. The study used administrative claims data in Health Insurance and Review Assessment in Korea. Patients with diagnosis codes for ischemic stroke without atrial fibrillation, heart failure, valvular diseases, and myocardial infarction were included and divided into two groups, those receiving cilostazol and those receiving clopidogrel. The primary outcome was a recurrent ischemic stroke. Secondary outcomes included all-cause death, myocardial infarction, hemorrhagic stroke, and a composite of these outcomes. The safety outcome was major gastrointestinal bleeding.<break><break>Results: A total of 4754 patients were included in the propensity-matched population, with a median age of 67 years, 3080 (40.7%) were male, and 4480 (59.3%) were female. The study found no statistically significant difference in recurrent ischemic stroke (cilostazol group vs clopidogrel group, 2.7% vs 3.2%; 95% CI, 0.62-1.21), the composite outcome of recurrent ischemic stroke, all-cause death, myocardial infarction, and hemorrhagic stroke (5.1% vs 5.5%; 95% CI 0.75-1.22), and major gastrointestinal bleeding (1.3% vs 1.5%; 95% CI 0.57-1.47) between cilostazol and clopidogrel use patients. In subgroup analysis, cilostazol was associated with a lower incidence of recurrent ischemic stroke compared to clopidogrel in hypertensive patients (2.5% vs 3.9%; interaction P = 0.41).<break><break>Conclusions: This real-world, comparative effectiveness research study suggests that cilostazol is effective and safe for noncardioembolic ischemic stroke and may be associated with better effectiveness in hypertensive patients compared to clopidogrel over an 8-year period.

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Cilostazol in patients with heart failure and preserved ejection fraction—The CLIP‐HFpEF trial

Aiad,

du Fay de Lavallaz,

Zhang

et al. 2024

ESC Heart Failure

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Background and AimsPatients with heart failure with preserved ejection fraction (HFpEF) tend to have low resting and exercise heart rates. Phosphodiesterase‐3 (PDE‐3) inhibitors improve heart rates, haemodynamics and symptoms in patients with HFpEF. Cilostazol is an oral PDE‐3 inhibitor used in peripheral artery disease. This study thought to evaluate the short‐term effects of cilostazol on health status, N‐terminal brain natriuretic peptide (NT‐proBNP) levels and mechanisms of action.MethodsThe effect of cilostazol was evaluated in 23 patients with HFpEF in a randomized placebo controlled multiple crossover trial (CLIP‐HFpEF). Participants received placebo or cilostazol for 1 week followed by three crossovers to the alternate assignment at weeks 2, 3 and 4. The primary endpoint was the Kansas City Cardiomyopathy Questionnaire (KCCQ‐12) overall summary score obtained at the end of each treatment period. NT‐proBNP was the secondary endpoint. In an exploratory mechanistic analysis, pulmonary artery (PA) pressures and heart rates were followed amongst the five participants with implanted pressure monitors.ResultsCilostazol improved the KCCQ score by 4.8 points (95% confidence interval, 2.0–7.7, P = 0.003). NT‐proBNP levels were 448 (154–1056) pg/mL on placebo and 375 (68–974) pg/mL on cilostazol (P = 0.006). In patients with PA pressure monitors, diastolic pressure was 20.5 (18.7–23.0) mmHg on placebo and 18.0 (17.0–20.0) mmHg on cilostazol, an effect linked to higher heart rates (P < 0.001).ConclusionsAmongst patients with HFpEF, short‐term treatment with cilostazol leads to improvements in health status and NT‐proBNP when compared with placebo. These effects are likely conveyed by a heart rate‐dependent reduction in cardiac filling pressures.Trial RegistrationClinicalTrials.gov Identifier: NCT05126836.

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Cilostazol for Secondary Stroke Prevention

Cited by 30 publications

References 94 publications

Our Efforts for Ideal Stroke Prevention and Treatment in Japan

Our Efforts for Ideal Stroke Prevention and Treatment in Japan

Long-Term Comparison of Cilostazol versus Clopidogrel in Secondary Prevention of Noncardioembolic Ischemic Stroke

Cilostazol in patients with heart failure and preserved ejection fraction—The CLIP‐HFpEF trial

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