Dual antiplatelet therapy using cilostazol for secondary prevention in patients with high-risk ischaemic stroke in Japan: a multicentre, open-label, randomised controlled trial

Toyoda, Kazunori; Uchiyama, Shinichiro; Yamaguchi, Takenori; Easton, J. Donald; Kimura, Kazumi; Hoshino, Haruhiko; Sakai, Nobuyuki; Okada, Yasushi; Tanaka, Kortaro; Origasa, Hideki; Naritomi, Hiroaki; Houkin, Kiyohiro; Yamaguchi, Keiji; Isobe, Masanori; Minematsu, Kazuo; Goto, Shinya; Isomura, Tatsuya; Matsumoto, Masayasu; Terayama, Yasuo; Tomimoto, Hidekazu; Tominaga, Teiji; Yasuda, Satoshi; Kumagai, Naoya

doi:10.1016/s1474-4422(19)30148-6

Cited by 149 publications

(144 citation statements)

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“…Also, trials published in the subgroup data from 14 studies were used directly from the previous meta-analysis. The following items were assessed [1]: random sequence generation [2]; allocation concealment [3]; publication characteristics [4], countries included in the study [5], enrolled population [6], blinding of participants, investigators and outcome assessors [7]; sample size randomized within 72 h of ictus [8], treatment duration [9], intention to treat analysis [10], completeness of follow up where a < 20% loss to follow up rate led to less bias [11], efficacy and safety outcomes [12], incomplete outcome data [13]; selective outcome reporting;…”

Section: Data Extraction and Quality Assessmentmentioning

confidence: 99%

“…Recurrent stroke may occur in 10 to 20% of patients within 3 months after the first stroke, therefore secondary prevention of stroke is very important. To reduce this burden, antiplatelet therapy is a key component of the management of non-cardioembolic ischemic stroke and transient ischemic attack [5]. The AHA/ASA recommended antiplatelet agents over oral anticoagulation to reduce the risk of recurrent stroke and other cardiovascular events (class I); and selection of an antiplatelet agent individualized on the basis of patient risk factor profiles, cost, tolerance, relative known efficacy of the agents, and other clinical characteristics (class I).…”

Section: Introductionmentioning

confidence: 99%

“…It has an anti-platelet, vasodilatory and anti-inflammation effect [7]. A newer antiplatelet which has a comparable effect in reducing secondary ischemic stroke and when used as dual anti platelet therapy has similar risk for bleeding compared to Aspirin or Clopidogrel monotherapy [5].…”

Section: Introductionmentioning

confidence: 99%

“…Given that antiplatelet agents act through a range of mechanisms, including platelet inhibition of thromboxane A2 production, inhibition of cyclic adenosine 3′, 5′-monophosphate production, and inhibition of P2Y12 receptors, a combination of agents can produce more effective stroke prevention than single agents [5]. Dual antiplatelet therapy may provide synergistic effect of inhibiting different platelet pathways for its activation.…”

Section: Introductionmentioning

confidence: 99%

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RETRACTED ARTICLE: Dual versus mono antiplatelet therapy for acute non- cardio embolic ischemic stroke or transient ischemic attack, an efficacy and safety analysis - updated meta-analysis

Albay¹,

Leyson²,

Cheng³

2020

BMC Neurol

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Background: New evidence on the efficacy and safety of dual antiplatelet therapy for secondary stroke prevention have been realized in the recent years. An updated meta analysis was done to determine the effect of the various dual antiplatelets vs aspirin alone on recurrence rate of ischemic stroke, cardiovascular morbidity and mortality, and its safety profile as reported through major bleeding. Methods: PubMed, Cochrane and Science Direct data bases were utilized, RCTs evaluating dual antiplatelet vs mono antiplatelet therapy for acute ischemic stroke or transient ischemic attack within < 72 h from ictus were searched up to July 2019. Risk ratio at 95% confidence intervals were calculated to evaluate stroke recurrence, cardiac events and mortality, and major bleeding. Results: Sixteen randomized controlled trials with a population of 28, 032 patients were pooled into a metaanalysis. Dual antiplatelet therapy was significantly superior over mono antiplatelet therapy in the reduction of stroke (RR 0.75, 95% CI:0.68-0.83, p value< 0.00001) and composite events namely cardiovascular morbidity and mortality (0.73 95% CI: 0.65-0.82, p value < 0.00001), while bleeding events were noted to be not significant (1.22 95% CI: 0.87-1.70, p value = 0.25). Conclusion: In acute non-cardioembolic ischemic strokes or those who have suffered a transient ischemic attack, dual antiplatelet therapy was associated with efficacy in stroke recurrence and composite cardiac events, with a non-significant risk of major bleeding.

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Section: Data Extraction and Quality Assessmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

RETRACTED ARTICLE: Dual versus mono antiplatelet therapy for acute non- cardio embolic ischemic stroke or transient ischemic attack, an efficacy and safety analysis - updated meta-analysis

Albay¹,

Leyson²,

Cheng³

2020

BMC Neurol

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“…A randomized double-blind, placebocontrolled trial in Japan, the Cilostazol Stroke Prevention Study (CSPS), showed that cilostazol reduced the risk of recurrent stroke compared with placebo (Matsumoto, 2005), and the Cilostazol for Prevention of Secondary Stroke study (CSPS2) demonstrated that there was no significant difference in stroke prevention measures between cilostazol and aspirin, but cilostazol resulted in fewer hemorrhagic events than aspirin alone (Shinohara et al, 2010). Moreover, dual antiplatelet therapy with cilostazol and aspirin or clopidogrel can reduce the incidence of ischemic stroke recurrence and bleeding compared with aspirin or clopidogrel alone (Toyoda et al, 2019). In addition, in vivo experiment data has shown that cilostazol had a protective effect against hypertension-induced endothelial dysfunction (Oyama et al, 2011), and may reduce the risk of developing dementia (Tai et al, 2017;Saito et al, 2019).…”

Section: Clinical Symptoms and Treatment Of Cerebral Small Vessel Dismentioning

confidence: 99%

Clinical Features and Experimental Models of Cerebral Small Vessel Disease

Shindo

Ishikawa

Yuichiro

et al. 2020

Front. Aging Neurosci.

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Cerebral small vessel disease (SVD) refers to a group of disease conditions affecting the cerebral small vessels, which include the small arteries, arterioles, capillaries, and postcapillary venules in the brain. SVD is the primary cause of vascular cognitive impairment and gait disturbances in aged people. There are several types of SVD, though arteriolosclerosis, which is mainly associated with hypertension, aging, and diabetes mellitus, and cerebral amyloid angiopathy (CAA) comprise most SVD cases. The pathology of arteriolosclerosis-induced SVD is characterized by fibrinoid necrosis and lipohyalinosis, while CAA-associated SVD is characterized by progressive deposition of amyloid beta (Aβ) protein in the cerebral vessels. Brain magnetic resonance imaging (MRI) has been used for examination of SVD lesions; typical lesions are characterized by white matter hyperintensity, lacunar infarcts, enlargement of perivascular spaces (EPVS), microbleeds, cortical superficial siderosis (cSS), and cortical microinfarcts. The microvascular changes that occur in the small vessels are difficult to identify clearly; however, these consequent image findings can represent the SVD. There are two main strategies for prevention and treatment of SVD, i.e., pharmacotherapy and lifestyle modification. In this review, we discuss clinical features of SVD, experimental models replicating SVD, and treatments to further understand the pathological and clinical features of SVD.

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Update on Cilostazol: A Critical Review of Its Antithrombotic and Cardiovascular Actions and Its Clinical Applications

Manolis

Manolis²,

Melita

et al. 2021

The Journal of Clinical Pharma

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Cilostazol, a phosphodiesterase III inhibitor, has vasodilating and antiplatelet properties with a low rate of bleeding complications. It has been used over the past 25 years for improving intermittent claudication in patients with peripheral artery disease (PAD). Cilostazol also has demonstrated efficacy in patients undergoing percutaneous revascularization procedures for both PAD and coronary artery disease. In addition to its antithrombotic and vasodilating actions, cilostazol also inhibits vascular smooth muscle cell proliferation via phosphodiesterase III inhibition, thus mitigating restenosis. Accumulated evidence has shown that cilostazol, due to its "pleiotropic" effects, is a useful, albeit underutilized, agent for both coronary artery disease and PAD. It is also potentially useful after ischemic stroke and is an alternative in those who are allergic or intolerant to classical antithrombotic agents (eg, aspirin or clopidogrel). These issues are herein reviewed together with the pharmacology and pharmacodynamics of cilostazol. Large studies and meta-analyses are presented and evaluated. Current guidelines are also discussed, and the spectrum of cilostazol's actions and therapeutic applications are illustrated.

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Dual antiplatelet therapy using cilostazol for secondary prevention in patients with high-risk ischaemic stroke in Japan: a multicentre, open-label, randomised controlled trial

Cited by 149 publications

References 31 publications

RETRACTED ARTICLE: Dual versus mono antiplatelet therapy for acute non- cardio embolic ischemic stroke or transient ischemic attack, an efficacy and safety analysis - updated meta-analysis

RETRACTED ARTICLE: Dual versus mono antiplatelet therapy for acute non- cardio embolic ischemic stroke or transient ischemic attack, an efficacy and safety analysis - updated meta-analysis

Clinical Features and Experimental Models of Cerebral Small Vessel Disease

Update on Cilostazol: A Critical Review of Its Antithrombotic and Cardiovascular Actions and Its Clinical Applications

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