Comparison of Ticlopidine and Cilostazol for the Prevention of Restenosis after Percutaneous Transluminal Coronary Angioplasty.

Nagaoka, Noriyasu; Okazaki, Katsuo; Masuda, Naomichi; Shikaura, Kyoko; Hotta, Nigishi

doi:10.1536/jhj.42.43

Cited by 12 publications

(10 citation statements)

References 30 publications

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“…Small-scale clinical trials of thienopyridine compounds have hinted at their ability to reduce restenosis after PCI 26 ; however, no adequately powered, randomized controlled trials to date have examined the effects of clopidogrel on restenosis. The Clopidogrel for Reduction of Events During Observation (CREDO) study 27 compared the strategies of starting clopidogrel either before or after PCI but was not powered or designed to assess the impact of an effective loading regimen of clopidogrel on restenosis.…”

Section: Discussionmentioning

confidence: 99%

Platelet P2Y ₁₂ Receptor Influences the Vessel Wall Response to Arterial Injury and Thrombosis

et al. 2009

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Background-Platelets are believed to play an important role in atherogenesis and the vessel response to vascular injury.The P2Y 12 receptor (P2Y 12 ) plays a central role in amplifying platelet aggregation, dense granule and ␣-granule secretion, P-selectin expression, microparticle formation, and procoagulant membrane changes, regardless of the activating stimulus. We hypothesized that P2Y 12 deficiency might reduce the vessel wall response to vascular injury as well as thrombosis in murine vascular injury models. Methods and Results-P2Y 12 -deficient (Ϫ/Ϫ) mice and littermate controls (ϩ/ϩ) were bred on a C57 BL/6 background.In vivo murine models of arterial injury were employed alone and in combination with bone marrow transplantation to investigate the role of P2Y 12 in the vessel wall response to arterial injury and thrombosis. At 21 days after ferric chloride injury, neointima formation in P2Y 12 Ϫ/Ϫ arteries was significantly less than that observed in control strain arteries (PϽ0.025). In agreement with this, the intima-media ratio was significantly greater in femoral wire-injured arteries from P2Y 12 ϩ/ϩ compared with P2Y 12 Ϫ/Ϫ animals (PϽ0.05). Bone marrow transplantation was used to examine the importance of vessel wall P2Y 12 versus platelet P2Y 12 . Analysis of arterial sections from chimeric animals at 21 days after injury revealed a smaller intima-media ratio in Ϫ/Ϫ to ϩ/ϩ animals than in the positive (ϩ/ϩ to ϩ/ϩ) control group (PϽ0.01).Conclusions-These data demonstrate a role for platelet P2Y 12 in the vessel wall response to arterial injury and thrombosis.This illustrates the manner in which platelets may contribute to atherogenesis and restenosis. Key Words: arterial thrombosis Ⅲ platelets Ⅲ restenosis Ⅲ muscle, smooth A ccumulating evidence supports important roles for the platelet in atherogenesis and restenosis after percutaneous coronary intervention (PCI). Vessel injury and atherogenesis can result in luminal exposure of thrombogenic subendothelial components such as tissue factor and von Willebrand factor, resulting in platelet degranulation and release of several platelet activators, including ADP. The ensuing platelet activation, adhesion, and aggregation are considered the initial steps in thrombus formation. [1][2][3] Once recruited to or in the proximity of the vessel wall, platelets may release or express a plethora of proinflammatory molecules, including platelet factor 4, macrophage inflammatory protein 1-␣, Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES), CD40 ligand, interleukin-1, transforming growth factor-␤, and P-selectin. 4 -8 Two Gprotein-coupled receptors for ADP exist on platelets, P2Y 1 and P2Y 12 . 9 -11 ADP-induced platelet aggregation is initiated by the P2Y 1 receptor and amplified and sustained in a synergistic manner by the P2Y 12 receptor. The P2Y 12 receptor also amplifies platelet aggregation induced by other agonists such as thrombin and consequently plays an important role in thrombogenesis and thrombus stability. 12-14 P2Y 12 receptor...

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Section: Discussionmentioning

confidence: 99%

Platelet P2Y ₁₂ Receptor Influences the Vessel Wall Response to Arterial Injury and Thrombosis

et al. 2009

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“…According to the inclusion criteria, 12 randomized controlled trials were included in this meta-analysis (3–5,8,14,19–25). The publication year of the included studies ranged from 1999 to 2006.…”

Section: Resultsmentioning

confidence: 99%

“…Ticlopidine is a potent inhibitor of collagen-induced platelet aggregation, which has been demonstrated to decrease the incidence of clinical events following coronary stenting (14). By activating platelet adenylate cyclase, ticlopidine is able to enhance the stimulatory action of prostaglandin E1 (PGE1) on the cyclase and block the inhibitory action of PGE2 on the cyclase (5). However, compared with cilostazol, the use of ticlopidine may result in more severe side-effects, therefore leading to a shorter course of treatment (29).…”

Section: Discussionmentioning

confidence: 99%

“…Although coronary stenting is widely used in the treatment of patients with CHD, the high rates of late restenosis and stent thrombosis remain the primary limitations (3). At present, adjunctive antiplatelet therapy has been suggested to reduce the incidence rate of restenosis and stent thrombosis (4,5). In addition, the utilization of antiplatelet agents has been demonstrated to be effective in improving final outcomes (6).…”

Section: Introductionmentioning

confidence: 99%

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Comparison of cilostazol versus ticlopidine following coronary stenting in patients with coronary heart disease: A meta-analysis of randomized controlled trials

Yang

et al. 2013

Experimental and Therapeutic Medicine

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Previous studies have shown that the combination of cilostazol and aspirin may be a more effective regimen than ticlopidine plus aspirin in the prevention of late restenosis and acute or subacute stent thrombosis following coronary stenting; however, individually published results are inconclusive. The aim of this meta-analysis was to compare the differences in late restenosis and stent thrombosis between cilostazol plus aspirin and ticlopidine plus aspirin for patients with coronary heart disease (CHD) following coronary stenting. A literature search of Pubmed, Embase, Web of Science and Chinese BioMedicine (CBM) databases was conducted from 1998 to March 1, 2013 and statistical analysis was performed using Stata statistical software, version 12.0. Twelve randomized controlled trials were included in the study, with a total of 2,708 patients with CHD following coronary stenting. The patient population comprised 1,371 patients treated with cilostazol plus aspirin and 1,337 patients treated with ticlopidine plus aspirin. The meta-analysis showed that cilostazol plus aspirin demonstrated a lower rate of restenosis than ticlopidine plus aspirin [odds ratio (OR)=0.83, 95% confidence interval (CI)=0.69–0.99, P=0.047]. A significant difference was also observed in the average percent diameter stenosis between cilostazol plus aspirin and ticlopidine plus aspirin [standardized weight difference (SMD)= −0.57, 95% CI=−0.92, −0.23, P=0.001). However, there were no significant differences in the rates of acute or subacute stent thrombosis between cilostazol plus aspirin and ticlopidine plus aspirin. The present meta-analysis suggests that cilostazol plus aspirin may result in a lower restenosis rate and percent diameter stenosis than ticlopidine plus aspirin for patients with CHD following coronary stenting.

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“…Thus, antiplatelet agents were studied early in the history of this model as a potential therapy (32,33) and showed efficacy in reducing neointimal thickness. A wide variety of other agents have been studied in this model and are discussed later.…”

Section: Animal Restenosis Models: a Brief Overviewmentioning

confidence: 99%

Preclinical restenosis models and drug-eluting stents

Schwartz

Chronos²,

Virmani

2004

Journal of the American College of Cardiology

118

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Percutaneous coronary intervention continues to revolutionize the treatment of coronary atherosclerosis. Restenosis remains a significant problem but may at last be yielding to technologic advances. The examination of neointimal hyperplasia in injured animal artery models has helped in our understanding of angioplasty and stenting mechanisms, and as drug-eluting stent (DES) technologies have arrived, they too have been advanced through the study of animal models. These models are useful for predicting adverse clinical outcomes in patients with DESs because suboptimal animal model studies typically lead to problematic human trials. Similarly, stent thrombosis in animal models suggests stent thrombogenicity in human patients. Equivocal animal model results at six or nine months occasionally have been mirrored by excellent clinical outcomes in patients. The causes of such disparities are unclear but may result from differing methods, including less injury severity than originally described in the models. Ongoing research into animal models will reconcile apparent differences with clinical trials and advance our understanding of how to apply animal models to clinical stenting in the era of DESs.

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Comparison of Ticlopidine and Cilostazol for the Prevention of Restenosis after Percutaneous Transluminal Coronary Angioplasty.

Cited by 12 publications

References 30 publications

Platelet P2Y ₁₂ Receptor Influences the Vessel Wall Response to Arterial Injury and Thrombosis

Platelet P2Y ₁₂ Receptor Influences the Vessel Wall Response to Arterial Injury and Thrombosis

Comparison of cilostazol versus ticlopidine following coronary stenting in patients with coronary heart disease: A meta-analysis of randomized controlled trials

Preclinical restenosis models and drug-eluting stents

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Comparison of Ticlopidine and Cilostazol for the Prevention of Restenosis after Percutaneous Transluminal Coronary Angioplasty.

Cited by 12 publications

References 30 publications

Platelet P2Y 12 Receptor Influences the Vessel Wall Response to Arterial Injury and Thrombosis

Platelet P2Y 12 Receptor Influences the Vessel Wall Response to Arterial Injury and Thrombosis

Comparison of cilostazol versus ticlopidine following coronary stenting in patients with coronary heart disease: A meta-analysis of randomized controlled trials

Preclinical restenosis models and drug-eluting stents

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Product

Resources

About

Platelet P2Y ₁₂ Receptor Influences the Vessel Wall Response to Arterial Injury and Thrombosis

Platelet P2Y ₁₂ Receptor Influences the Vessel Wall Response to Arterial Injury and Thrombosis