Impact of Cilostazol on Restenosis After Percutaneous Coronary Balloon Angioplasty

Tsuchikane, Etsuo; Fukuhara, Atsunori; Kobayashi, Tohru; Kirino, Motohiro; Yamasaki, Kazuhiko; Kobayashi, Tomoko; Izumi, Mitsuru; Otsuji, Satoru; Tateyama, Hitone; Sakurai, Minoru; Awata, Nobuhisa

doi:10.1161/01.cir.100.1.21

Cited by 172 publications

(106 citation statements)

References 33 publications

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“…In addition, the release of platelet-derived growth factors may contribute to smooth muscle cell chemoattraction (into the intima) and proliferation (7). The relevance of these mechanisms to the actual occurrence of stent restenosis has been strongly questioned because clinical trials have failed to document any efficacy of antiplatelets and anticoagulants in preventing restenosis (8,9). DES reduce intimal hyperplasia and restenosis, but they also inhibit stent re-endothelization, making the vessel surface more thrombogenic for longer time periods.…”

Section: Discussionmentioning

confidence: 99%

Early restenosis after drug-eluting stent implantation: A putative role for platelet activation

Tamburino

Zimarino

Galassi

et al. 2007

Canadian Journal of Cardiology

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D rug-eluting stents (DES) are coated with antiproliferative agents that reduce neointimal formation (1) and substantially reduce restenosis compared with bare metal stents (2,3). However, the eluted drug inhibits stent endothelization, potentially rendering the inner stent surface more thrombogenic, and raises concern about a higher risk of stent thrombosis (4).In the present report, the occurrence of in-stent restenosis is documented in two patients after DES deployment at exactly the same sites where subacute stent thrombosis had occurred. CASE PRESENTATIONSCase 1 A 65-year-old man was admitted for effort angina three years after bypass surgery with the left internal mammary artery to the left anterior descending coronary artery (LAD), as well as a single saphenous vein graft sequentially anastomosed to the first diagonal, and first and second obtuse marginal (OM) branches. Coronary angiography documented the patency of the vein graft and the occlusion of the mammary artery graft. The LAD appeared diffusely diseased ( Figure 1A), and a percutaneous coronary intervention (PCI) was therefore performed, with two overlapping sirolimus-eluting stents (Cypher, Cordis, USA) successfully deployed at 1620 kPa ( Figure 1B). Dual antiplatelet therapy with acetylsalicylic acid (160 mg/day) and clopidogrel (300 mg bolus, followed by 75 mg/day) was recommended and initiated. One week after the procedure, the patient experienced angina at rest, and a repeat angiography showed two nonocclusive thrombi inside the distal stent in the LAD ( Figure 1C), with Thrombolysis In Myocardial Infarction (TIMI) grade 3 flow. An infusion of abciximab (ReoPro, Centocor, USA) was initiated (0.25 mg/kg bolus over 3 min, followed by a 12 h infusion at 0.125 μg/kg/min); balloon PCI was then successfully performed. Three months later, the patient had a recurrence of symptoms, and a third angiography showed two focal in-stent restenoses located at exactly the same sites of the previous thrombi inside the LAD ( Figure 1D). Intravascular ultrasound examination identified adequate stent expansion ( Figure 1E-F). The patient underwent a repeat successful balloon PCI, and 12-month dual antiplatelet therapy was recommended. Nine months later, angiography showed full stent patency. Case 2A 72-year-old diabetic hypertensive woman with a previous lateral myocardial infarction underwent coronary angiography for effort angina. Diffuse, severe disease of the LAD was documented ( Figure 2A), with a chronic occlusion of the distal left circumflex artery and an 80% ostial narrowing of the first OM branch. A staged PCI was planned, and acetylsalicylic acid (160 mg/day) and clopidogrel (75 mg/day) were started one week before the intervention. Abciximab was given in the catheterization laboratory as a bolus of 0.25 mg/kg over 3 min, followed by a 12 h infusion of 0.125 μg/kg/min. After a 2.0 mm balloon predilation, four overlapping paclitaxel-eluting stents (Taxus, Boston Scientific, USA) were deployed. However, after stent positioning, two small thrombi were de...

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Section: Discussionmentioning

confidence: 99%

Early restenosis after drug-eluting stent implantation: A putative role for platelet activation

Tamburino

Zimarino

Galassi

et al. 2007

Canadian Journal of Cardiology

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“…29 -34 Although there is some evidence that controlling mural thrombus formation may decrease neointimal hyperplasia, [35][36][37] antiplatelet agents have not reliably resulted in reductions in restenosis rates in clinical trials. 29,30 Similarly, the systemic administration of corticosteroids aimed at controlling the inflammatory process has not shown decreased restenosis rates.…”

Section: Coated Stentsmentioning

confidence: 99%

Coated Stents for the Prevention of Restenosis: Part I

2002

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O ver the past decade, the use of endoluminal metallic stents has become common practice during percutaneous coronary intervention (PCI), especially after clinical trials showed evidence of decreased restenosis rates when compared with balloon angioplasty alone. [1][2][3] Although stents significantly reduce restenosis when compared with balloon angioplasty, restenosis rates in patients who receive stents are still 20% to 40% at 6 months. [1][2][3][4][5][6] Recently, the concept of using stents coated with agents that could potentially inhibit neointimal hyperplasia has emerged. These agents include biocompatible materials, anticoagulants, corticosteroids, and antimitotic agents. This 2-part article reviews animal studies, human observational studies, and results from randomized clinical trials investigating coated stents. Part I discusses the pathophysiology of in-stent restenosis, as well as animal studies investigating coated stents. Part II discusses human studies investigating coated stents. Pathophysiology of In-Stent RestenosisIn-stent restenosis is primarily due to neointimal hyperplasia. [7][8][9][10][11][12][13] Vessel injury by an angioplasty balloon or stent struts leads to the activation of platelets and mural thrombus formation. [13][14][15][16] The presence of vascular injury, mural thrombus, and a metallic foreign body activates circulating neutrophils and tissue macrophages. 12,13,17,18 These cellular elements release cytokines and growth factors that activate smooth muscle cells. 19 -23 Upregulation and expression of genes such as c-myc that regulate cell division ensues, leading to cell proliferation. 24,25 Production of matrix metalloproteinases is also upregulated, leading to remodeling of the extracellular matrix, and initiating smooth muscle cell migration. 26 -28 The end result of this cascade of events is the uncontrolled proliferation of smooth muscle cells around the vessel intima and the deposition of extracellular matrix material, which often lead to significant luminal narrowing 3 to 6 months after PCI (Figure 1). Coated StentsThe systemic administration of a variety of agents has not had a significant impact on post-PCI restenosis rates. 29 -34 Although there is some evidence that controlling mural thrombus formation may decrease neointimal hyperplasia, [35][36][37] antiplatelet agents have not reliably resulted in reductions in restenosis rates in clinical trials. 29,30 Similarly, the systemic administration of corticosteroids aimed at controlling the inflammatory process has not shown decreased restenosis rates. 31 The lack of effect of systemically administered agents may be due to inadequate drug concentrations at the site of stent insertion. The limited success of these agents in decreasing rates of in-stent restenosis, coupled with side effects, prompted the development of coated stents.Stent coatings can be divided into 2 categories, biocompatible materials and drug-eluting coatings (Table 1). Biocompatible materials currently under investigation are thought to be less th...

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“…Tsuchikane et al, with quantitative coronary arteriography (QCA), found significantly less restenosis (p < 0.001), as well as lower rates of target lesion revascularization, larger minimal luminal diameter, and lower percent diameter stenosis for cilostazol versus aspirin in 211 patients after successful PTCA. 26 Another clinical trial in-volving 300 patients randomized to aspirin and ticlopidine, or aspirin and cilostazol, found that cilostazol was as efficacious as the standard regimen in preventing stent thrombosis. 24 A trend toward specific increased drug-related events (e.g., neutropenia) was seen for ticlopidine but not for cilostazol.…”

Section: Introductionmentioning

confidence: 99%

Rationale and design of the randomized, multicenter, Cilostazol for restenosis (CREST) trial

Douglas

Weintraub

Holmes

2003

Clinical Cardiology

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Summary:Restenosis of a segment of diseased coronary artery following metallic stenting is a common clinical problem and a major limitation of the procedure. Systemic pharmacologic interventions to deal with this problem have met with little success. Several small studies suggest that cilostazol, a phosphodiesterase III inhibitor whose pharmacologic properties include antiplatelet, antithrombotic, and vasodilatory effects; a beneficial effect on serum lipids; and in vitro inhibition of smooth muscle cell proliferation, may help prevent platelet aggregation and impede the accumulation of new intimal tissue in the stented artery. The Cilostazol for RESTenosis (CREST) trial will aim to evaluate more definitively the ability of cilostazol to prevent restenosis following uncomplicated stent implantation for de novo coronary artery stenosis. In this randomized, double-blind, multicenter study, 700 patients will receive clopidogrel, aspirin, and either cilostazol or placebo after successful intracoronary stent implantation. The primary endpoint is minimal luminal diameter (MLD) of the first lesion stented after 6 months; secondary endpoints include MLD in all lesions, mean percent diameter stenosis, target lesion revascularization, and major angiographic endpoints. Safety endpoints are abnormal complete blood count and liver function tests at 1, 3, and 6 months. The trial has been initiated, and enrollment is anticipated to be concluded in 2003. Cilostazol has properties that may reduce or avert in-stent coronary restenosis. The CREST trial is a large, rigorously conducted trial that may corroborate the favorable effects of cilostazol on coronary stent restenosis suggested by earlier studies.

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Impact of Cilostazol on Restenosis After Percutaneous Coronary Balloon Angioplasty

Abstract: Cilostazol significantly reduces restenosis and target lesion revascularization rates after successful PTCA.

Cited by 172 publications

References 33 publications

Early restenosis after drug-eluting stent implantation: A putative role for platelet activation

Early restenosis after drug-eluting stent implantation: A putative role for platelet activation

Coated Stents for the Prevention of Restenosis: Part I

Rationale and design of the randomized, multicenter, Cilostazol for restenosis (CREST) trial

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