Restenosis in-stent

Horvath C, Welt FG, Nedelman M, Rao P, Rogers C. Targeting CCR2 or CD18 inhibits experimental in-stent restenosis in primates inhibitory potential depends on type of injury and leukocytes targeted. Circ Res 2002 90(4) 488 494. 

Rapamycin (sirolimus), a macrolide antibiotic, has been used recently in organ transplantation for its potent immunosuppressive actions by inhibiting both cytokine mediated and growth factor mediated proliferation of smooth muscle cells and lymphocytes [55, 56]. In the RAVEL trial of non-acute single vessel lesions, the Sirolimus-eluting stent was compared to bare metal stent (BMS) in a 1 1 fashion [57]. One-year major adverse cardiovascular events and 6 month neointimal proliferation as assessed by late luminal loss (-0.01 0.33 mm in Sirolimus stent versus 0.80 0.53 mm in BMS) were improved. The Sirolimus-eluting stent thus virtually eliminated in-stent restenosis with no evidence of edge effect, dissection, or in-stent thrombosis. 

Kereiakes D, Linnemeier TJ, Bairn DS, et al. Usefulness of stent length in predicting in-stent restenosis (the MULTI-LINK stent trials). Am J Cardiol 2000 86 336-341. 

Kornowski R, Hong MK, Tio FO, Bramwell O, Wu H, Leon MB. In-stent restenosis contributions of inflammatory responses and arterial injury to neointimal hyperplasia. J Am Coll Cardiol 1998 31 224-230. 

George J, Herz I, Goldstein E, Abashidze S, Deutch V, Finkelstein A, Michowitz Y, Miller H, Keren G. Number and adhesive properties of circulating endothelial progenitor cells in patients with in-stent restenosis. Arterioscler Thromb Vase Biol 2003 23 e57-60. 

Gene therapy offers new possibilities for the treatment of cardiovascular diseases. This area of research has focused mainly on the treatment of postangioplasty restenosis, in-stent restenosis, and vein graft thickening. First clinical trials have shown that vascular gene transfer to humans is generally safe and well tolerated. Even... 

The ERASER Investigators, Acute platelet inhibition with abcix-imab does not reduce in-stent restenosis (ERASER study). Circulation 1999 100 799,... 

Waksman R, Ajani AE, White RL, et al. Prolonged antiplatelet therapy to prevent late thrombosis after intracoronary gamma-radiation in patients with in-stent restenosis Washington Radiation for In-Stent Restenosis Trial plus 6 months of clopidogrel (WRIST PLUS). Circulation 2001 103 2332-2335. 

Kuchulakanti B Wolfram R, "lorguson R, et al. Bivalirudin compared with llb/llla inhibitors in patients with in-stent restenosis undergoing intracoronary brachytherapy. Cardiovasc Revasc Med 2005 6 154-159. 

Lange H, et al. Folate therapy and in-stent restenosis after coronary stenting. N Engl J Med 2004 350(26) 2673-2681. 

Hoffmann R, Mintz GS, Dussaillant GR, et al. Patterns and mechanisms of in-stent restenosis a serial intravascular ultrasound study. Circulation 1996 94 1247-1254. 

Acute vessel recoil, chronic remodeling, and intimal hyperplasia were the mechanisms involved in this process (1-4). However, after the introduction of stents in the daily practice during interventional procedures, intimal hyperplasia became the mechanism associated in the pathophysiology of in-stent restenosis (5-9). Therefore, its prevention should be related with therapies that inhibit smooth muscle cell proliferation. 

First, there was a consistent benefit in clinical and angiographic binary restenosis data. As we can see in Table 2, in-stent restenosis of the two pilot studies, which comprised only de novo lesions, angiographic restenosis was in only a single digit of restenosis, with a late loss of around 0.6 mm. All these numbers represent, compared to the average restenosis rate of control arm from the more recent DES trials, a reduction of 81 % of in-stent restenosis and a 42% reduction of late loss, and also represent a reduction of 90% of MACCE. 

A small pilot trial from Brazil reporting 6.6% of in-stent restenosis with 0.61 mm of late loss and with no target lesion revascularization or any major events after two years of follow-up (47) also confirmed these positive results. 

In patients with in-stent restenosis, the first pilot trial reported negative results in a small population of inpatients presenting restenosis after brachiterapy failure however, of note, in this population, even with DES therapy, they also had negative results, some of them, such as those reported by the Thorax Center, with high incidence of restenosis and stent thrombosis (29,48). 

Among these 76 patients, 109 bare-coronary stents were deployed in 103 de novo lesions in an equal number of major native epicardial vessels. Patients with in-stent restenosis, bifurcation lesions, vein graft lesions, lesion length of >0.20 mm, acute myocardial infarction in the previous 72 hours, poor left ventricular function (ejection fraction <35%), renal failure defined as creatinine concentration of >2 mg, or under immunosuppressive treatment were excluded from the study. 

RodriguezA, Fernandez Pereira C, Rodriguez Alemparte M. Oral rapamycin in the treatment of diffuse proliferative in-stent restenosis in a patient with small reference vessel. J Invas Cardiol 2003 15 515-518. 

Hausleiter J, Kastrati A, Mehilli J, et al. Randomized, double blind, placebo controlled trial of oral sirolimus for restenosis prevention in patients with in-stent restenosis. The oral sirolimus to inhibit recurrent in-stent stenosis trial (OSIRIS). Circulation 2004 I 10 790. 

Chaves AJ, Sousa AG, Mattos L, etal, Pilot study with an intensified oral sirolimus regimen for the prevention of in-stent restenosis in de novo lesions, Catheter Cardiovasc Interv 2005 66 535-540. 

Tanabe (140) (TAXUS 111) 2003 NIRx Translute Human coronary art (in-stent restenosis) Paclitaxel 1 xg/mm2 Bare Yes... 

Commeau (155) (ISR II study) 2005 BX Velocity Polyethyl methacrylate Human coronary art (In-stent restenosis) Sirolimus 1,4 xg/mm2 ... 

Rogers C, Groothuis A, Toegel G, et al. Paclitaxel release from inert polymer material-coated stents curtails coronary in-stent restenosis in pigs [abstr]. Circulation 2000 102(18) ll 1566. 

Hong MK, Komowski R, Bramwell O, et al. Paclitaxel-coated gianturco-roubin II (GR II) stents reduce neointimal hyperplasia in a porcine coronary in-stent restenosis model. Coron Artery Dis 2001 12(6)513-515. 

GrubeE, Gerckens U, Rowold S, et al. Inhibition of in-stent restenosis by a drug eluting polymer stent pilot trail with 18 month follow-up [abstr]. Circulation 2000 l02(l8) ll-554. 

Mehran R, Dangas G, Abizaid AS, et al. Angiographic patterns of in-stent restenosis classification and implications for longterm outcome. Circulation 1999 100( 18) 1872-1878. 

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