Stent thrombosis

For patients undergoing primary PCI, clopidogrel is administered as a 300-to 600-mg loading dose followed by a 75 mg/day maintenance dose, in combination with aspirin 325 mg once daily, to prevent subacute stent thrombosis and long-term cardiovascular events. 

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. 

The pivotal US trial for the Paclitaxel stent was the TAXUS IV trial, which enrolled 1,314 patients with single de novo coronary lesions (Length 10-28 mm and diameter 2.5-3.75 mm) [67] (Fig. 5.7). Target vessel revascularization based on ischemic symptoms was reduced from 12 to 4.7% p < 0.001). The rate of restenosis by angiography was considerable lower (7.9% versus 26.6% p < 0.001), with no difference in the rate of cardiac death, myocardial infarction, or stent thrombosis. 

In 2006, however, focus shifted to another rare but potentially catastrophic event known as late stent thrombosis, which, in contrast to subacute thrombosis, occurs months to years after stent placement. It usually occurs before endothelialization is complete. For bare metal stents, this takes a few weeks. However, in drug eluting stents, this process of endotheliazation is delayed [68]. This complication... 

Over the ensuing months, new criterion was proposed for defining stent-thrombosis in an attempt to establish uniformity, eliminate inappropriate censoring, and improve sensitivity. 

One of the significant factors promoting late stent thrombosis has been found to be premature discontinuation of dual antiplatelet therapy (aspirin and clopidrogel). In an analysis of 4,666 of patients undergoing initial PCI with BMS or DES, researchers from the Duke Heart center reported that longterm risk for death and major cardiac events was significantly increased among patients in the DES... 

Uren NG, Schwarzacher SP, Metz JA, et al. Predictors and outcomes of stent thrombosis an intrazvascular ultrasound registry. Eur Heart J 2002 23 124-132. 

Serruys PW, Daemen I. Are drug-eluting stents associated with a higher rate of late thrombosis than bare metal stents Late stent thrombosis a nuisance in both bare metal and drug-eluting stents. Circulation 2007 115 1433-1439. 

Mauri L, Hsieh WH, Massaro IM, et al. Stent thrombosis in randomized clinical trials of drug-eluting stents. N Engl J Med 2007 356 1020-1029. 

Lee S-W, Park S-W, Hong M-K, et al. Triple versus dual antiplatelet therapy after coronary stenting impact on stent thrombosis. J Am Coll Cardiol 2005 46 1833-1837. 

I 5 Gurbel PA, Bliden KR Samara W, et al. Clopidogrel effect on platelet reactivity in patients with stent thrombosis results of the CREST Study. J Am Coll Cardiol 2005 46 1827-1832. 

Ajzenberg N, Aubry R Huisse MG, et al. Enhanced shear-induced platelet aggregation in patients who experience subacute stent thrombosis a case-control study J Am Coll Cardiol 2005 45 1753-1756. 

Barragan R Bouvier JL, Roquebert PO, et al, Resistance to thienopyridines clinical detection of coronary stent thrombosis by monitoring of vasodilator-stimulated phosphoprotein phosphorylation. Catheter Cardiovasc Interv 2003 59 295-302. 

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). 

Rodriguez A, MieresJ, Fernandez-Pereira C, et al Coronary stent thrombosis in current drug eluting stent era insights from ERACI III trial. J Am Coll Cardiol 2006 47 205-207. 

Heparin-coated Palmaz-Schatz, Wiktor, Jostent, BX Velocity, and beStent have been investigated in clinical studies. All studies showed that heparin-coated stents are safe, even in high-risk lesions. When compared with balloon angioplasty, heparin-coated stents could significantly reduce the rate of subacute stent thrombosis and the late restenosis. However, no significant difference of restenosis was observed between the heparin-coated stent and the bare stent control. 

Sheth S, Dev V Jacobs H, et al. Prevention of subacute stent thrombosis by polymer-polyethylene oxide-heparin coating in rabbit carotid artery [abstr]. J Am Coll Cardiol 1995 25 348A. 

Wohrle J, Grotzinger U, Al-Kayer I, et al. Comparison of the heparin-coated and the uncoated version of the JOMED stent with regards to stent thrombosis and restenosis rates [abstr], Eur Heart J I 999 20(suppl) 27l. 

Gupta V Aravamuthan BR, Baskerville S, et al, Reduction of subacute stent thrombosis (SAT) using heparin-coated stents in a large-scale, real world registry. J Invasive Cardiol 2004 ... 

Mitchel JF McKay RG, Treatment of acute stent thrombosis with local urokinase therapy using catheter-based, drug delivery systems a case report. Cathet Cardiovasc Diagn 1995 34(2) 149-154. 

In addition, attempts to deliver radiation therapy to symptomatic de novo or restenotic native coronary-artery lesions included the deployment of very low activity 32P radioactive stents. Preliminary data for clinical endpoints (e.g., subacute stent thrombosis, TLR, and death at 30 days) appeared promising, but the long-term angiographic follow-up revealed an unacceptable restenosis rate at or beyond the stent edges (21,22). Consequently, further studies to evaluate this technique were abandoned. 

The one-month farm swine studies evaluated safety following implantation of two doses of batimastat loaded on the 18 mm BiodivYsio stent in comparison to control stent without batimastat. Two batimastat doses were evaluated as described in Table 2. No deaths occurred during the implantation procedure and no sub-acute death or stent thrombosis was observed during the follow-up period. Histological examination confirmed that all the vessels were patent, without the presence of thrombus in the vessel lumen, All sections showed stent struts to be completely covered, leading to a smooth endoluminal surface. There was no excessive inflammatory response at stent struts in BiodivYsio-Batimastat-treated sections compared with the control sections. Medial and adventitial layers appeared similar in all three groups. The perivascular nerve fibers, the adipose tissue, and adjacent myocardium appeared normal in control and Biod/VV s/o-Batimastat-treated sections. Therefore, these studies demonstrated that the Biod/VY s/o Batimastat stent at CTD and >CTD was well tolerated up to 28 days. 

PTCA). The primary objective was to evaluate the occurrence of major adverse cardiac events (MACE) [death, recurrent myocardial infarction (Ml), or clinically driven target lesion revascularization] 30 days postprocedure. The secondary objectives were to evaluate the binary restenosis, incidence of (sub)acute stent thrombosis at 30 days follow-up, MACE at 6 and 12 months and the QCA endpoints at 6 months. This study was designed to allow a comparison with the patient population and the results of a larger randomized DISTINCT (BiodivYsio stent in controlled clinical trial) study previously conducted in the U.S. 

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