Stents sirolimus

Zotarolimus (53 Endeavor stent) Sirolimus (33) Macrolide antibiotic Semi-synthetic NP Microbial Cardiovascular surgery Inhibits cell proliferation, preventing scar tissue formation and minimizes restenosis in angioplasty patients 467 74... 

Coronary stents Sirolimus (impregnated stent) Good... 

Parry TJ, Brosius R, Thyagarajan R, et al. Drug-eluting stents sirolimus and paclitaxel differentially affect cultured cells and injured arteries. EurJ Pharm 2005 524(1-3)4 9-29. 

The introduction of drug-eluting stents, Sirolimus-Eluting, may solve the problem of in-stent restenosis in LEAD fi 7) a gratifying experience similar to that with drug (rapamycine or taxol) eluting stents for coronary lesions. 

At least 2 to 3 months for sirolimus-eluting stent placement. 

Percutaneous coronary intervention A minimally invasive procedure whereby access to the coronary arteries is obtained through the femoral artery up the aorta to the coronary os. Contrast media is used to visualize the coronary artery stenosis using a coronary angiogram. A guidewire is used to cross the stenosis and a small balloon is inflated and/or stent is deployed to break up atherosclerotic plaque and restore coronary artery blood flow. The stent is left in place to prevent acute closure and restenosis of the coronary artery. Newer stents are coated with antiproliferative drugs, such as paclitaxel and sirolimus, which further reduce the risk of restenosis of the coronary artery. 

For patients undergoing PCI and receiving stents, the recommended dose is 325 once daily for at least 30 days with bare metal stents, for 3 months with a sirolimus-eluting stent, and for 6 months with a paclitaxel-eluting stent, followed by 75 to 162 mg once daily thereafter. 

According to ACC/AHA 2007 guidelines, clopidogrel is indicated for up to 12 months in NSTE ACS patients, with a minimum treatment duration of 1 month after placement of a bare-metal stent and 12 months after placement of a sirolimus- or paclitaxel-coated stent. 

Morice MC, Serruys PW, Sousa JE, et al. A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization. N Engl J Med 2002 346 1773-1780. 

Zotarohmus (53 EndeavorT stent ABT-578 Medtronic, 2005), a semisynthetic derivative of sirolimus (34), was designed for use in stents with phosphorylcholine as a carrier coronary stents reduce early complications... 

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. 

In a subset of RAVEL, three-dimensional IVLfS was used to characterize post-stent characteristics at 6 months [58]. Binary re-stenosis and late angiographic loss with the sirolimus stent was again eliminated at 6 months compared to the BMS (0% and 0.06 0.30 mm versus 23.4% and 0.91 0.58 mm) despite having a 21% incidence of incomplete stent apposition at 6 months compared to only 4% in the standard stent. While other trials have demonstrated... 

Another sirolimus analogue, Everolimus, on cobalt chromium stent platform (XIENCE V stent, Abbott Laboratories, Abbott Park, Illinois), was compared to the TAXUS stent in the SPIRIT III trial and found to have better MACE rates. The XIENCE V is approved in Europe and is awaiting FDA approval. 

Holmes DR Jr, Leon MB, Moses JW, Popma JJ, Cutlip D, Fitzgerald PI, Brown C, Fischell T, Wong SC, Midei M, Snead D, Kuntz RE. Analysis of 1-year clinical outcomes in the SIRIUS trial a randomized trial of a sirolimus-eluting stent versus a standard stent in patients at high risk for coronary restenosis. Circulation. 2004 Feb 10 109(5) 634-40. 

Moses J, Leon M, Popma J, et al. Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. N Engl J Med 2003 349 1315-1323. 

Sirolimus has also been used in the production of sirolimus-eluting stents. These stents are used to treat obstructive coronary arteries. The rationale for the use of sirolimus in these stents is due to its antiproliferative activity. It has also received attention for cancer treatment due to its antiproliferative effects. In animal studies, sirolimus has shown some potential in the treatment of cancer where in combination with doxorubicin, a remission for Akt-positive lymphomas has been observed. 

To provide optimal immunosuppressant effects, sirolimus is typically combined with glucocorticoids or other immunosuppressants. Sirolimus exerts a number of other beneficial effects, including the ability to inhibit smooth muscle proliferation in blood vessel walls. For this reason, sirolimus is sometimes incorporated into drug-eluting stents that is, a supportive tubular structure (stent) is placed in the lumen of a partially occluded artery, and the drug is released slowly from the stent to help reduce vessel occlusion.64... 

Schluter M, Schofer J. Direct stenting with sirolimus-eluting stents. Am Heart HospJ. 2005 3 182-186, 192. 

Kotani J, Awata M, Nanto S, et al. Incomplete neointimal coverage of sirolimus-eluting stents Angioscopic findings. J Am Coll Cardiol 2006 47 2108-2111. 

Recent studies have demonstrated evidence for coronary endothelial dysfunction after drug-eluting stenting, logni et al. (77) studied coronary endothelial function in 25 patients six months after stent deployment and found paradoxic exercise-induced vasoconstriction in coronary segments adjacent to sirolimus-eluting stents, but vasodilation in patients with bare-metal stents. Similarly, Hofma et al. (78) noted a pronounced... 

Togni M, Windecker S, Cocchia R, et al, Sirolimus-eluting stents associated with paradoxic coronary vasoconstriction. J Am Coll Cardiol 2005 46 23 1-236. 

Hofma SH, van der Giessen WJ, van Dalen BM, et al. Indication of long-term endothelial dysfunction after sirolimus-eluting stent implantation. Eur Heart J 2006 27 166-170. 

Brito et at, in a pilot study, tested the hypothesis that oral sirolimus is safe and effective to inhibit in-stent NIH and, therefore, effective to prevent and treat ISR. Twelve patients (18 lesions) with high risk for ISR, including eight ISR lesions, were incorporated. One day before the procedure, patients were given a 15 mg loading dose of oral sirolimus, followed by 5 mg daily for 28 days, with weekly whole blood level measurements. The four- and eight-month follow-up revealed an angiographic late loss of 0.40 0.24 and 0.67 0.45 mm (P < 0.01), respectively. At 24-month clinical follow-up, adverse events were one death (8.3%), two TLR (I I. I %), and four TVR (22.2%) (33). 

Brito FSJr, Rosa WC, ArrudaJA, Tedesco H, PestanaJO, Lima VC. Efficacy and safety of oral sirolimus to inhibit in-stent inti-mal hyperplasia. Catheter Cardiovasc Interv 2005 64 413-418. 

Between September 2003 and September 2004, 100 patients were randomized, 50 patients in control (55 arteries and 59 lesions) and 50 patients in oral sirolimus arm (60 arteries and 66 lesions). A total of 132 stents were deployed, 61 in control and 71 in oral sirolimus small-stent sizes (2.5 mm) were deployed in 44.7% of the lesions. 

SousaJE, Costa MA, Abizaid AC, et al, Sustained suppression of neointimal proliferation by sirolimus-eluting stents. One-year angiographic and intravascular ultrasound follow-up. Circulation. 2001 104 2007-201 I. 

Schampaert E, Cohen EA, Schluter M, et al. The Canadian study of the sirolimus-eluting stent in the treatment of patients with long de novo lesions in small native coronary arteries (C-SIRIUS). J Am Coll Cardiol 2004 43 1 I 10-1 I 15. 

Schofer J, Schluter M, Gershlick AH, et al. Sirolimus-eluting stents for treatment of patients with long atherosclerotic lesions in small coronary arteries. Double-blind, randomized controlled trial. (E-SIRIUS). Lancet 2003 362 1093-1099. 

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