Spotlight on the sirolimus-eluting stent in coronary artery disease
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The sirolimus-eluting stent (CYPHER™) is a metal stent coated with 140 μg/cm2 of sirolimus blended with synthetic polymers. After stent implantation, sirolimus is slowly released causing localized cytostatic inhibition of proliferation of vascular smooth muscle cells in the peri-stent arterial wall over a period of about 1 month. Only minimal amounts of sirolimus enter the bloodstream and these appear to be insufficient to be of clinical relevance.
In clinical trials that evaluated single de novo lesions and in-stent restenosis in patients with coronary artery disease, the sirolimus-eluting stent was associated with minimal neointimal hyperplasia. In four randomized trials in de novo lesions, sirolimus eluting stents produced a significantly lower incidence of major adverse cardiac events (MACE) than that observed in patients with uncoated stents, during periods of up to 2 years (p < 0.05 for all comparisons). The lower incidence of MACE was mostly due to a reduced requirement for repeat target vessel revascularization. At angiographic follow-up at periods of up to 8 months, late luminal loss was significantly smaller in the sirolimus-eluting stent groups than in the uncoated-stent groups (p < 0.001 in all studies).
The sirolimus-eluting stent was well tolerated in clinical trials of up to 3 years’ follow-up. Because minimal blood levels of sirolimus are achieved, systemic adverse effects appear to be avoided. To date, there has been no evidence of any potential adverse effects resulting from the polymer coating or local drug toxicity. As yet, there is no evidence of an increased risk of subacute or late thrombosis, or aneurysm formation with the sirolimus-eluting stent compared with the uncoated stent. Long-term follow-up is needed to fully assess these theoretical concerns. Cost-effectiveness analyses over 12 months demonstrated a cost advantage for the sirolimus-eluting stent compared with an uncoated stent because of a reduced requirement for repeat target vessel revascularizations.
Conclusion: Initial clinical trials with the sirolimus-eluting stent in patients with de novo coronary lesions have shown a significantly reduced incidence of MACE and of restenosis compared with a standard stent. Efficacy appears to be maintained throughout follow-up periods of up to 2 years in randomized trials, and to date, systemic or local adverse effects have been avoided. If efficacy and tolerability are consistently demonstrated over the long term, the sirolimus-eluting stent will be a major advance in the control of in-stent restenosis.
KeywordsSirolimus Stent Implantation Major Adverse Cardiac Event Late Thrombosis Late Luminal Loss
The full text in The American Journal of Cardiovascular Drugs 2003: 3 (3): 211–230 was reviewed by: A. Bakhai, Interventional Cardiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA; A. Colombo, Cardiac Catheterization Laboratory, EMO Centro Curore Columbus, Milano, Italy; J.-M. Juliard, Interventional Cardiology Department, Bichat Hospital, Paris, France; T. Lefévre, Institut Hospitalier Jacques Cartier, Massy, France; A.M. Lincoff, Department of Cardiovascular Medicine, The Cleveland Clinic Foundation, Cleveland, Ohio, USA; J.W. Moses, Lenox Hill Heart and Vascular Institute and Cardiovascular Research Foundation, New York, New York, USA; R. Wilensky, Experimental Interventional Cardiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
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