(Circulation. 2001;103:2289.)
© 2001 American Heart Association, Inc.
Basic Science Reports |
Paclitaxel Stent Coating Inhibits Neointimal Hyperplasia at 4 Weeks in a Porcine Model of Coronary Restenosis
Presented in part at the 70th Scientific Sessions of the American Heart Association, Orlando, Fla, November 10–13, 1997, and published in abstract form (Circulation. 1997;96[suppl I]:I-288).
From the Division of Cardiology (A.W.H., G.M.J., B.S.A., K.E.B., J.A.B.) and Department of Pathology (R.H.H., B.R.), Johns Hopkins School of Medicine, and the National Institute on Aging, National Institutes of Health (L.C., P.F.H., D.-W.K., M.W., C.N., J.L.K., S.J.S., E.G.L., J.P.F.), Baltimore, Md; and Angiotech Pharmaceuticals, Inc, Vancouver, BC, Canada (W.L.H.).
Correspondence to Alan W. Heldman, MD, Division of Cardiology, Carnegie 565, Johns Hopkins Hospital, 600 N Wolfe St, Baltimore, MD 21287. E-mail aheldman{at}jhmi.edu
Background—Despite limiting elastic recoil and late vascular remodeling after angioplasty, coronary stents remain vulnerable to restenosis, caused primarily by neointimal hyperplasia. Paclitaxel, a microtubule-stabilizing drug, has been shown to inhibit vascular smooth muscle cell migration and proliferation contributing to neointimal hyperplasia. We tested whether paclitaxel-coated coronary stents are effective at preventing neointimal proliferation in a porcine model of restenosis.
Methods and Results—Palmaz-Schatz stents were dip-coated with paclitaxel (0, 0.2, 15, or 187 µg/stent) by immersion in ethanolic paclitaxel and evaporation of the solvent. Stents were deployed with mild oversizing in the left anterior descending coronary artery (LAD) of 41 minipigs. The treatment effect was assessed 4 weeks after stent implantation. The angiographic late loss index (mean luminal diameter) decreased with increasing paclitaxel dose (P<0.0028 by ANOVA), declining by 84.3% (from 0.352 to 0.055, P<0.05) at the highest level tested (187 µg/stent versus control). Accompanying this change, the neointimal area decreased (by 39.5%, high-dose versus control; P<0.05) with increasing dose (P<0.040 by ANOVA), whereas the luminal area increased (by 90.4%, high-dose versus control; P<0.05) with escalating dose (P<0.0004 by ANOVA). Inflammatory cells were seen infrequently, and there were no cases of aneurysm or thrombosis.
Conclusions—Paclitaxel-coated coronary stents produced a significant dose-dependent inhibition of neointimal hyperplasia and luminal encroachment in the pig LAD 28 days after implantation; later effects require further study. These results demonstrate the potential therapeutic benefit of paclitaxel-coated coronary stents in the prevention and treatment of human coronary restenosis.
Key Words: paclitaxel • stents • angioplasty • restenosis
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