A polymer-based, paclitaxel-eluting stent in patients with coronary artery disease.

BACKGROUND Restenosis after coronary stenting necessitates repeated percutaneous or surgical revascularization procedures. The delivery of paclitaxel to the site of vascular injury may reduce the incidence of neointimal hyperplasia and restenosis. METHODS At 73 U.S. centers, we enrolled 1314 patients who were receiving a stent in a single, previously untreated coronary-artery stenosis (vessel diameter, 2.5 to 3.75 mm; lesion length, 10 to 28 mm) in a prospective, randomized, double-blind study. A total of 652 patients were randomly assigned to receive a bare-metal stent, and 662 to receive an identical-appearing, slow-release, polymer-based, paclitaxel-eluting stent. Angiographic follow-up was prespecified at nine months in 732 patients. RESULTS In terms of base-line characteristics, the two groups were well matched. Diabetes mellitus was present in 24.2 percent of patients; the mean reference-vessel diameter was 2.75 mm, and the mean lesion length was 13.4 mm. A mean of 1.08 stents (length, 21.8 mm) were implanted per patient. The rate of ischemia-driven target-vessel revascularization at nine months was reduced from 12.0 percent with the implantation of a bare-metal stent to 4.7 percent with the implantation of a paclitaxel-eluting stent (relative risk, 0.39; 95 percent confidence interval, 0.26 to 0.59; P<0.001). Target-lesion revascularization was required in 3.0 percent of the group that received a paclitaxel-eluting stent, as compared with 11.3 percent of the group that received a bare-metal stent (relative risk, 0.27; 95 percent confidence interval, 0.16 to 0.43; P<0.001). The rate of angiographic restenosis was reduced from 26.6 percent to 7.9 percent with the paclitaxel-eluting stent (relative risk, 0.30; 95 percent confidence interval, 0.19 to 0.46; P<0.001). The nine-month composite rates of death from cardiac causes or myocardial infarction (4.7 percent and 4.3 percent, respectively) and stent thrombosis (0.6 percent and 0.8 percent, respectively) were similar in the group that received a paclitaxel-eluting stent and the group that received a bare-metal stent. CONCLUSIONS As compared with bare-metal stents, the slow-release, polymer-based, paclitaxel-eluting stent is safe and markedly reduces the rates of clinical and angiographic restenosis at nine months.

[1]  Jeffrey W Moses,et al.  Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. , 2003, The New England journal of medicine.

[2]  S. Silber,et al.  Randomized Study to Assess the Effectiveness of Slow- and Moderate-Release Polymer-Based Paclitaxel-Eluting Stents for Coronary Artery Lesions , 2003, Circulation.

[3]  Mary E. Russell,et al.  TAXUS I: Six- and Twelve-Month Results From a Randomized, Double-Blind Trial on a Slow-Release Paclitaxel-Eluting Stent for De Novo Coronary Lesions , 2003, Circulation.

[4]  M. Eisenberg,et al.  Coated stents for the prevention of restenosis: Part I. , 2002, Circulation.

[5]  Eric J Topol,et al.  Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. , 2002, JAMA.

[6]  P. Serruys,et al.  A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization. , 2002, The New England journal of medicine.

[7]  C. Morillo,et al.  Clinical and quantitative coronary angiographic predictors of coronary restenosis: a comparative analysis from the balloon-to-stent era. , 2001, Journal of the American College of Cardiology.

[8]  R. Virmani,et al.  Pathological Analysis of Local Delivery of Paclitaxel Via a Polymer-Coated Stent , 2001, Circulation.

[9]  T. Fojo,et al.  Low concentrations of paclitaxel induce cell type-dependent p53, p21 and G1/G2 arrest instead of mitotic arrest: molecular determinants of paclitaxel-induced cytotoxicity , 2001, Oncogene.

[10]  A. Küttner,et al.  Inhibition of smooth muscle cell proliferation after local drug delivery of the antimitotic drug paclitaxel using a porous balloon catheter , 2001, Basic Research in Cardiology.

[11]  B. McManus,et al.  Complete inhibition of intimal hyperplasia by perivascular delivery of paclitaxel in balloon-injured rat carotid arteries. , 2001, Journal of vascular and interventional radiology : JVIR.

[12]  G. Mintz,et al.  Coronary in-stent restenosis - predictors, treatment and prevention. , 2000, European heart journal.

[13]  J. Testa,et al.  The phosphatidylinositol 3-kinase/AKT signal transduction pathway plays a critical role in the expression of p21WAF1/CIP1/SDI1 induced by cisplatin and paclitaxel. , 2000, Cancer research.

[14]  A. Baumbach,et al.  Local paclitaxel delivery for the prevention of restenosis: biological effects and efficacy in vivo. , 2000, Journal of the American College of Cardiology.

[15]  G. Stone,et al.  Angiographic patterns of in-stent restenosis: classification and implications for long-term outcome. , 1999, Circulation.

[16]  E. DeLong,et al.  Acute and long-term cost implications of coronary stenting. , 1999, Journal of the American College of Cardiology.

[17]  R. Virmani,et al.  Pathology of acute and chronic coronary stenting in humans. , 1999, Circulation.

[18]  J. Tobis,et al.  Angiographic and intravascular ultrasound predictors of in-stent restenosis. , 1998, Journal of the American College of Cardiology.

[19]  T. Cruz,et al.  Inhibition of activator protein 1 activity by paclitaxel suppresses interleukin-1-induced collagenase and stromelysin expression by bovine chondrocytes. , 1998, Arthritis and rheumatism.

[20]  T. Fojo,et al.  Microtubule-interfering Agents Activate c-Jun N-terminal Kinase/Stress-activated Protein Kinase through Both Ras and Apoptosis Signal-regulating Kinase Pathways* , 1998, The Journal of Biological Chemistry.

[21]  M. Hadamitzky,et al.  Predictive factors of restenosis after coronary stent placement. , 1997, Journal of the American College of Cardiology.

[22]  A. Küttner,et al.  Paclitaxel inhibits arterial smooth muscle cell proliferation and migration in vitro and in vivo using local drug delivery. , 1997, Circulation.

[23]  H. Burt,et al.  Calcium pyrophosphate dihydrate crystals activate MAP kinase in human neutrophils: inhibition of MAP kinase, oxidase activation and degranulation responses of neutrophils by taxol , 1997, Immunology.

[24]  G. Viale,et al.  The microtubule-affecting drug paclitaxel has antiangiogenic activity. , 1996, Clinical cancer research : an official journal of the American Association for Cancer Research.

[25]  E. Lakatta,et al.  Taxol inhibits neointimal smooth muscle cell accumulation after angioplasty in the rat. , 1995, The Journal of clinical investigation.

[26]  W Rutsch,et al.  A comparison of balloon-expandable-stent implantation with balloon angioplasty in patients with coronary artery disease. Benestent Study Group. , 1994, The New England journal of medicine.

[27]  P. Teirstein,et al.  A randomized comparison of coronary-stent placement and balloon angioplasty in the treatment of coronary artery disease. Stent Restenosis Study Investigators. , 1994, The New England journal of medicine.

[28]  J. Reiber,et al.  A new approach for the quantification of complex lesion morphology: the gradient field transform; basic principles and validation results. , 1994, Journal of the American College of Cardiology.

[29]  J. Gallin,et al.  Effects of taxol on human neutrophils. , 1982, Journal of immunology.