Polymer-based paclitaxel-eluting stents reduce in-stent neointimal tissue proliferation A serial volumetric intravascular ultrasound analysis from the TAXUS-IV trial

ObjectivesThe aim of this study was to use serial volumetric intravascular ultrasound (IVUS) to evaluate the effects of polymer-based, paclitaxel-eluting stents on in-stent neointima formation and late incomplete stent apposition.BackgroundThe TAXUS-IV trial demonstrated that the slow-release, polymer-based, paclitaxel-eluting stent reduces angiographic restenosis and the need for repeat revascularization procedures. Serial IVUS studies reveal details of the pattern of vascular responses provoked by stent implantation that provide insight into device safety and efficacy.MethodsIn the TAXUS-IV trial, patients were randomized to the slow-release, polymer-based, paclitaxel-eluting TAXUS stent or a bare-metal EXPRESS stent (Boston Scientific Corp., Natick, Massachusetts). As part of a formal substudy, complete volumetric IVUS data were available in 170 patients, including 88 TAXUS patients and 82 controls, at implantation and at nine-month follow-up.ResultsNo baseline differences were present in the clinical characteristics or IVUS parameters between the control and TAXUS groups. At nine-month follow-up, IVUS lumen volumes were larger in the TAXUS group (123 ± 43 mm3vs. 104 ± 44 mm3, p = 0.005), due to a reduction in neointimal volume (18 ± 18 mm3vs. 41 ± 23 mm3, p < 0.001). Millimeter-by-millimeter analysis within the stent demonstrated uniform suppression of neointimal growth along the entire stent length. Late lumen loss was similar at the proximal edge of the stent between the two groups, and reduced with the TAXUS stent at the distal edge (p = 0.004). Incomplete stent apposition at nine months was observed in only 3.0% of control and 4.0% of TAXUS stents (p = 0.12).ConclusionsPolymer-based, paclitaxel-eluting TAXUS stents are effective in inhibiting neointimal tissue proliferation, and do not result in late incomplete stent apposition

Is glycoprotein IIb/IIIa antagonism as effective in women as in men following percutaneous coronary intervention? Lessons from the ESPRIT study

AbstractObjectivesThe study was done to determine whether eptifibatide, a platelet glycoprotein (GP) IIb/IIIa antagonist, prevents ischemic complications following percutaneous coronary interventions (PCIs) in women as well as in men.BackgroundEptifibatide reduces ischemic complications after nonurgent coronary stent interventions.MethodsWe compared outcomes in women (n = 562) and men (n = 1,502) enrolled in the Enhanced Suppression of the Platelet GP IIb/IIIa Receptor with Integrilin Therapy (ESPRIT) trial of double-bolus eptifibatide during PCI.ResultsWomen in the ESPRIT trial were older, and more frequently had hypertension, diabetes mellitus, or acute coronary syndromes, but were less likely to have prior PCI or coronary artery bypass graft surgery. The primary end point, a composite at 48 h of death, myocardial infarction (MI), urgent target vessel revascularization (TVR), and unplanned GP IIb/IIIa use, occurred in 10.5% of women and 7.9% of men (p = 0.082). The composite of death, MI, or TVR after one year occurred in 24.5% of women compared with 18% of men (p = 0.0008). At 48 h, eptifibatide reduced the composite of death, MI, and TVR from 14.5% to 6.0% in women versus 9.0% to 6.8% in men. At one year, these differences persisted: 28.9% versus 20.0% for women and 19.5% versus 16.6% for men. No statistical interaction existed between treatment and gender at either 48 h (p = 0.063) or one year (p = 0.2). Bleeding occurred more commonly in women (5.5% vs. 2.6%, p = 0.002), and was more common in eptifibatide-treated women. After adjustment for age, weight, and hypertension, no interaction between treatment and gender was present.ConclusionsEptifibatide is effective to prevent ischemic complications of PCI in women and may eliminate gender-related differences in PCI outcomes

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 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

One-year clinical results with the slow-release, polymer-based, paclitaxel-eluting TAXUS stent: the TAXUS-IV trial.

BACKGROUND: The safety and efficacy of the slow-release, polymer-based, paclitaxel-eluting stent after implantation in a broad cross section of de novo coronary lesions at 1 year are unknown. METHODS AND RESULTS: In the TAXUS-IV trial, 1314 patients with single de novo coronary lesions 10 to 28 mm in length, with reference-vessel diameter 2.5 to 3.75 mm, coverable by a single study stent, were prospectively randomized to the slow-release, polymer-based, paclitaxel-eluting TAXUS stent or an identical-appearing bare-metal EXPRESS stent. By actuarial analysis, the TAXUS stent compared with the bare-metal stent reduced the 12-month rates of target-lesion revascularization by 73% (4.4% versus 15.1%, P CONCLUSIONS: The relative efficacy reported at 9 months for the polymer-based, paclitaxel-eluting TAXUS stent compared with the EXPRESS stent is preserved and continues to increase at 1 year, with no safety concerns apparent

Long-Term Safety and Efficacy With Paclitaxel-Eluting Stents 5-Year Final Results of the TAXUS IV Clinical Trial (TAXUS IV-SR: Treatment of De Novo Coronary Disease Using a Single Paclitaxel-Eluting Stent)

ObjectivesThe pivotal TAXUS IV (TAXUS IV-SR: Treatment of De Novo Coronary Disease Using a Single Paclitaxel-Eluting Stent) trial evaluated the long-term safety and effectiveness of the paclitaxel-eluting stent (PES) compared with an otherwise identical bare-metal stent (BMS) in a relatively uncomplicated population of patients with a single de novo lesion in a native coronary vessel, treated between March and July 2002.BackgroundLong-term follow-up is required to determine whether the early safety and efficacy of drug-eluting stents are maintained.MethodsThe primary end point of this prospective, randomized, double-blind trial was 9-month ischemia-driven target vessel revascularization (TVR) for PES versus the BMS control. Follow-up was complete in 1,230 (95.1%) of 1,294 randomized evaluable patients at 5 years.ResultsCompared with BMS, PES significantly reduced TVR at 9 months (12.1% vs. 4.7%; p < 0.0001); this benefit was maintained through 5 years (27.4% vs. 16.9%; p < 0.0001), given comparable TVR rates for BMS and PES between years 1 and 5 (4.1%/year vs. 3.3%/year; respectively, p = 0.16). Similar patterns were observed for composite major adverse cardiac events (MACE) (32.8% BMS vs. 24.0% PES, p = 0.0001 at 5 years). Stent thrombosis was comparable for PES and BMS at 9 months (0.8% BMS vs. 0.8% PES; p = 0.98) and at 5 years (2.1% BMS vs. 2.2% PES, p = 0.87). The overall revascularization benefits of PES were consistent across multiple subgroups, including sex, diabetes, left anterior descending artery lesion location, reference vessel diameter, lesion length, and multiple stents.ConclusionsThese 5-year results demonstrate the long-term safety and sustained efficacy of PES compared with BMS in patients with noncomplex lesions. (TAXUS IV-SR: Treatment of De Novo Coronary Disease Using a Single Paclitaxel-Eluting Stent; NCT00292474

Relationship between angiographic late loss and target lesion revascularization after coronary stent implantation: analysis from the TAXUS-IV trial.

OBJECTIVES: We sought to evaluate the relationship between angiographic late loss and clinical outcomes in the drug-eluting stent era. BACKGROUND: The interrelationship between angiographic late loss, binary restenosis, and clinical recurrence (target lesion revascularization [TLR]) after coronary stent implantation has been incompletely evaluated. METHODS: Using the angiographic substudy of the TAXUS-IV trial, in which 1,314 patients with de novo coronary lesions were randomized to either the paclitaxel-eluting TAXUS stent or to its bare-metal equivalent, we defined the relationship between in-stent and analysis segment late loss, the shape of the late loss histogram (variance and skewedness), and nine-month TLR. RESULTS: Late loss by several measures was closely related to TLR (area under the receiver-operator curve \u3e0.90). For individual vessels of the size in this study (2.8 +/- 0.5 mm), the likelihood of TLR did not exceed 5% until analysis segment late loss was \u3e0.5 mm, and did not exceed 10% until late loss was \u3e0.65 mm. At greater late losses, the late loss TLR relationship was steep and nearly linear. For the overall patient cohort, the rate of TLR was related, however, not only to median late loss, but also to measures of its statistical distribution (TLR increased with lack of homogeneous biologic response [greater variance and greater right skewedness]). Similar relationships held for late loss measured within the confines of the stent itself. CONCLUSIONS: Coronary stents result in large lumens with room to accommodate up to approximately 0.5 to 0.65 mm of tissue (angiographic analysis segment late loss) before the likelihood of clinical restenosis (TLR) exceeds 5% to 10%. These data have important implications toward understanding the absolute and relative efficacy of drug-eluting stents