Meta-analysis of angiographic versus intravascular ultrasound parameters of drug-eluting stent efficacy (from TAXUS IV, V, and VI).

Both quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS) are currently used to assess in-stent restenosis. This study aimed to use standardized imaging and clinical follow-up to compare QCA parameters with several IVUS parameters to evaluate their strengths and weaknesses for detecting in-stent restenosis in a drug-eluting stent population. A subset of patients from the TAXUS IV, V, and VI studies was evaluated. The subset, which included 216 TAXUS-treated patients and 191 bare-metal stent-treated patients, had complete IVUS and QCA performed at baseline and follow-up. As expected, all QCA and IVUS parameters were consistent with less intimal hyperplasia in TAXUS patients than controls. The overall incidence of QCA binary restenosis was 14.0%, which was 9.3% in TAXUS-treated patients and 19% in bare-metal stent-treated patients (p = 0.0008). Regression analysis showed that QCA late lumen loss and percentage of diameter stenosis correlated only moderately with the various IVUS measures of neointimal hyperplasia for the combined group of patients (TAXUS + bare-metal stent), as well as for the TAXUS-treated and bare-metal stent-treated patients separately. However, in general, correlations within the control (bare-metal stent) group tended to be stronger than within the TAXUS group. The strongest correlation was between QCA percentage of diameter stenosis and IVUS percentage of intimal hyperplasia in the overall group and the control group. The strongest IVUS predictor of QCA binary restenosis at 9 months was maximum percentage of intimal hyperplasia, with an overall C = 0.91 and p <0.001. In conclusion, the QCA and IVUS parameters used to evaluate drug-eluting stent efficacy showed a moderate correlation with IVUS percentage of intimal hyperplasia, reliably predicting QCA binary in-stent restenosis.

Peristent remodeling and neointimal suppression 2 years after polymer-based, paclitaxel-eluting stent implantation: insights from serial intravascular ultrasound analysis in the TAXUS II study.

BACKGROUND: The purpose of this study was to evaluate long-term vascular responses as long as 2 years after implantation of polymer-based, paclitaxel-eluting stents in contrast to uncoated stents. METHODS AND RESULTS: TAXUS II is a randomized, double-blind trial comparing slow-release (SR) and moderate-release (MR) TAXUS stents with bare-metal control stents (BMSs). One hundred sixty-one event-free patients (SR, 43; MR, 41; and BMS, 77) underwent serial intravascular ultrasound (IVUS) analysis after the procedure and at 6 months and 2 years. At 2 years, neointimal responses continued to be significantly suppressed in the SR and MR groups when compared with the BMS group (BMS, 1.49+/-1.12 mm2; SR, 0.94+/-0.76 mm2 [P=0.004]; and MR, 1.06+/-0.90 mm2 [P=0.02]). Between 6 months and 2 years, the BMS group showed compaction of the neointima (Delta, -0.22+/-1.05 mm2 [P=0.08]). In contrast, both the SR and MR groups exhibited an increase (Delta SR, 0.30+/-0.76 mm2 (P=0.01); MR, 0.41+/-0.94 mm2 [P=0.009]). Between 6 months and 2 years, the initial increase in plaque outside the stent regressed in the BMS and SR groups to levels comparable to those after the procedure, whereas expansive remodeling partially regressed in the MR group (Delta between after the procedure and 2 years BMS, -0.34+/-1.28 mm2 [P=0.05]; SR, -0.02+/-1.40 mm2 [P=0.93]; MR, 0.32+/-1.56 mm2 [P=0.27]). CONCLUSIONS: The 2-year follow-up demonstrates that neointimal suppression was dose independent and that this effect was still sustained at 2 years. However, the increase in area outside the stent seen at 6 months regressed to different extents in a dose-dependent manner at 2 years.

Clinical efficacy of polymer-based paclitaxel-eluting stents in the treatment of complex, long coronary artery lesions from a multicenter, randomized trial: support for the use of drug-eluting stents in contemporary clinical practice.

BACKGROUND: Intracoronary polymer-based stent delivery of paclitaxel has been shown to be effective in reducing restenosis in simple coronary lesions, but the evidence base for contemporary use in longer, more complex coronary stenoses is lacking. METHODS AND RESULTS: TAXUS VI is a prospective, multicenter, double-blind, randomized trial assessing clinical and angiographic outcomes of the TAXUS Moderate Release paclitaxel-eluting stent in the treatment of long, complex coronary artery lesions. Four hundred forty-eight patients at 44 sites were randomized (1:1) between a drug-eluting TAXUS Express2 and an uncoated Express2 control stent. Per protocol, the 9-month follow-up included an angiographic reevaluation in all patients. The primary end point was the rate of target-vessel revascularization 9 months after the study procedure; secondary end points included the rate of target-lesion revascularization and binary restenosis at follow-up. Mean lesion length in the study was 20.6 mm, with a mean stent-covered length of 33.4 mm. Of all lesions, 55.6% were classified as complex lesions (type C of the AHA/ACC classification). At 9 months, target-vessel revascularization was 9.1% in the TAXUS group and 19.4% in the control group (P=0.0027; relative reduction, 53%). Target-lesion revascularization was reduced from 18.9% to 6.8%, respectively (P=0.0001). The incidence of major adverse cardiac events was similar in the 2 groups, 16.4% and 22.5% in TAXUS and control, respectively (P=0.12), including comparable rates for acute myocardial infarction. Binary restenosis in the stented area was reduced from 32.9% in the control group to 9.1% in the TAXUS patients (P<0.0001). CONCLUSIONS: The finding that the TAXUS Moderate Release stent system is safe and effective in the treatment of long, complex coronary artery lesions provides the evidence base for the more widespread use of drug-eluting stents in contemporary clinical practice.

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

OBJECTIVES: The 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. BACKGROUND: The 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. METHODS: In 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. RESULTS: No 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 mm(3) vs. 104 +/- 44 mm(3), p = 0.005), due to a reduction in neointimal volume (18 +/- 18 mm(3) vs. 41 +/- 23 mm(3), 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). CONCLUSIONS: Polymer-based, paclitaxel-eluting TAXUS stents are effective in inhibiting neointimal tissue proliferation, and do not result in late incomplete stent apposition.

Comparison of a polymer-based paclitaxel-eluting stent with a bare metal stent in patients with complex coronary artery disease: a randomized controlled trial.

CONTEXT: Compared with bare metal stents, drug-eluting stents reduce restenosis in noncomplex lesions. The utility of drug-eluting stents has not been evaluated in more difficult stenoses. OBJECTIVE: To investigate the safety and efficacy of the polymer-based, slow-release paclitaxel-eluting stent in a patient population with more complex lesions than previously studied. DESIGN, SETTING, AND PATIENTS: Prospective, placebo-controlled, double-blind, multicenter randomized trial conducted from February 2003 to March 2004 at 66 academic and community-based institutions with 1156 patients who underwent stent implantation in a single coronary artery stenosis (vessel diameter, 2.25-4.0 mm; lesion length, 10-46 mm), including 664 patients (57.4%) with complex or previously unstudied lesions (requiring 2.25-mm, 4.0-mm, and/or multiple stents) and 9-month clinical and angiographic follow-up. INTERVENTIONS: Patients were randomly assigned to receive 1 or more bare metal stents (n = 579) or identical-appearing paclitaxel-eluting stents (n = 577). MAIN OUTCOME MEASURE: Ischemia-driven target vessel revascularization at 9 months. RESULTS: Baseline characteristics were well matched. Diabetes was present in 31% of patients. The mean (SD) reference vessel diameter was 2.69 (0.57) mm, the reference lesion length was 17.2 (9.2) mm, and 78% of lesions were type B2/C. A mean (SD) of 1.38 (0.58) stents (total mean [SD] length, 28.4 [13.1] mm) were implanted per lesion; 33% of lesions required multiple stents. Stents that were 2.25 mm and 4.0 mm in diameter were used in 18% and 17% of lesions, respectively. Compared with bare metal stents, paclitaxel-eluting stents reduced the 9-month rate of target lesion revascularization from 15.7% to 8.6% (P<.001) and target vessel revascularization from 17.3% to 12.1% (P = .02). Similar rates were observed for cardiac death or myocardial infarction (5.5% for bare metal stent group vs 5.7% for paclitaxel-eluting stent group) and stent thrombosis (0.7% in both groups). Angiographic restenosis was reduced from 33.9% to 18.9% in the entire study cohort (P<.001), including among patients receiving 2.25-mm stents (49.4% vs 31.2%; P = .01), 4.0-mm stents (14.4% vs 3.5%; P = .02), and multiple stents (57.8% vs 27.2%; P<.001). CONCLUSION: Compared with a bare metal stent, implantation of the paclitaxel-eluting stent in a patient population with complex lesions effectively reduces clinical and angiographic restenosis.

Effect of the polymer-based, paclitaxel-eluting TAXUS Express stent on vascular tissue responses: a volumetric intravascular ultrasound integrated analysis from the TAXUS IV, V, and VI trials.

AIMS: The TAXUS Express stent has been shown to reduce angiographic restenosis, repeat revascularizations, and neointimal hyperplasia when compared with bare metal stent (BMS) control (TAXUS IV, V, and VI) in individual TAXUS trials. Since intravascular ultrasound (IVUS) methodology and core laboratory were consistent among all three TAXUS trials, an integrated analysis of 956 patients across all IVUS cohorts can be performed providing superior power. METHODS AND RESULTS: In the TAXUS randomized trials, patients received an Express BMS or paclitaxel-eluting TAXUS Express stent. Volumetric analysis was performed on a selected subgroup at implantation and 9 months. Compared with BMS control, TAXUS increased 9-month lumen volumes (144 +/- 79 vs. 179 +/- 95 mm(3); P < 0.0001) due to reduced neointimal volume (66 +/- 49 vs. 27 +/- 30 mm(3); P < 0.0001). This corresponded to a 61% decrease in net lumen volume obstruction (31 +/- 15 vs. 12 +/- 12 mm(3); P < 0.0001). Lumen loss was similar between groups for the proximal 5 mm outside the stent but was reduced in TAXUS at the distal edge (P = 0.0056). Neointimal hyperplasia was significantly reduced in the double-strut region of overlapping TAXUS vs. BMS control and in high-risk patients with diabetes, long lesions, multiple stents, and multiple overlapping stents. Late-acquired incomplete stent apposition (ISA) was more common with moderate-release TAXUS stents. Importantly, there were no major adverse cardiac events or stent thromboses in any late-acquired ISA patient through 2 years. Univariate and multivariable analyses revealed that longer lesion length and previous myocardial infarction are risk factors for late-acquired ISA. CONCLUSION: Integrated analysis of the TAXUS trials shows that the paclitaxel-eluting TAXUS Express stent effectively inhibits in-stent neointimal proliferation, even in high-risk and overlapping stent patients.

Polymer-based, paclitaxel-eluting TAXUS Liberté stent in de novo lesions: the pivotal TAXUS ATLAS trial.

OBJECTIVES: The goal of this research was to assess non-inferiority of the next-generation TAXUS Liberté stent (Boston Scientific Corp., Natick, Massachusetts) versus the TAXUS Express stent (Boston Scientific Corp.). BACKGROUND: The introduction of drug-eluting stents (DES) has shifted clinical practice towards more complex lesion subsets, prompting the need for more deliverable DES. TAXUS Liberté was designed to combine the established polymer-based, paclitaxel-elution TAXUS technology with the more advanced Liberté stent platform. METHODS: The TAXUS ATLAS study is a global, prospective, single-arm trial evaluating outcomes in de novo coronary lesions visually estimated to be 10 to 28 mm in length in vessels 2.5 to 4.0 mm in diameter. The control group is an entry-criteria-matched population of TAXUS Express patients from the TAXUS IV and V trials. The primary end point is non-inferiority of TAXUS Liberté versus TAXUS Express for 9-month target vessel revascularization. RESULTS: Despite similar inclusion criteria, quantitative coronary angiography-determined baseline lesion characteristics were significantly more complex for TAXUS Liberté than TAXUS Express. The primary non-inferiority end point was met with the 1-sided 95% confidence bound of 2.98% less than the pre-specified non-inferiority margin of 3% (p = 0.0487). CONCLUSIONS: Despite the treatment of more complex lesions with TAXUS Liberté, the primary end point was met, demonstrating that TAXUS Liberté is non-inferior to TAXUS Express. The successful transfer of the proven TAXUS technology to the more advanced TAXUS Liberté platform was demonstrated. (TAXUS ATLAS: TAXUS Liberté-SR Stent for the Treatment of De Novo Coronary Artery Lesions; http://www.clinicaltrials.gov/ct/show/NCT00371709?order=1; NCT00371709).

TAXUS VI 2-year follow-up: randomized comparison of polymer-based paclitaxel-eluting with bare metal stents for treatment of long, complex lesions.

AIMS: Drug-eluting stents (DESs) have shown to be effective in reducing in-stent restenosis, although data relating to long-term experience in treating more complex lesion subsets are limited. In order to assess the long-term safety and clinical efficacy of the polymer-based moderate release (MR) paclitaxel-eluting TAXUS MR stent in treatment of complex lesion subsets, we evaluated the 2-year follow-up of TAXUS VI. METHOD AND RESULTS: TAXUS VI was a randomized multi-centre study enrolling 446 patients with complex lesions, including small vessels in 28% of patients and a mean lesion length of 20.6 mm. At 9-month follow-up, the use of the TAXUS MR stent was highly effective, resulting in a significant 53% reduction of the target vessel revascularization (TVR) rate (primary endpoint) from 19.4% in the control group to 9.1% in the TAXUS group (P = 0.0027). Clinical follow-up at 2 years post-stenting was available in 98.6% of the TAXUS group and 95.6% of the control group. The incidence of major adverse cardiac event at 1- and 2-year follow-up was 16.4% and 21.3% in the TAXUS group when compared with 22.5 and 25.1% in the control group, respectively. A significant difference in TVR was maintained at 2-year follow-up (TAXUS 13.9%; control 21.9%; P = 0.0335). The cumulative 1- and 2-year survival rates free from TVR were, respectively, 91.7 and 90.3% in the TAXUS group vs. 80.0 and 79.0% in the control group (log-rank P < 0.001). The number of patients required to be treated with a TAXUS stent to prevent one re-percutaneous coronary intervention at 2 years was 12.5. CONCLUSION: Treatment of complex coronary lesions with the polymer-based MR paclitaxel-eluting TAXUS MR stent is associated with a sustained clinical benefit and low rates of TVR up to 2 years after device implantation.

An overview of the TAXUS Express, paclitaxel-eluting stent clinical trial program.

Restenosis remains a problem following percutaneous coronary intervention in patients with coronary artery disease. Drug-eluting stents (DES), which combine mechanical and pharmacologic properties, have been shown to prevent or reduce neointimal growth after deployment. This review describes the TAXUS paclitaxel-eluting stent clinical trial expansion program (TAXUS Express, Boston Scientific, Natick, MA). This program comprises the largest data set of randomized controlled trials (RCTs) of DES to date, with over 6,200 patients enrolled since 2000. The program includes treatment of de novo lesions, as well as higher-risk lesion and patient populations. In this review, we discuss the results from the TAXUS family of randomized clinical trials, and compare the findings with data from TAXUS registries. The data from the randomized clinical trials suggest that the paclitaxel-eluting stent provides consistent and durable benefits across multiple lesion and patient types. Evidence from peri-and post-approval registries, where patient populations are more heterogeneous than those eligible and included in the RCTs, corroborate these findings, with overall low rates of cardiac events, including reinterventions.