A provisional strategy for treating true bifurcation lesions employing a scoring balloon for the side branch: final results of the AGILITY trial.

BACKGROUND: The provisional approach for bifurcation stenting with side-branch balloon angioplasty is associated with dissections and suboptimal results requiring kissing balloon techniques or bailout stenting. We hypothesized that using a scoring balloon for the side branch and a drug-eluting stent for the main vessel might improve outcomes of true bifurcation lesions. METHODS AND RESULTS: A total of 93 patients with complex bifurcations were enrolled in a multicenter, single-arm, prospective clinical trial. A drug-eluting stent was deployed in the main vessel following dilatation of the side-branch stenosis with a scoring balloon. The overall angiographic success rate was 93.5%, and procedural success rate was 91.4%. The final diameter stenosis was 13.9% ± 7.2% for the main vessel and 33.3% ± 22.9% for the side branch. Crossover to stent deployment in the side branch was required in 10.8%. The postscoring balloon dissection rate was 8.2% and 6% (all ≤ class C) for the main vessel and side branch respectively, which was reduced to 1.1 and 2.1% poststenting. At 9-month follow-up, the composite MACE rate [cardiac death, myocardial infarction, or target lesion revascularization (TLR)] was 5.4%, including a TLR rate of 3.3% (1.1% from hospital discharge to 9 months). CONCLUSION: The 9-month results of the AGILITY trial support a simple provisional strategy for treating complex true bifurcation lesions with deployment of a drug-eluting stent in the main vessel after dilatation of the side-branch vessel with a scoring balloon. This strategy was associated with excellent and safe procedural results, a low rate of crossover to side-branch stenting, and favorable outcomes.

A randomized, controlled, multi-center trial comparing the safety and efficacy of zotarolimus-eluting and paclitaxel-eluting stents in de novo lesions in coronary arteries: final results of the ZoMaxx II trial.

BACKGROUND/OBJECTIVES: The purpose of this prospective, randomized, single-blind controlled clinical trial was to compare the effectiveness of a zotarolimus-eluting stent (ZoMaxx™) with a paclitaxel-eluting coronary stent (Taxus™ Express(2)™) in patients with angina pectoris and a single native coronary artery lesion between 10-28 mm in length and 2.5-3.75mm in diameter. METHODS: Patients were enrolled at 75 international institutions between June 2005 and November 2006. RESULTS: 1099 (1672 originally planned) patients received 557 ZoMaxx and 542 Taxus stents: cohorts were well-matched for diabetes (27% vs. 27%), reference vessel diameter (2.73 ± 0.46mm vs. 2.74 ± 0.45mm) and lesion length (14.8 ± 6.7mm vs. 14.3 ± 6.4mm). Nine month clinical and angiographic follow-up was available in 1052/1099 (96%) and 649/836 (78%) patients, respectively. The safety profiles for the two stents (myocardial infarction (MI), cardiac death and/or target vessel revascularization (TVR)) were similar (ZoMaxx 8.7% vs. Taxus 6.9%, p=NS). The primary endpoint of 9-month TVR occurred more frequently after treatment with ZoMaxx (6.8%) as compared with Taxus (4.2%), therefore the primary clinical endpoint was not met. However, the 9-month in-segment late lumen loss for ZoMaxx (0.29 ± 0.47mm) and Taxus (0.22 ± 0.41mm, p=NS) were similar, thus satisfying the primary angiographic endpoint. Secondary endpoints of the rates of in-segment and in-stent binary restenosis were also similar (5.9% vs. 5.8%, 7.8% vs. 7.9%, respectively). CONCLUSIONS: At 9months, the ZoMaxx stent failed to achieve the primary endpoint of non-inferiority in TVR to the Taxus stent, but safety endpoints were equal between the two stent systems.

Long-term benefit of the TAXUS Liberté stent in small vessels and long lesions. TAXUS ATLAS program.

BACKGROUND: The long-term impact of treating de novo coronary lesions in native vessels and challenging small vessel and long lesion subsets with TAXUS Liberté stents is unknown. This report examines the 3-year efficacy and safety from the TAXUS ATLAS program. METHODS AND RESULTS: TAXUS ATLAS WH, Small Vessel, and Long Lesion are non-randomized studies comparing TAXUS Liberté (n = 871), TAXUS Liberté 2.25 mm (n = 261), and TAXUS Liberté 38 mm (n = 150) stents, respectively, to case-matched TAXUS Express historical controls. TAXUS Liberté demonstrated comparable 3-year rates of major adverse cardiac events (19.0% vs. 20.2%, P = 0.51) in de novo lesions, reduced target lesion revascularization (TLR, 10.0% vs. 22.1%, P = 0.008) in small vessels, and reduced myocardial infarction (MI, 2.9% vs. 10.4%; P = 0.01) and stent thrombosis (ST, 0.0% vs. 3.9%, P = 0.03) in long lesions vs. TAXUS Express. After propensity score adjustment, no statistically significant effect of TAXUS Liberté on TLR (9.7% vs. 16.9%, P = 0.12) in small vessels or MI (2.9% vs. 7.9%, P = 0.05) in long lesions was noted, although reduced ST (0.0% vs. 2.7%, P = 0.02) remained in long lesions. Multivariate analyses demonstrated that TAXUS Liberté treatment significantly reduced TLR by 66% in small vessels, and MI by 75% in long lesions, vs. TAXUS Express. CONCLUSIONS: TAXUS Liberté suggests durable 3-year effectiveness in reducing restenosis and improved clinical outcomes in small vessels and long lesions compared with TAXUS Express.

Comparison of vascular response to zotarolimus-eluting stent vs paclitaxel-eluting stent implantation: pooled IVUS results from the ZoMaxx I and II trials.

BACKGROUND: The ZoMaxx I and II trials were randomized controlled studies of the zotarolimus-eluting, phosphorylcholine-coated, TriMaxx stent for the treatment of de novo coronary lesions. The aim of this study was to compare the vessel response between zotarolimus- (ZES) and paclitaxel-eluting stents (PES) using intravascular ultrasound (IVUS). METHODS AND RESULTS: Data were obtained from the ZoMaxx I and II trials, in which a standard IVUS parameter was available in 263 cases (baseline and 9-months follow up). Neointima-free frame ratio was calculated as the number of frames without IVUS-detectable neointima divided by the total number of frames within the stent. While an increase in vessel and plaque was observed in PES from baseline to follow up, there was no significant change in ZES. At follow up, % neointimal obstruction was significantly higher (15.4 ± 8.8% vs 11.3 ± 9.7%), and minimum lumen area at follow up was significantly smaller in ZES compared to PES. However, the incidence of IVUS-defined restenosis (maximum cross-sectional narrowing >60%) was similar in the 2 groups (3.2% vs 6.7%). Neointima-free frame ratio was significantly lower in ZES. There were 5 cases of late incomplete stent apposition in PES and none in ZES. CONCLUSIONS: These IVUS results demonstrate a similar incidence of severe narrowing between these 2 DES. There was a moderate increase in neointimal hyperplasia that was associated with a greater extent of neointimal coverage in ZES compared with PES.

TAXUS Liberté attenuates the risk of restenosis in patients with medically treated diabetes mellitus: results from the TAXUS ATLAS program.

OBJECTIVES: The aim of this study was to assess the relative efficacy and safety of the second-generation TAXUS Liberté paclitaxel-eluting stent (PES) in patients with and without diabetes mellitus. BACKGROUND: Diabetic patients suffer from accelerated atherosclerosis and increased risk of restenosis after coronary interventions; however, prior data suggest that PES might blunt this effect, providing equal benefit in diabetic and nondiabetic patients. METHODS: A pooled analysis of all 4 TAXUS ATLAS studies was conducted that included 413 diabetic and 1,116 nondiabetic subjects treated with the TAXUS Liberté stent for de novo coronary lesions. Angiographic and intravascular ultrasound outcomes at 9 months and clinical outcomes at 9 and 12 months were compared in patients with and without diabetes. Propensity score and multivariate adjustments were performed to correct for baseline differences. RESULTS: In-stent angiographic restenosis (13.0% vs. 9.6%, p = 0.12), late luminal loss (0.40 mm vs. 0.38 mm, p = 0.58), and intimal hyperplasia (14.8% vs. 13.4%, p = 0.29) were similar for diabetic and nondiabetic subjects. After propensity adjustment, 12-month target lesion revascularization rates were similar for diabetic and nondiabetic subjects (6.4% vs. 4.7%, p = 0.18), with no differences in mortality, myocardial infarction, or stent thrombosis. However, the rate of target vessel revascularization (TVR) was higher for diabetic subjects due to increased TVR outside the target lesion (TVR Remote). CONCLUSIONS: Similar clinical, angiographic, and intravascular ultrasound outcomes were observed for both diabetic and nondiabetic subjects treated with TAXUS Liberté, suggesting that this PES attenuates the effect of diabetes on restenosis after percutaneous coronary intervention, yielding comparable efficacy and safety in diabetic and nondiabetic patients. (TAXUS ATLAS; NCT00371709, NCT00371423, NCT00371748, and NCT00371475).

Two-year clinical outcomes after paclitaxel-eluting stent or brachytherapy treatment for bare metal stent restenosis: the TAXUS V ISR trial.

AIMS: This study sought to investigate the 2-year outcomes of patients treated with the paclitaxel-eluting TAXUS((R)) stent (PES) or vascular brachytherapy (VBT), the previous 'gold standard therapy', for bare metal stent in-stent restenosis (ISR). METHODS AND RESULTS: In the TAXUS V-ISR trial, 396 patients with bare metal stent ISR referred for percutaneous coronary intervention were prospectively randomized to either PES or beta source VBT. The present analysis reports 24-month clinical outcomes from that study. Between 9 and 24 months, ischaemia-driven target lesion revascularization tended to be required less frequently with assignment to PES compared to VBT (5.3 vs. 10.3%, P = .07). As a result, ischaemia-driven target lesion revascularization at 24 months was significantly reduced with PES compared with VBT (10.1 vs. 21.6%, P = 0.003), as was ischaemia-driven target vessel revascularization (18.1 vs. 27.5%, P = .03). There were no significant differences between the two groups with regard to death, myocardial infarction, or target vessel thrombosis either between 12 and 24 months, or cumulative to 24 months. CONCLUSION: Freedom from clinical restenosis at 2 years is significantly enhanced after PES placement compared with VBT for bare metal stent ISR, with similar rates of death, myocardial infarction, and target vessel thrombosis.

A novel bioresorbable polymer paclitaxel-eluting stent for the treatment of single and multivessel coronary disease: primary results of the COSTAR (Cobalt Chromium Stent With Antiproliferative for Restenosis) II study.

OBJECTIVES: The aim was to compare safety and effectiveness of the CoStar drug-eluting stent (DES) (Conor MedSystems, Menlo Park, California) with those of the Taxus DES (Boston Scientific, Maple Grove, Minnesota) in de novo single- and multivessel percutaneous coronary intervention (PCI). BACKGROUND: Paclitaxel elution from a stent coated with biostable polymer (Taxus) reduces restenosis after PCI. The CoStar DES is a novel stent with laser-cut reservoirs containing bioresorbable polymer loaded to elute 10 microg paclitaxel/30 days. METHODS: Patients undergoing PCI for a single target lesion per vessel in up to 3 native epicardial vessels were randomly assigned 3:2 to CoStar or Taxus. Primary end point was 8-month major adverse cardiac events (MACE), defined as adjudicated death, myocardial infarction (MI), or clinically driven target vessel revascularization (TVR). Protocol-specified 9-month angiographic follow-up included 457 vessels in 286 patients. RESULTS: Of the 1,700 patients enrolled, 1,675 (98.5%) were evaluable (CoStar = 989; Taxus = 686), including 1,330 (79%) single-vessel and 345 (21%) multivessel PCI. The MACE rate at 8 months was 11.0% for CoStar versus 6.9% for Taxus (p < 0.005), including adjudicated death (0.5% vs. 0.7%, respectively), MI (3.4% vs. 2.4%, respectively), and TVR (8.1% vs. 4.3%, respectively). Per-vessel 9-month in-segment late loss was 0.49 mm with CoStar and 0.18 mm with Taxus (p < 0.0001). Findings were consistent across pre-specified subgroups. CONCLUSIONS: The CoStar DES is not noninferior to the Taxus DES based on per-patient clinical and per-vessel angiographic analyses. The relative benefit of Taxus is primarily attributable to reduction in TVR. Follow-up to 9 months showed no apparent difference in death, MI, or stent thrombosis rates.

Reduced risk of restenosis in small vessels and reduced risk of myocardial infarction in long lesions with the new thin-strut TAXUS Liberté stent: 1-year results from the TAXUS ATLAS program.

OBJECTIVES: The TAXUS ATLAS Small Vessel (SV) and Long Lesion (LL) multicenter studies compared the performance of the thin-strut (0.0038 inch) TAXUS Liberté 2.25-mm stent (Boston Scientific; Natick, Massachusetts) and the TAXUS Liberté 38-mm long stent (Boston Scientific; Natick, Massachusetts) with the earlier paclitaxel-eluting TAXUS Express (Boston Scientific) stent that has identical polymer, drug dosage, and release kinetics but different stent geometry and thicker struts (0.0052 inch). BACKGROUND: The TAXUS Liberté stent was designed with thinner and more even strut spacing to provide more uniform drug distribution, as well as increased flexibility and conformability. Clinical benefits of the new stent design have not been evaluated. METHODS: The TAXUS ATLAS SV and LL studies are nonrandomized studies comparing outcomes of the TAXUS Liberté 2.25 mm (N = 261) and TAXUS Liberté 38 mm (N = 150) stents to TAXUS Express historical control groups derived from the TAXUS IV and V trials. Inclusion/exclusion criteria for TAXUS Express and Liberté groups were similar in both studies. RESULTS: Each study met its primary end point of noninferiority of 9-month in-segment diameter stenosis. Furthermore, TAXUS Liberté 2.25 mm, when compared with TAXUS Express, significantly reduced the rate of both 9-month angiographic restenosis (18.5% vs. 32.7%, p = 0.0219) and 12-month target lesion revascularization (6.1% vs. 16.9%, p = 0.0039). In addition, TAXUS Liberté 38 mm significantly reduced the risk of 12-month myocardial infarction compared with TAXUS Express (1.4% vs. 6.5%, p = 0.0246). CONCLUSIONS: The thinner-strut TAXUS Liberté stent improved outcomes compared with the earlier TAXUS Express stent in both SVs and LLs (A Study of the TAXUS Liberté Stent for the Treatment of de Novo Coronary Artery Lesions in Small Vessels; NCT00371748; A Study of the TAXUS Liberté Stent for the Treatment of Long De Novo Coronary Artery Lesions; NCT00371475).

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).

Comparison of the efficacy of direct coronary stenting with sirolimus-eluting stents versus stenting with predilation by intravascular ultrasound imaging (from the DIRECT trial).

A direct coronary stenting technique using drug-eluting stents may decrease drug-eluting stent efficacy due to possible damage to the surface coating of the stent. The DIRECT is a multicenter, prospective, nonrandomized trial designed to evaluate the direct stenting strategy for the sirolimus-eluting Bx-Velocity stent compared with the historical control (SIRIUS trial, stenting with predilation). Volumetric and cross-sectional intravascular ultrasound analyses at 8-month follow-up were performed in 115 patients (DIRECT n= 64, control n = 51). Patient and lesion characteristics were comparable between groups. The DIRECT group achieved an equivalent uniform expansion index, defined as minimum stent area/maximum stent area x 100, compared with the control group (65.9 +/- 11.7 vs 63.1 +/- 12.7, p = NS). At 8-month follow-up, vessel, stent, lumen, and neointimal volume index (volume in cubic millimeters/length in millimeters) and percent neointimal volume were similar between the DIRECT and control groups (vessel volume index 13.9 +/- 4.40 vs 15.0 +/- 3.83; stent volume index 6.83 +/- 2.02 vs 6.94 +/- 2.04; lumen volume index 6.71 +/- 2.04 vs 6.81 +/- 2.07; neointimal volume index 0.14 +/- 0.24 vs 0.16 +/- 0.23; percent neointimal volume 3.73 +/- 6.97 vs 3.14 +/- 5.32, p = NS for all). In addition, in-stent neointimal hyperplasia distribution was significantly smaller near the distal stent edge (0.22 vs 0.098 mm(3)/mm, p = 0.01 for an average neointimal volume index within 3 mm from the distal stent edge). In conclusion, direct coronary stenting with the sirolimus-eluting Bx-Velocity stent is equally effective in terms of uniform stent expansion and long-term quantitative intravascular ultrasound results compared with conventional stenting using predilation. This strategy appears to be associated with less neointimal hyperplasia near the distal stent edge.

Paclitaxel-eluting stents vs vascular brachytherapy for in-stent restenosis within bare-metal stents: the TAXUS V ISR randomized trial.

CONTEXT: Restenosis within bare-metal stents is often treated with repeat percutaneous coronary intervention, although subsequent recurrence rates are high, with vascular brachytherapy (VBT) affording the best results. The effectiveness of drug-eluting stents in this setting has not been established. OBJECTIVE: To investigate the safety and efficacy of the polymer-based, slow-release paclitaxel-eluting stent in patients with restenotic lesions after prior stent implantation in native coronary arteries. DESIGN, SETTING, AND PATIENTS: Prospective, multicenter, randomized trial conducted between June 6, 2003, and July 16, 2004, at 37 North American academic and community-based institutions in 396 patients with in-stent restenosis of a previously implanted bare-metal coronary stent (vessel diameter, 2.5-3.75 mm; lesion length, < or =46 mm). INTERVENTIONS: Patients were randomly assigned to undergo angioplasty followed by VBT with a beta source (n = 201) or paclitaxel-eluting stent implantation (n = 195). Clinical and angiographic follow-up at 9 months was scheduled in all patients. MAIN OUTCOME MEASURE: Ischemia-driven target vessel revascularization at 9 months. RESULTS: Diabetes mellitus was present in 139 patients (35.1%). Median reference vessel diameter was 2.65 mm and median lesion length was 15.3 mm. In the VBT group, new stents were implanted in 22 patients (10.9%) and in the paclitaxel-eluting stent group, multiple stents were required in 57 patients (29.2%), with median stent length of 24 mm. Follow-up at 9 months was complete in 194 patients in the VBT group and 191 patients in the paclitaxel-eluting stent group (96.5% and 97.9%, respectively). For VBT and paclitaxel-eluting stents, respectively, the number of events and 9-month rates for ischemic target lesion revascularization were 27 (13.9%) vs 12 (6.3%) (relative risk [RR], 0.45; 95% confidence interval [CI], 0.24-0.86; P = .01); for ischemic target vessel revascularization, 34 (17.5%) vs 20 (10.5%) (RR, 0.60; 95% CI, 0.36-1.00; P = .046); and for overall major adverse cardiac events, 39 (20.1%) vs 22 (11.5%) (RR, 0.57; 95% CI, 0.35-0.93; P = .02), with similar rates of cardiac death or myocardial infarction (10 [5.2%] vs 7 [3.7%]; RR, 0.71; 95% CI, 0.28-1.83; P = .48) and target vessel thrombosis (5 [2.6%] vs 3 [1.6%]; RR, 0.61; 95% CI, 0.15-2.50; P = .72). Angiographic restenosis at 9 months was 31.2% (53 of 170 patients) with VBT and 14.5% (25 of 172 patients) with paclitaxel-eluting stents (RR, 0.47; 95% CI, 0.30-0.71; P<.001). CONCLUSION: Treatment of bare-metal in-stent restenotic lesions with paclitaxel-eluting stents rather than angioplasty followed by VBT reduces clinical and angiographic restenosis at 9 months and improves event-free survival. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00287573.

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.