Comparison of vascular response to zotarolimus-eluting stent versus sirolimus-eluting stent: intravascular ultrasound results from ENDEAVOR III.

BACKGROUND: The purpose of this study was to investigate the vascular response of zotarolimus-eluting stent (ZES) and sirolimus-eluting stent (SES) using serial intravascular ultrasound (IVUS). METHODS: Data were obtained from the Endeavor Drug-Eluting Coronary Stent System Versus the Center Siromlimus-Eluting Coronary Stent System in De Novo Native Coronary Artery Lesions (ENDEAVOR) III trial, a randomized study comparing ZES and SES for the treatment of de novo native coronary artery lesions. Serial (baseline and 8-month follow-up) IVUS was available in 258 patients (190 ZES, 68 SES). RESULTS: At 8 months, ZES had greater percentage of neointimal volume index (ZES 1.1 +/- 0.8 mm3/mm vs SES 0.2 +/- 0.1 mm3/mm, P < .01), resulting in smaller lumen volume index (6.0 +/- 2.0 mm3/mm vs 7.0 +/- 2.1 mm3/mm, P < .05). Zotarolimus-eluting stents showed larger IVUS-detectable neointimal coverage over stent surface (50.2% vs 10.5%, P < .01) and greater mean neointimal thickness (0.19 +/- 0.07 mm vs 0.10 +/- 0.06 mm, P < .01). Zotarolimus-eluting stents had a significantly lower incidence of late-acquired incomplete stent apposition. CONCLUSIONS: Zotarolimus-eluting stent is associated with a significantly greater amount of neointimal hyperplasia compared with SES. This amount of hyperplasia in ZES is distributed throughout the stent at 8-month follow-up.

Detailed intravascular ultrasound analysis of Zotarolimus-eluting phosphorylcholine-coated cobalt-chromium alloy stent in de novo coronary lesions (results from the ENDEAVOR II trial).

Zotarolimus-eluting phosphorylcholine-coated cobalt-chromium alloy Driver stents (ZES) demonstrated significant reductions in target lesion revascularization rate with few apparent adverse events compared with bare metal stents (BMS; uncoated Driver stents) in a prospective, multicenter, double-blind, randomized controlled trial in de novo coronary lesions. The aim of this study was to examine detailed vascular responses to ZES compared with BMS using serial intravascular ultrasound analysis. A total of 343 patients (ZES n = 178, BMS n = 165) were enrolled in this formal, prespecified intravascular ultrasound substudy of the Randomized Controlled Trial to Evaluate the Safety and Efficacy of the Medtronic AVE Zotarolimus-Eluting Driver Coronary Stent in de Novo Native Coronary Artery Lesions (ENDEAVOR II), a prospective, multicenter, double-blind, randomized controlled trial to compare ZES and BMS in de novo native coronary artery lesions. Quantitative and qualitative intravascular ultrasound analyses were performed postprocedurally and at 8-month follow-up in stented and reference segments. ZES showed significantly less neointima, with a larger lumen than BMS at 8 months (percentage neointimal volume 17.6 +/- 10.1% vs 29.4 +/- 17.2%, p <0.0001; maximum percentage neointimal area 32.9 +/- 13.0% vs 47.6 +/- 18.6%, p <0.0001; minimum luminal area 4.9 +/- 1.6 vs 4.0 +/- 1.7 mm(2), p <0.0001) and no unfavorable edge effect. In the 18-mm single stents, ZES showed evenly inhibited neointima compared with BMS. Neither persistent stent-edge dissection nor late-acquired incomplete stent apposition was observed in either group. In conclusion, ZES showed evenly inhibited neointima with no apparent adverse vascular response in stented and reference segments at 8 months compared with BMS.

Intravascular ultrasonic analysis of atherosclerotic vessel remodeling and plaque distribution of stenotic left anterior descending coronary arterial bifurcation lesions upstream and downstream of the side branch.

Bifurcation lesions remain a challenging lesion subset, even in the era of drug-eluting stents. The aim of this study was to investigate the longitudinal remodeling pattern and cross-sectional plaque location of bifurcation lesions. Seventy-four preintervention intravascular ultrasound studies of left anterior descending bifurcation lesions were analyzed, in which the lesion was located proximal (type A, n=32) or distal (type B, n=42) to the side branch. Vessel area and plaque area at the lesion (VAlesion and PAlesion) and at the reference site (VAreference and PAreference) were measured. The remodeling ratio was defined as VAlesion/VAreference, and the vessel compensation ratio was defined as (VAlesion-VAreference)/(PAlesion-PAreference). The geometric center of the lumen at the lesion site was identified, and the lesion site was divided into circumferential equal arcs to compare the cross-sectional distribution of percentage plaque area (100x[PAlesion/VAlesion]) between the 2 groups. The remodeling ratio (1.03+/-0.15 vs 0.94+/-0.14, p=0.01) and the vessel compensation ratio (0.0+/-0.36 vs -0.37+/-0.61, p<0.01) were significantly greater in type A than in type B lesions. The circumferential distribution pattern of percentage plaque area was significantly different between the groups (analysis of variance p<0.005), with greater percentage plaque area for the vessel wall opposite from the side branch in type B lesions (46.3+/-18.0% vs 54.6+/-15.4%, type A vs type B lesions, p<0.05). In conclusion, these results suggest that a major side branch may affect longitudinal lesion remodeling as well as the circumferential location of atherosclerotic plaque.

Augmentation of tissue perfusion by a novel compression device increases neurologically intact survival in a porcine model of prolonged cardiac arrest.

OBJECTIVE: This study was performed to determine the potential efficacy of an automated device with a load-distributing band (AutoPulse, Revivant Corporation), in improving neurologically intact survival after cardiac arrest. DESIGN: Randomized, controlled trial. SETTING: University animal laboratory. SUBJECTS: Forty-four swine (18-23 kg). INTERVENTIONS: Eight minutes after induction of untreated ventricular fibrillation, pigs were randomized to AutoPulse-CPR (A-CPR, n = 22), conventional cardiopulmonary resuscitation (CPR) with 20% anterior-posterior chest displacement (C-CPR20, n = 10) or 30% chest displacement (C-CPR30, n = 12), followed by resuscitation protocol with ventilation, defibrillation and intravenous epinephrine (adrenaline). MEASUREMENTS AND MAIN RESULTS: Aortic and right atrium blood pressure was measured with micromanometers. Regional blood flows were measured with microspheres. Coronary perfusion pressure during A-CPR was significantly higher as compared to C-CPR without epinephrine (A-CPR versus C-CPR20 versus C-CPR30; 16 +/- 1 mmHg versus 7 +/- 2 mmHg versus 11 +/- 2 mmHg, p < 0.05). A-CPR improved both myocardial flow without epinephrine (A-CPR versus C-CPR20 versus C-CPR30; 23% versus 0% versus 4%; percent of baseline, p < 0.05) and cerebral blood flow (40% versus 4% versus 19%, percent of baseline, p < 0.05). Sixteen of 22 animals receiving A-CPR regained spontaneous circulation and survived; 14/22 had normal cerebral performance (CPC 1). Four of 12 animals receiving C-CPR30 regained spontaneous circulation and survived, but only one animal had normal neurological function (14/22 versus 1/12, p < 0.0001). No animal receiving C-CPR20 achieved spontaneous circulation. At necropsy, 67% of C-CPR30 had rib fracture and 33% showed lung injury, while A-CPR and C-CPR20 resulted in no detectable injuries. CONCLUSIONS: Improved hemodynamics with AutoPulse performed CPR results in improved neurologically intact survival without subsequent thoracic or pulmonary injuries in this porcine model of prolonged cardiac arrest.

Sex differences in neointimal hyperplasia following endeavor zotarolimus-eluting stent implantation.

Inconsistent results in outcomes have been observed between the genders after drug-eluting stent implantation. The aim of this study was to investigate gender differences in neointimal proliferation for the Endeavor zotarolimus-eluting stent (ZES) and the Driver bare-metal stent (BMS). A total of 476 (n = 391 ZES, n = 85 BMS) patients whose volumetric intravascular ultrasound analyses were available at 8-month follow-up were studied. At 8 months, neointimal obstruction and maximum cross-sectional narrowing (CSN) were significantly lower in women than in men receiving ZES (neointimal obstruction 15.5 ± 9.5% vs 18.2 ± 10.9%, p = 0.025; maximum CSN 30.3 ± 13.2% vs 34.8 ± 15.0%, p = 0.007). Conversely, these parameters tended to be higher in women than in men receiving BMS (neointimal obstruction 36.3 ± 15.9% vs 27.5 ± 17.2%, p = 0.053; maximum CSN 54.3 ± 18.6% vs 45.6 ± 18.3%, p = 0.080). There was a significant interaction between stent type and gender regarding neointimal obstruction (p = 0.001) and maximum CSN (p = 0.003). Multivariate linear regression analysis revealed that female gender was independently associated with lower neointimal obstruction (p = 0.027) and maximum CSN (p = 0.004) for ZES but not for BMS. Compared to BMS, ZES were independently associated with a reduced risk for binary restenosis in both genders (odds ratio for women 0.003, p = 0.001; odds ratio for men 0.191, p <0.001), but the magnitude of this risk reduction with ZES was significantly greater in women than men (p = 0.015). In conclusion, female gender is independently associated with decreased neointimal hyperplasia in patients treated with ZES. The magnitude of risk reduction for binary restenosis with ZES is significantly greater in women than in men.

Impact of polymer formulations on neointimal proliferation after zotarolimus-eluting stent with different polymers: insights from the RESOLUTE trial.

BACKGROUND: Polymer formulation may affect the efficacy of drug-eluting stents. Resolute, Endeavor, and ZoMaxx are zotarolimus-eluting stents with different stent platforms and different polymer coatings and have been tested in clinical trials. The aim of this analysis was to compare the efficacy of zotarolimus-eluting stents with different polymers. METHODS AND RESULTS: Data were obtained from the first-in man trial or first randomized trials of each stent, The Clinical RESpOnse EvaLUation of the MedTronic Endeavor CR ABT-578 Eluting Coronary Stent System in De Novo Native Coronary Artery Lesions (RESOLUTE), Randomized Controlled Trial to Evaluate the Safety and Efficacy of the Medtronic AVE ABT-578 Eluting Driver Coronary Stent in De Novo Native Coronary Artery Lesions (ENDEAVOR II), and ZoMaxx I trials. Follow-up intravascular ultrasound analyses (8 to 9 months of follow-up) were possible in 353 patients (Resolute: 88, Endeavor: 98, ZoMaxx: 82, Driver: 85). Volume index (volume/stent length) was obtained for vessel, stent, lumen, peristent plaque, and neointima. Cross-sectional narrowing was defined as neointimal area divided by stent area (%). Neointima-free frame ratio was calculated as the number of frames without intravascular ultrasound-detectable neointima divided by the total number of frames within the stent. At baseline, vessel, lumen, and peristent plaque volume index were not significantly different among the 4 stent groups. At follow-up, percent neointimal obstruction was significantly lower in Resolute compared with Endeavor, ZoMaxx, and Driver (Resolute: 3.7±4.0, Endeavor: 17.5±10.1, ZoMaxx: 14.6±8.1, Driver: 29.4±17.2%; P<0.001). Greater maximum cross-sectional narrowing and higher neointima-free frame ratio, suggesting less neointimal coverage, were observed in Resolute compared with other stent groups. Multiple regression analysis confirmed that the biodurable polymer used in Resolute independently correlated with neointimal suppression among 3 zotarolimus-eluting stents. CONCLUSIONS: The different polymer formulations significantly affect the relative amount of neointima for zotarolimus-eluting stents. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00248079.

Comparison of vessel response following sirolimus-eluting stent implantation as assessed by serial 3-D intravascular ultrasound study.

Recent sirolimus-eluting stent (SES) studies have suggested higher rates of restenosis in non-left anterior descending (LAD) artery lesions. The aim of this study was to evaluate differential vessel response (LAD versus non-LAD) to SES implantation using serial intravascular ultrasound (IVUS). A total of 94 patients who underwent SES implantation and serial (post-PCI and 8 months) 3-dimensional IVUS were enrolled from our database. Volumetric analysis was performed throughout the stent as well as the adjacent reference segment (up to 5 mm). Volume index (volume/length) was calculated for vessel (VVI), lumen (LVI), and plaque (PVI). Cross-sectional narrowing (CSN) was defined as neointimal area divided by stent area (%). With respect to the in-stent segment, VVI, PVI, and LVI at post-PCI were not significantly different between the LAD (n = 41) and non-LAD (n = 53) lesions. At follow up, however, maximum CSN was significantly greater in the non-LAD lesions (18.3 +/- 15.2% versus 12.2 +/- 10.0%; p = 0.029). At the proximal reference segment, the non-LAD lesions showed a significantly greater LVI decrease than the LAD lesions (p <0.05), primarily due to mild vessel shrinkage observed in the non-LAD lesions. There were no significant differences at the distal reference segment between the LAD and non-LAD lesions. This detailed IVUS analysis suggests that there are minimal differences in the vessel responses following SES implantation. These findings may have potential implications for mechanical and pharmacokinetic properties of next-generation drug-eluting stent technology.

Mechanism of luminal gain with plaque excision in atherosclerotic coronary and peripheral arteries: assessment by histology and intravascular ultrasound.

OBJECTIVES: Using intravascular ultrasound (IVUS) and histology, the purpose of this study was to evaluate the occurrence of arterial wall overstretch and Dotter effect following revascularization with a plaque excision (PE) catheter compared with balloon angioplasty. BACKGROUND: Previous studies have demonstrated the safety and feasibility of plaque excision for the treatment of de novo coronary and peripheral atherosclerotic disease. However, whether mechanical vessel dilatation related to catheter insertion contributes to gains in the final luminal diameter is uncertain. METHODS: Treatment with PE was assessed in both a porcine model (6 lesions treated with balloon angioplasty or PE) using histology and in humans with IVUS. In the latter part of the study, IVUS study was performed before and immediately following PE in 21 patients with either coronary artery disease (N = 13) or femoral artery disease (N = 8). Ultrasound measures in the femoral artery group were then compared with a control group of atherosclerotic lesions treated with conventional angioplasty that was matched according to lesion location and vessel diameter. RESULTS: Among individuals with coronary and peripheral arterial lesions treated with PE, the relative increases in luminal area secondary to reductions in plaque volume were 89% and 83%, respectively, with minimal increase in vessel diameter. In contrast, balloon angioplasty was associated with significantly greater vessel expansion and less plaque volume reduction. Vessel dissection also tended to occur less frequently and to a lesser extent with PE. CONCLUSIONS: Improvement in luminal dimensions using PE is principally due to a reduction in plaque volume rather than mechanical vessel expansion. The potential to increase luminal area while minimizing arterial dissection and barotrauma merits further clinical study with this method of revascularization.