ABSORB II randomized controlled trial: a clinical evaluation to compare the safety, efficacy, and performance of the Absorb everolimus-eluting bioresorbable vascular scaffold system against the XIENCE everolimus-eluting coronary stent system in the treatment of subjects with ischemic heart disease caused by de novo native coronary artery lesions: rationale and study design.

BACKGROUND: Currently, no data are available on the direct comparison between the Absorb everolimus-eluting bioresorbable vascular scaffold (Absorb BVS) and conventional metallic drug-eluting stents. METHODS: The ABSORB II study is a randomized, active-controlled, single-blinded, multicenter clinical trial aiming to compare the second-generation Absorb BVS with the XIENCE everolimus-eluting metallic stent. Approximately 501 subjects will be enrolled on a 2:1 randomization basis (Absorb BVS/XIENCE stent) in approximately 40 investigational sites across Europe and New Zealand. Treated lesions will be up to 2 de novo native coronary artery lesions, each located in different major epicardial vessels, all with an angiographic maximal luminal diameter between 2.25 and 3.8 mm as estimated by online quantitative coronary angiography (QCA) and a lesion length of ≤48 mm. Clinical follow-up is planned at 30 and 180 days and at 1, 2, and 3 years. All subjects will undergo coronary angiography, intravascular ultrasound (IVUS) and IVUS-virtual histology at baseline (pre-device and post-device implantation) and at 2-year angiographic follow-up. The primary end point is superiority of the Absorb BVS vs XIENCE stent in terms of vasomotor reactivity of the treated segment at 2 years, defined as the QCA quantified change in the mean lumen diameter prenitrate and postnitrate administration. The coprimary end point is the noninferiority (reflex to superiority) of the QCA-derived minimum lumen diameter at 2 years postnitrate minus minimum lumen diameter postprocedure postnitrate by QCA. In addition, all subjects allocated to the Absorb BVS group will undergo multislice computed tomography imaging at 3 years. CONCLUSIONS: The ABSORB II randomized controlled trial (ClinicalTrials.gov NCT01425281) is designed to compare the safety, efficacy, and performance of Absorb BVS against the XIENCE everolimus-eluting stent in the treatment of de novo native coronary artery lesions.

Evaluation of the second generation of a bioresorbable everolimus drug-eluting vascular scaffold for treatment of de novo coronary artery stenosis: six-month clinical and imaging outcomes.

BACKGROUND: The first generation of the bioresorbable everolimus drug-eluting vascular scaffold showed signs of shrinkage at 6 months, which largely contributed to late luminal loss. Nevertheless, late luminal loss was less than that observed with bare metal stents. To maintain the mechanical integrity of the device up to 6 months, the scaffold design and manufacturing process of its polymer were modified. METHODS AND RESULTS: Quantitative coronary angiography, intravascular ultrasound with analysis of radiofrequency backscattering, and as an optional assessment, optical coherence tomography (OCT) were performed at baseline and at a 6-month follow-up. Forty-five patients successfully received a single bioresorbable everolimus drug-eluting vascular scaffold. One patient had postprocedural release of myocardial enzyme without Q-wave occurrence; 1 patient with OCT-diagnosed disruption of the scaffold caused by excessive postdilatation was treated 1 month later with a metallic drug-eluting stent. At follow-up, 3 patients declined recatheterization, 42 patients had quantitative coronary angiography, 37 had quantitative intravascular ultrasound, and 25 had OCT. Quantitative coronary angiography disclosed 1 edge restenosis (1 of 42; in-segment binary restenosis, 2.4%). At variance with the ultrasonic changes seen with the first generation of bioresorbable everolimus drug-eluting vascular scaffold at 6 months, the backscattering of the polymeric struts did not decrease over time, the scaffold area was reduced by only 2.0% with intravascular ultrasound, and no change was noted with OCT. On an intention-to-treat basis, the late lumen loss amounted to 0.19±0.18 mm with a limited relative decrease in minimal luminal area of 5.4% on intravascular ultrasound. OCT showed at follow-up that 96.8% of the struts were covered and that malapposition of at least 1 strut, initially observed in 12 scaffolds, was detected at follow-up in only 3 scaffolds. Mean neointimal growth measured by OCT between and on top of the polymeric struts equaled 1.25 mm(2), or 16.6% of the scaffold area. CONCLUSION: Modified manufacturing process of the polymer and geometric changes in the polymeric platform have substantially improved the medium-term performance of this new generation of drug-eluting scaffold to become comparable to those of current drug eluting stents. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov. Unique identifier: NCT00856856.

Four-year clinical follow-up of the XIENCE V everolimus-eluting coronary stent system in the treatment of patients with de novo coronary artery lesions: the SPIRIT II trial.

This report describes the 4-year clinical outcomes of the SPIRIT II study, which randomized 300 patients to treatment with the XIENCE V everolimus-eluting stent (EES), or the TAXUS paclitaxel-eluting stent. At 4-year clinical follow-up, which was available in 256 (85.3%) patients, treatment with EES lead to a trend for lower rates of ischemia-driven major adverse cardiovascular events, a composite of cardiac death, myocardial infarction, and ischemia-driven target lesion revascularization (EES 7.7% vs. paclitaxel-eluting stent 16.4%, P = 0.056). Treatment with EES also resulted in a trend toward lower rates of cardiac death and numerically lower rates of myocardial infarction, ischemia-driven target lesion revascularization, and stent thrombosis. Overall, this study reports numerically fewer clinical events in patients treated with EES at 4-year follow-up, which is consistent with results from earlier follow-up.

A bioabsorbable everolimus-eluting coronary stent system (ABSORB): 2-year outcomes and results from multiple imaging methods.

BACKGROUND: Drug-eluting metallic coronary stents predispose to late stent thrombosis, prevent late lumen vessel enlargement, hinder surgical revascularisation, and impair imaging with multislice CT. We assessed the safety of the bioabsorbable everolimus-eluting stent (BVS). METHODS: 30 patients with a single de-novo coronary artery lesion were followed up for 2 years clinically and with multiple imaging methods: multislice CT, angiography, intravascular ultrasound, derived morphology parameters (virtual histology, palpography, and echogenicity), and optical coherence tomography (OCT). FINDINGS: Clinical data were obtained from 29 of 30 patients. At 2 years, the device was safe with no cardiac deaths, ischaemia-driven target lesion revascularisations, or stent thromboses recorded, and only one myocardial infarction (non-Q wave). 18-month multislice CT (assessed in 25 patients) showed a mean diameter stenosis of 19% (SD 9). At 2-year angiography, the in-stent late loss of 0.48 mm (SD 0.28) and the diameter stenosis of 27% (11) did not differ from the findings at 6 months. The luminal area enlargement on OCT and intravascular ultrasound between 6 months and 2 years was due to a decrease in plaque size without change in vessel size. At 2 years, 34.5% of strut locations presented no discernible features by OCT, confirming decreases in echogenicity and in radiofrequency backscattering; the remaining apparent struts were fully apposed. Additionally, vasomotion occurred at the stented site and adjacent coronary artery in response to vasoactive agents. INTERPRETATION: At 2 years after implantation the stent was bioabsorbed, had vasomotion restored and restenosis prevented, and was clinically safe, suggesting freedom from late thrombosis. Late luminal enlargement due to plaque reduction without vessel remodelling needs confirmation.

An everolimus-eluting stent versus a paclitaxel-eluting stent in small vessel coronary artery disease: a pooled analysis from the SPIRIT II and SPIRIT III trials.

OBJECTIVES: To evaluate the safety and efficacy of the XIENCE V everolimus-eluting stent compared to the TAXUS paclitaxel-eluting stent in small vessels. BACKGROUND: The XIENCE V everolimus-eluting stent (EES) has been shown to improve angiographic and clinical outcomes after percutaneous myocardial revascularization, but its performance in small coronary arteries has not been investigated. METHODS: In this pooled analysis, we studied a cohort of 541 patients with small coronary vessels (reference diameter <2.765 mm) by using patient and lesion level data from the SPIRIT II and SPIRIT III studies. TAXUS Express (73% of lesions) and TAXUS Liberté (27% of lesions) paclitaxel-eluting stents (PES) were used as controls in SPIRIT II. In SPIRIT III, Taxus Express(2) PES was the control. RESULTS: Mean angiographic in-stent and in-segment late loss was significantly less in the EES group compared with the PES group, (0.15 +/- 0.37 mm vs. 0.30 +/- 0.44 mm; P = 0.011 for in-stent; 0.10 +/- 0.38 mm vs. 0.21 +/- 0.34 mm; P = 0.034 for in-segment). EES also resulted in a significant reduction in composite major adverse cardiac events at 1 year (19/366 [5.2%] vs. 17/159 [10.7%]; P = 0.037), due to fewer non-Q-wave myocardial infarctions and target lesion revascularizations. At 1 year, the rate of non-Q-wave myocardial infarction was significantly lower in the EES group compared with that of the PES group (6/366 [1.6%] vs. 8/159 [5.0%]; P = 0.037). CONCLUSIONS: In patients with small vessel coronary arteries, the XIENCE V EES was superior to the TAXUS PES.

Five-year long-term clinical follow-up of the XIENCE V everolimus eluting coronary stent system in the treatment of patients with de novo coronary artery lesions: the SPIRIT FIRST trial.

BACKGROUND: Drug-eluting stents have shown to be superior over bare metal stents in clinical and angiographic outcomes after percutaneous treatment of coronary artery stenosis. However, long-term follow-up data are scarce and only available for sirolimus- and paclitaxel-eluting stents. AIM: To assess the feasibility and performance of the XIENCE V everolimus-eluting stent (EES) versus an identical bare metal stent after a 5-year follow-up period. METHODS: SPIRIT FIRST was a First in Man, multicentre, prospective, single-blind, clinical trial, randomizing 60 patients with a single de novo coronary artery lesion in a ratio of 1:1 to either an everolimus eluting or a bare metal control stent. RESULTS: At 5-year clinical follow-up, data were available in 89% and 86% of patients in the everolimus and control arm, respectively. In the everolimus arm, no additional death, myocardial infarction, clinically driven target lesion revascularization (TLR), or clinically driven target vessel revascularization (TVR) events were observed between 1- and 5-year follow-up. The 5-year hierarchical major adverse cardiac events (MACE) and target vessel failure (TVF) rates for the everolimus arm were 16.7% (4/24) for both endpoints. In the control group, no additional cardiac death, myocardial infarction, or clinically driven TLR events were observed between 2- and 5-year follow-up. No additional clinically driven TVR events were observed between 3- and 5-year follow-up. The 5-year hierarchical MACE and TVF rates for the control arm were 28.0% (7/25) and 36.0% (9/25), respectively. No stent thromboses were observed in either the everolimus arm or the control arm up to 5 years. CONCLUSION: The favorable 5-year long term clinical outcome of the EES is consistent with the results from other studies of the EES with shorter follow-up.

Efficacy of everolimus eluting stent implantation in patients with calcified coronary culprit lesions: two-year angiographic and three-year clinical results from the SPIRIT II study.

BACKGROUND: Little is known about the impact of treatment with drug-eluting stents (DES) on calcified coronary lesions. This analysis sought to assess the safety and efficacy of the XIENCE V everolimus-eluting stent (EES) in patients with calcified or noncalcified culprit lesions. METHODS: The study population consisted of 212 patients with 247 lesions, who were treated with EES alone. Target lesions were angiographically classified as none/mild, moderate, or severe grades of calcification. The population was divided into two groups: those with at least one target lesion moderately or severely calcified (the calcified group: 68 patients with 75 calcified lesions) and those with all target lesions having mild or no calcification (the noncalcified group: 144 patients). Six-month and 2-year angiographic follow-up and clinical follow-up up to 3 years were completed. RESULTS: The baseline characteristics were not significantly different between both groups. When compared with the noncalcified group, the calcified group had significantly higher rates of 6-month in-stent angiographic binary restenosis (ABR, 4.3% vs. 0%, P = 0.03) and ischemia-driven target lesion revascularization (ID-TLR, 5.9% vs. 0%, P = 0.01), resulting in numerically higher major cardiac adverse events (MACE, 5.9% vs. 1.4%, P = 0.09). At 2 years, when compared with the noncalcified group, the calcified group presented higher in-stent ABR (7.4% vs. 0%, P = 0.08) and ID-TLR (7.8% vs. 1.5%, P = 0.03), resulting in numerically higher MACE (10.9% vs. 4.4%, P = 0.12). At 3 years, ID-TLR tended to be higher in the calcified group than in the noncalcified group (8.6% vs. 2.4%, P = 0.11), resulting in numerically higher MACE (12.1% vs. 4.7%, P = 0.12). CONCLUSIONS: The MACE rates in patients treated with EES for calcified lesions were higher than in those for noncalcified lesions, but remained lower than the results of previously reported stent studies. EES implantation in patients with calcified culprit lesions was safe and associated with favorable reduction of restenosis and repeat revascularization. © 2010 Wiley-Liss, Inc.

Systemic exposure of everolimus after stent implantation: a pharmacokinetic study.

OBJECTIVES: We evaluated the pharmacokinetics of the eluted everolimus by assessing systemic drug release and distribution of everolimus-eluting stents. BACKGROUND: Drugs eluted by a coronary stent might cause adverse events such as tumors, infections, or noncardiac death. The systemic exposure of the drugs is unknown because there are only limited data about pharmacokinetics of drug-eluting stents in humans. METHODS: Venous blood samples in a subset of 39 patients were drawn just before implantation of the first stent (baseline, 0-minute time point) and at 10 and 30 minutes and 1, 2, 4, 6, 12, 24, 36, 48, 72, 168, and 720 hours (30 days) after completion of implantation of the last stent. Whole blood concentrations of everolimus were determined using a sensitive validated high-performance liquid chromatography mass spectrometry/mass spectrometry method. RESULTS: The total dose of everolimus received by the patients ranged from 53 to 588 microg. The last time point up to which whole blood concentrations could be quantified ranged per patient from 4 to 720 hours after implantation of the last stent. Across all dose levels, individual T(max) values ranged from 0.13 and 2.17 hours; individual C(max) ranged from 0.14 to 2.79 ng/mL. CONCLUSION: This study confirms the limited exposure to the systemic circulation of the eluted drug with the use of the XIENCE V Everolimus-Eluting Coronary Stent System (Abbott Vascular, Santa Clara, CA). Therefore, a systemic cause of adverse events is unlikely.

Incidence and Potential Mechanism(s) of Post-Procedural Rise of Cardiac Biomarker in Patients With Coronary Artery Narrowing After Implantation of an Everolimus-Eluting Bioresorbable Vascular Scaffold or Everolimus-Eluting Metallic Stent.

OBJECTIVES: This study sought to evaluate the mechanism of post-procedural cardiac biomarker (CB) rise following device implantation. BACKGROUND: A fully bioresorbable Absorb scaffold, compared with everolimus-eluting metallic stents (EES), might be associated with a higher incidence of periprocedural myocardial injury. METHODS: In 501 patients with stable or unstable angina randomized to either Absorb (335 patients) or EES (n = 166) in the ABSORB II trial, 3 types of CB (creatine kinase, creatine kinase-myocardial band, and troponin) were obtained before and after procedure. Per protocol, periprocedural myocardial infarction (PMI) was defined as creatine kinase rise >2× the upper limit of normal with creatine kinase-myocardial band rise. RESULTS: Incidence of side branch occlusion and any anatomic complications assessed by angiography was similar between the 2 treatment arms (side branch occlusion: Absorb: 5.3% vs. Xience: 7.6%, p = 0.07; any anatomic complication: Absorb: 16.4% vs. EES: 19.9%, p = 0.39). Fourteen patients who presented with recent myocardial infarction at entry with normalized creatine kinase-myocardial band according to the protocol were excluded for post-CB analysis. The overall compliance for CB was 97.8%. The CB rise subcategorized in 7 different ranges was comparable between the 2 treatment arms. PMI rate was numerically higher in the Absorb arm according to the per-protocol definitions, and treatment with overlapping devices was the only independent determinant of per-protocol PMI (odds ratio: 5.07, 95% confidence interval: 1.78 to 14.41, p = 0.002). CONCLUSIONS: There were no differences in the incidence of CB rise and PMI between Absorb and EES. Device overlap might be a precipitating factor of myocardial injury. (ABSORB II Randomized Clinical Trial: A Clinical Evaluation to Compare the Safety, Efficacy, and Performance of Absorb Everolimus Eluting Bioresorbable Vascular Scaffold System Against Xience Everolimus Eluting Coronary Stent System in the Treatment of Subjects With Ischemic Heart Disease Caused by De Novo Native Coronary Artery Lesions [ABSORB II]; NCT01425281).

Five-year long-term clinical follow-up of the XIENCE V everolimus-eluting coronary stent system in the treatment of patients with de novo coronary artery disease: the SPIRIT II trial.

AIMS: To assess the safety and performance of the XIENCE V everolimus-eluting stent (EES) versus the TAXUS paclitaxel-eluting stent (PES) in the treatment of patients with de novo coronary artery lesions after a five-year follow-up period. Second-generation drug-eluting stents (DES) were developed with the aim of improving the safety profile of DES, after reports of stent thrombosis (ST) with first-generation devices. However, long-term follow-up data are scarce. METHODS AND RESULTS: SPIRIT II was a multicentre, prospective, single-blind, clinical trial, randomising 300 patients with up to two de novo coronary artery lesions in a ratio of 3:1 to either a EES or a PES. The five-year clinical follow-up was completed in 244 patients (81%). At five-year follow-up, 19.5% of patients were on thienopyridine in the EES arm, while 30.5% were on the same therapy in the PES arm. Cardiac mortality was significantly lower in EES than in PES (1.5% vs. 7.3%, p=0.015). There was a trend towards lower cardiac death and MI (4.8% vs. 11.4%) and lower ID-TLR (4.7% vs. 9.4%) in EES than in PES. As a result, there was a consistent reduction in ID-MACE for EES vs. PES (ID-MACE 8.0% vs. 18.1%, p=0.018). In addition, the ARC-defined stent thrombosis rate was numerically lower in EES compared to PES (0.9% vs. 2.8%). No definite stent thrombosis events were observed after two years in the EES arm. CONCLUSIONS: Five-year clinical follow-up of the SPIRIT II trial demonstrated the continuing long-term safety and efficacy of EES.

The edge vascular response following implantation of the Absorb everolimus-eluting bioresorbable vascular scaffold and the XIENCE V metallic everolimus-eluting stent. First serial follow-up assessment at six months and two years: insights from the first-in-man ABSORB Cohort B and SPIRIT II trials.

AIMS: To assess serially the edge vascular response (EVR) of a bioresorbable vascular scaffold (BVS) compared to a metallic everolimus-eluting stent (EES). METHODS AND RESULTS: Non-serial evaluations of the Absorb BVS at one year have previously demonstrated proximal edge constrictive remodelling and distal edge changes in plaque composition with increase of the percent fibro-fatty (FF) tissue component. The 5 mm proximal and distal segments adjacent to the implanted devices were investigated serially with intravascular ultrasound (IVUS), post procedure, at six months and at two years, from the ABSORB Cohort B1 (n=45) and the SPIRIT II (n=113) trials. Twenty-two proximal and twenty-four distal edge segments were available for analysis in the ABSORB Cohort B1 trial. In the SPIRIT II trial, thirty-three proximal and forty-six distal edge segments were analysed. At the 5-mm proximal edge, the vessels treated with an Absorb BVS from post procedure to two years demonstrated a lumen loss (LL) of 6.68% (-17.33; 2.08) (p=0.027) with a trend toward plaque area increase of 7.55% (-4.68; 27.11) (p=0.06). At the 5-mm distal edge no major changes were evident at either time point. At the 5-mm proximal edge the vessels treated with a XIENCE V EES from post procedure to two years did not show any signs of LL, only plaque area decrease of 6.90% (-17.86; 4.23) (p=0.035). At the distal edge no major changes were evident with regard to either lumen area or vessel remodelling at the same time point. CONCLUSIONS: The IVUS-based serial evaluation of the EVR up to two years following implantation of a bioresorbable everolimus-eluting scaffold shows a statistically significant proximal edge LL; however, this finding did not seem to have any clinical implications in the serial assessment. The upcoming imaging follow-up of the Absorb BVS at three years is anticipated to provide further information regarding the vessel wall behaviour at the edges.

Clinical and intravascular imaging outcomes at 1 and 2 years after implantation of absorb everolimus eluting bioresorbable vascular scaffolds in small vessels. Late lumen enlargement: does bioresorption matter with small vessel size? Insight from the ABSORB cohort B trial.

BACKGROUND: The long-term results after second generation everolimus eluting bioresorbable vascular scaffold (Absorb BVS) placement in small vessels are unknown. Therefore, we investigated the impact of vessel size on long-term outcomes, after Absorb BVS implantation. METHODS: In ABSORB Cohort B Trial, out of the total study population (101 patients), 45 patients were assigned to undergo 6-month and 2-year angiographic follow-up (Cohort B1) and 56 patients to have angiographic follow-up at 1-year (Cohort B2). The pre-reference vessel diameter (RVD) was <2.5 mm (small-vessel group) in 41 patients (41 lesions) and ≥2.5 mm (large-vessel group) in 60 patients (61 lesions). Outcomes were compared according to pre-RVD. RESULTS: At 2-year angiographic follow-up no differences in late lumen loss (0.29±0.16 mm vs 0.25±0.22 mm, p=0.4391), and in-segment binary restenosis (5.3% vs 5.3% p=1.0000) were demonstrated between groups. In the small-vessel group, intravascular ultrasound analysis showed a significant increase in vessel area (12.25±3.47 mm(2) vs 13.09±3.38 mm(2) p=0.0015), scaffold area (5.76±0.96 mm(2) vs 6.41±1.30 mm(2) p=0.0008) and lumen area (5.71±0.98 mm(2) vs 6.20±1.27 mm(2) p=0.0155) between 6-months and 2-year follow-up. No differences in plaque composition were reported between groups at either time point. At 2-year clinical follow-up, no differences in ischaemia-driven major adverse cardiac events (7.3% vs 10.2%, p=0.7335), myocardial infarction (4.9% vs 1.7%, p=0.5662) or ischaemia-driven target lesion revascularisation (2.4% vs 8.5%, p=0.3962) were reported between small and large vessels. No deaths or scaffold thrombosis were observed. CONCLUSIONS: Similar clinical and angiographic outcomes at 2-year follow-up were reported in small and large vessel groups. A significant late lumen enlargement and positive vessel remodelling were observed in small vessels.

Four-year clinical follow-up of the ABSORB everolimus-eluting bioresorbable vascular scaffold in patients with de novo coronary artery disease: the ABSORB trial.

AIM: The first-in-man ABSORB Cohort A trial demonstrated the bioresorption of the ABSORB BVS (Abbott Vascular, Santa Clara, CA, USA) at two years. This report describes the 4-year clinical outcomes. METHODS AND RESULTS: The ABSORB Cohort A trial enrolled 30 patients with a single de novo native coronary artery lesion. Clinical follow-up was available in 29 patients since one patient withdrew consent after the six month follow-up. At four years, the hierarchical ID-MACE of 3.4% remained unchanged. Clopidogrel therapy had been discontinued in all patients. CONCLUSION: Four-year clinical results demonstrate a sustained low MACE rate (3.4%) without any late complications such as stent thrombosis.

Circumferential evaluation of the neointima by optical coherence tomography after ABSORB bioresorbable vascular scaffold implantation: can the scaffold cap the plaque?

OBJECTIVE: To quantify the circumferential healing process at 6 and 12 months following scaffold implantation. BACKGROUND: The healing process following stent implantation consists of tissue growing on the top of and in the space between each strut. With the ABSORB bioresorbable vascular scaffold (BVS), the outer circumference of the scaffold is detectable by optical coherence tomography (OCT), allowing a more accurate and complete evaluation of the intra-scaffold neointima. METHODS: A total of 58 patients (59 lesions), who received an ABSORB BVS 1.1 implantation and a subsequent OCT investigation at 6 (n=28 patients/lesions) or 12 (n=30 patients with 31 lesions) months follow-up were included in the analysis. The thickness of the neointima was calculated circumferentially in the area between the abluminal side of the scaffold and the lumen by means of an automated detection algorithm. The symmetry of the neointima thickness in each cross section was evaluated as the ratio between minimum and maximum thickness. RESULTS: The neointima area was not different between 6 and 12 months follow-up (1.57±0.42 mm(2) vs. 1.64±0.77 mm(2); p=0.691). No difference was also found in the mean thickness of the neointima (median [IQR]) between the two follow-up time points (210 µm [180-260]) vs. 220 µm [150-260]; p=0.904). However, the symmetry of the neointima thickness was higher at 12 than at 6 months follow-up (0.23 [0.13-0.28] vs. 0.16 [0.08-0.21], p=0.019). CONCLUSIONS: A circumferential evaluation of the healing process following ABSORB implantation is feasible, showing the formation of a neointima layer, that resembles a thick fibrous cap, known for its contribution to plaque stability.

Vascular response of the segments adjacent to the proximal and distal edges of the ABSORB everolimus-eluting bioresorbable vascular scaffold: 6-month and 1-year follow-up assessment: a virtual histology intravascular ultrasound study from the first-in-man ABSORB cohort B trial.

OBJECTIVES: This study sought to investigate in vivo the vascular response at the proximal and distal edges of the second-generation ABSORB everolimus-eluting bioresorbable vascular scaffold (BVS). BACKGROUND: The edge vascular response after implantation of the BVS has not been previously investigated. METHODS: The ABSORB Cohort B trial enrolled 101 patients and was divided into B(1) (n = 45) and B(2) (n = 56) subgroups. The adjacent (5-mm) proximal and distal vessel segments to the implanted ABSORB BVS were investigated at either 6 months (B(1)) or 1 year (B(2)) with virtual histology intravascular ultrasound (VH-IVUS) imaging. RESULTS: At the 5-mm proximal edge, the only significant change was modest constrictive remodeling at 6 months (Δ vessel cross-sectional area: -1.80% [-3.18; 1.30], p < 0.05), with a tendency to regress at 1 year (Δ vessel cross-sectional area: -1.53% [-7.74; 2.48], p = 0.06). The relative change of the fibrotic and fibrofatty (FF) tissue areas at this segment were not statistically significant at either time point. At the 5-mm distal edge, a significant increase in the FF tissue of 43.32% [-19.90; 244.28], (p < 0.05) 1-year post-implantation was evident. The changes in dense calcium need to be interpreted with caution since the polymeric struts are detected as "pseudo" dense calcium structures with the VH-IVUS imaging modality. CONCLUSIONS: The vascular response up to 1 year after implantation of the ABSORB BVS demonstrated some degree of proximal edge constrictive remodeling and distal edge increase in FF tissue resulting in nonsignificant plaque progression with adaptive expansive remodeling. This morphological and tissue composition behavior appears to not significantly differ from the behavior of metallic drug-eluting stents at the same observational time points.

Temporal changes of coronary artery plaque located behind the struts of the everolimus eluting bioresorbable vascular scaffold.

Implantation of a coronary stent results in a mechanical enlargement of the coronary lumen with stretching of the surrounding atherosclerotic plaque. Using intravascular ultrasound virtual-histology (IVUS-VH) we examined the temporal changes in composition of the plaque behind the struts (PBS) following the implantation of the everolimus eluting bioresorbable vascular scaffold (BVS). Using IVUS-VH and dedicated software, the composition of plaque was analyzed in all patients from the ABSORB B trial who were imaged with a commercially available IVUS-VH console (s5i system, Volcano Corporation, Rancho Cordova, CA, USA) post-treatment and at 6-month follow-up. This dedicated software enabled analysis of the PBS after subtraction of the VH signal generated by the struts. The presence of necrotic core (NC) in contact with the lumen was also evaluated at baseline and follow-up. IVUS-VH data, recorded with s5i system, were available at baseline and 6-month follow-up in 15 patients and demonstrated an increase in both the area of PBS (2.45 ± 1.93 mm(2) vs. 3.19 ± 2.48 mm(2), P = 0.005) and the external elastic membrane area (13.76 ± 4.07 mm(2) vs. 14.76 ± 4.56 mm(2), P = 0.006). Compared to baseline there was a significant progression in the NC (0.85 ± 0.70 mm(2) vs. 1.21 ± 0.92 mm(2), P = 0.010) and fibrous tissue area (0.88 ± 0.79 mm(2) vs. 1.15 ± 1.05 mm(2), P = 0.027) of the PBS. The NC in contact with the lumen in the treated segment did not increase with follow-up (7.33 vs. 6.36%, P = 0.2). Serial IVUS-VH analysis of BVS-treated lesions at 6-month demonstrated a progression in the NC and fibrous tissue content of PBS.

Serial in vivo intravascular ultrasound-based echogenicity changes of everolimus-eluting bioresorbable vascular scaffold during the first 12 months after implantation insights from the ABSORB B trial.

OBJECTIVES: This study sought to investigate quantitative and homogeneity differential echogenicity changes of the ABSORB scaffold (1.1) during the first year after implantation. BACKGROUND: The imaging of the ABSORB bioresorbable vascular scaffold degradation by intravascular ultrasound (IVUS) has previously demonstrated diminishing gray-level intensity of the struts over time that can be evaluated by IVUS-based differential echogenicity. The first generation of ABSORB (1.0) showed a 50% reduction in hyperechogenicity at 6 months and restoration of the pre-ABSORB implantation values at 2 years. The second generation of ABSORB (1.1), investigated in the ABSORB B trial, was modified to prolong the duration of luminal scaffolding. METHODS: A total of 63 patients were examined by IVUS immediately post-implantation and at 6-month (Cohort B1, n = 28) or 12-month (Cohort B2, n = 35) follow-up. IVUS-based tissue composition analysis software was used to quantify changes in hyperechogenicity over time in the scaffolded regions. Relative changes in hyperechogenicity were calculated as: 100 × (% hyperechogenicity at follow-up - % hyperechogenicity at baseline)/% hyperechogenicity at baseline. RESULTS: At 6- and 12-month follow-up, there was a 15% (from 22.58 ± 9.77% to 17.42 ± 6.69%, p = 0.001) and 20% (from 23.51 ± 8.57% to 18.25 ± 7.19%, p < 0.001) reduction in hyperechogenicity, respectively, compared with post-implantation values. No difference in hyperechogenicity changes were observed between the proximal, medial, or distal part of the scaffolded segment. CONCLUSIONS: Quantitative differential echogenicity changes of the ABSORB scaffold (1.1) during the first 12 months after implantation are lower compared with those previously observed with its first generation (1.0), confirming the value of the manufacturing changes and suggesting a slower degradation rate of the scaffold.

A pooled gender based analysis comparing the XIENCE V(R) everolimus-eluting stent and the TAXUS paclitaxel-eluting stent in male and female patients with coronary artery disease, results of the SPIRIT II and SPIRIT III studies: two-year analysis.

AIMS: To assess the safety and efficacy of the XIENCE V everolimus-eluting stent (EES) compared to the TAXUS paclitaxel-eluting stent (PES) in women at two years. METHODS AND RESULTS: In this pooled analysis, a cohort of 395 women and 906 men was studied by using patient level and lesion level clinical data from SPIRIT II and SPIRIT III studies. Women enrolled in these two studies had higher demographic and lesion risk characteristics than their male counterparts. In-stent and in-segment late loss (LL) was significantly less in the women in the EES group compared to the women in the PES group (in-stent 0.15+/-0.44 mm vs. 0.45+/-0.51 mm; P<0.01, in-segment 0.09+/-0.46 mm vs. 0.29+/-0.40 mm; P<0.01). In women, EES compared to PES resulted in significant reductions in major adverse cardiac events (MACE) (8.5% vs 16.4%; p=0.02) and in target vessel failure (TVF) (11.2% vs 19.5%; p=0.02) at two years. In men, a significant difference was seen in in-stent LL and in-stent % diameter stenosis (DS) favouring EES (in-stent LL 0.14+/-0.33 mm vs. 0.28+/-0.47 mm; P<0.01, in-stent %DS 9.28+/-13.86 vs. 13.64+/-18.31; P<0.01). MACE rates at two years were lower in males treated with EES compared to PES (6.7% vs. 10.9%; p=0.03). The interaction between gender and stent type was not found to be significant for MACE at two years. CONCLUSIONS: In this pooled analysis of two randomised trials, at two years, EES compared to PES resulted in reduced angiographic LL, fewer MACE and TVF events in women and reduced angiographic LL and %DS and fewer MACE events in men.

Clinical follow-up 3 years after everolimus- and paclitaxel-eluting stents: a pooled analysis from the SPIRIT II (A Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Patients With De Novo Native Coronary Artery Lesions) and SPIRIT III (A Clinical Evaluation of the Investigational Device XIENCE V Everolimus Eluting Coronary Stent System [EECSS] in the Treatment of Subjects With De Novo Native Coronary Artery Lesions) randomized trials.

OBJECTIVES: The purpose of this study was to investigate long-term 3-year clinical outcomes of an everolimus-eluting stent (EES) versus a paclitaxel-eluting stent (PES). BACKGROUND: Compared with PES, EES reduced target vessel failure and major adverse cardiac events at 2 years. Whether the benefits of EES are sustained at 3 years has not been reported. METHODS: In the SPIRIT II (A Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Patients With De Novo Native Coronary Artery Lesions) and SPIRIT III (A Clinical Evaluation of the Investigational Device XIENCE V Everolimus Eluting Coronary Stent System [EECSS] in the Treatment of Subjects With De Novo Native Coronary Artery Lesions) trials, 1,302 patients were randomly assigned to EES (n = 892) or PES (n = 410). We report the 3-year clinical follow-up of this patient-level pooled analysis. RESULTS: At 3 years, EES compared with PES resulted in a significant reduction in myocardial infarction (3.8% vs. 6.7%; relative risk [RR]: 0.56; 95% confidence interval [CI]: 0.34 to 0.94; p = 0.04), and target lesion revascularization (6.8% vs. 12.7%; RR: 0.53; 95% CI: 0.37 to 0.77; p = 0.001). Everolimus-eluting stents resulted in a significant reduction in target vessel failure (13.7% vs. 19.5%; RR: 0.70; 95% CI: 0.54 to 0.92; p = 0.01), and major adverse cardiac events (9.1% vs. 16.3%; RR: 0.56; 95% CI: 0.41 to 0.76; p = 0.0004). The cumulative rates of Academic Research Consortium-defined definite or probable stent thrombosis were 1.2% in EES patients and 1.9% in PES patients (RR: 0.64; 95% CI: 0.25 to 1.68; p = 0.43). CONCLUSIONS: In this patient-level pooled analysis, EES compared with PES resulted in a significant and persistent reduction in target vessel failure and major adverse cardiac events at 3 years due to fewer myocardial infarction and ischemic target lesion revascularization events, which is consistent with superior safety and efficacy of the EES platform.

Monitoring in vivo absorption of a drug-eluting bioabsorbable stent with intravascular ultrasound-derived parameters a feasibility study.

OBJECTIVES: The aim of this study was to investigate the feasibility of using quantitative differential echogenicity to monitor the in vivo absorption process of a drug-eluting poly-l-lactic-acid (PLLA) bioabsorbable stent (BVS, Abbott Vascular, Santa Clara, California). BACKGROUND: A new bioabsorbable, balloon-expanded coronary stent was recently evaluated in a first-in-man study. Little is known about the absorption process in vivo in diseased human coronary arteries. METHODS: In the ABSORB (Clinical Evaluation of the BVS everolimus eluting stent system) study, 30 patients underwent treatment with the BVS coronary stent system and were examined with intracoronary ultrasound (ICUS) after implantation, at 6 months and at 2-year follow-up. Quantitative ICUS was used to measure dimensional changes, and automated ICUS-based tissue composition software (differential echogenicity) was used to quantify plaque compositional changes over time in the treated regions. RESULTS: The BVS struts appeared as bright hyperechogenic structures and showed a continuous decrease of their echogenicity over time, most likely due to the polymer degradation process. In 12 patients in whom pre-implantation ICUS was available, at 2 years the percentage-hyperechogenic tissue was close to pre-implantation values, indicating that the absorption process was either completed or the remaining material was no longer differentially echogenic from surrounding tissues. CONCLUSIONS: Quantitative differential echogenicity is a useful plaque compositional measurement tool. Furthermore, it seems to be valuable for monitoring the absorption process of bioabsorbable coronary stents made of semi-crystalline polymers.