Three-Year Outcomes With the Absorb Bioresorbable Scaffold: Individual-Patient-Data Meta-Analysis From the ABSORB Randomized Trials.

BACKGROUND: The Absorb bioresorbable vascular scaffold (BVS) completely resorbs within 3 years after coronary artery implantation. The safety and effectiveness of BVS through this critical 3-year period have not been characterized. METHODS: We performed an individual-patient-data pooled meta-analysis of the 4 randomized ABSORB trials in which 3389 patients with coronary artery disease were randomly assigned to everolimus-eluting Absorb BVS (n=2164) or cobalt-chromium everolimus-eluting stents (n=1225). The primary efficacy outcome measure was target lesion failure (cardiac mortality, target vessel myocardial infarction, or ischemia-driven target lesion revascularization), and the primary safety outcome measure was device thrombosis. RESULTS: BVS compared with cobalt-chromium everolimus-eluting stents resulted in higher 3-year rates of target lesion failure (11.7% versus 8.1%; risk ratio [RR], 1.38; 95% confidence interval [CI], 1.10-1.73; P=0.006), driven by greater target vessel myocardial infarction (7.8% versus 4.2%; RR, 1.72; 95% CI, 1.26-2.35; P=0.0006) and ischemia-driven target lesion revascularization (6.6% versus 4.4%; RR, 1.44; 95% CI, 1.05-1.98; P=0.02), with comparable cardiac mortality (1.1% versus 1.1%; RR, 0.93; 95% CI, 0.47-1.88; P=0.85). Device thrombosis rates through 3 years were also higher with BVS (2.4% versus 0.6%; RR, 3.71; 95% CI, 1.70-8.11; P=0.001). Between 1 and 3 years, target lesion failure rates (6.1% versus 3.9%; P=0.02) and device thrombosis rates (1.1% versus 0.0%; P<0.0001) were higher with BVS than cobalt-chromium everolimus-eluting stents. CONCLUSIONS: In the present individual-patient-data pooled meta-analysis of the ABSORB trials, BVS was associated with increased rates of target lesion failure and device thrombosis between 1 and 3 years and cumulatively through 3 years of follow-up compared with everolimus-eluting stents. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifiers: NCT01751906, NCT01844284, NCT01923740, and NCT01425281.

Efficacy and Safety of the Absorb Bioresorbable Vascular Scaffold in Females and Males: Results of an Individual Patient-Level Pooled Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: Because females are under-represented in coronary trials, this study sought to assess the relative safety and efficacy of Absorb bioresorbable vascular scaffold (BVS) (Abbott Vascular, Santa Clara, California) and the Xience everolimus-eluting stent in females compared with males. BACKGROUND: The Absorb everolimus-eluting BVS provides drug delivery and mechanical support similar to a metallic drug-eluting stent, followed by resorption and restoration of more normal vascular structure with the potential to improve late clinical outcomes. METHODS: The ABSORB II, ABSORB III, ABSORB Japan, and ABSORB China trials were pooled. Baseline clinical, angiography, procedural variables, and 2-year outcomes were analyzed by sex and device. RESULTS: Among 3,384 randomized patients, 932 (27.5%) were female. Females were older, more often had diabetes and hypertension, but had less everolimus-eluting stent, 3-vessel disease, and smoking compared with males (all p≤0.001). The 2-year rates of target lesion failure with BVS versus everolimus-eluting stent in females were 8.9% versus 6.2% (study-level adjusted hazard ratio: 1.47; 95% confidence interval [CI]: 0.88 to 2.46) and 8.9% versus 6.4% in males (HR: 1.40; 95% CI: 1.02 to 1.92; pinteraction = 0.85). There were no significant interactions between sex and device type for any of the components of target lesion failure. CONCLUSIONS: The relative treatment effects of BVS and everolimus-eluting stent for the 2-year rates of target lesion failure and other cardiovascular outcomes were consistent in females and males.

Efficacy and Safety of the Absorb Everolimus-Eluting Bioresorbable Scaffold for Treatment of Patients With Diabetes Mellitus: Results of the Absorb Diabetic Substudy.

OBJECTIVES: The study sought to evaluate the efficacy and safety of the Absorb everolimus-eluting bioresorbable vascular scaffold (BVS) (Abbott Vascular, Abbott Park, Illinois) in patients with diabetes mellitus. BACKGROUND: Randomized, controlled trials have demonstrated comparable clinical outcomes following percutaneous coronary intervention with either Absorb BVS or metallic Xience everolimus-eluting stent. However, these trials lack power required to provide reliable treatment effect estimates in this high-risk population. METHODS: In a pre-specified, powered analysis, patients with diabetes who received ≥1 Absorb were pooled from the ABSORB II, III, and JAPAN randomized trials and from the single arm ABSORB EXTEND registry. The study composite primary endpoint was target lesion failure (TLF) at 1 year following Absorb BVS compared with a performance goal of 12.7%. RESULTS: Among 754 diabetic patients included in analysis (27.3% insulin treated), the 1-year TLF rate was 8.3% (upper 1-sided 95% confidence limit: 10.1%; p = 0.0001 vs. performance goal). Scaffold thrombosis (definite or probable) was observed in 2.3% of patients. Multivariable regression identified older age, insulin treatment, and smaller pre-procedure reference vessel diameter as significant independent predictors of 1-year TLF. CONCLUSIONS: The Absorb diabetic substudy suggests efficacy and safety of the Absorb BVS for treatment of patients with diabetes mellitus.

Efficacy and Safety of the Absorb Everolimus-Eluting Bioresorbable Scaffold for Treatment of Patients With Diabetes Mellitus: Results of the Absorb Diabetic Substudy

OBJECTIVES The study sought to evaluate the efficacy and safety of the Absorb everolimus-eluting bioresorbable vascular scaffold (BVS) (Abbott Vascular, Abbott Park, Illinois) in patients with diabetes mellitus.BACKGROUND Randomized, controlled trials have demonstrated comparable clinical outcomes following percutaneous coronary intervention with either Absorb BVS or metallic Xience everolimus-eluting stent. However, these trials lack power required to provide reliable treatment effect estimates in this high-risk population.METHODS In a pre-specified, powered analysis, patients with diabetes who received $1 Absorb were pooled from the ABSORB II, III, and JAPAN randomized trials and from the single arm ABSORB EXTEND registry. The study composite primary endpoint was target lesion failure (TLF) at 1 year following Absorb BVS compared with a performance goal of 12.7%.RESULTS Among 754 diabetic patients included in analysis (27.3% insulin treated), the 1-year TLF rate was8.3% (upper 1-sided 95% confidence limit: 10.1%; p » 0.0001 vs. performance goal). Scaffold thrombosis(definite or probable) was observed in 2.3% of patients. Multivariable regression identified older age, insulin treatment, and smaller pre-procedure reference vessel diameter as significant independent predictors of 1-year TLF.CONCLUSIONS The Absorb diabetic substudy suggests efficacy and safety of the Absorb BVS for treatment of patients with diabetes mellitus.

A Three-Gene Assay for Monitoring Immune Quiescence in Kidney Transplantation.

Organ transplant recipients face life-long immunosuppression and consequently are at high risk of comorbidities. Occasionally, kidney transplant recipients develop a state of targeted immune quiescence (operational tolerance) against an HLA-mismatched graft, allowing them to withdraw all immunosuppression and retain stable graft function while resuming immune responses to third-party antigens. Methods to better understand and monitor this state of alloimmune quiescence by transcriptional profiling may reveal a gene signature that identifies patients for whom immunosuppression could be titrated to reduce patient and graft morbidities. Therefore, we investigated 571 unique peripheral blood samples from 348 HLA-mismatched renal transplant recipients and 101 nontransplant controls in a four-stage study including microarray, quantitative PCR, and flow cytometry analyses. We report a refined and highly validated (area under the curve, 0.95; 95% confidence interval, 0.92 to 0.97) peripheral blood three-gene assay (KLF6, BNC2, CYP1B1) to detect the state of operational tolerance by quantitative PCR. The frequency of predicted alloimmune quiescence in stable renal transplant patients receiving long-term immunosuppression (n=150) was 7.3% by the three-gene assay. Targeted cell sorting of peripheral blood from operationally tolerant patients showed a significant shift in the ratio of circulating monocyte-derived dendritic cells with significantly different expression of the genes constituting the three-gene assay. Our results suggest that incorporation of patient screening by specific cellular and gene expression assays may support the safety of drug minimization trials and protocols.

Mapping novel immunogenic epitopes in IgA nephropathy.

BACKGROUND AND OBJECTIVES: IgA plays a key role in IgA nephropathy (IgAN) by forming immune complexes and depositing in the glomeruli, leading to an inflammatory response. However, the antigenic targets and functional characterization of IgA have been incompletely defined in this disease. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study was performed in sera from patients who were studied as part of a prospective, observational study of IgAN. These patients (n=22) all had biopsy-proven IgAN within 3 years of study initiation, complete clinical data, annual urinary inulin clearance for GFRs, and at least 5 years of follow-up. Progression was defined as loss of >5 ml/min per 1.73 m(2) per year of inulin clearance measured over at least 5 years. A protein microarray was used for detection of IgAN-specific IgA autoantibodies in blood across approximately 9000 human antigens to specifically identify the most immunogenic protein targets that drive IgA antibodies in IgAN (n=22), healthy controls (n=10), and non-IgAN glomerular diseases (n=17). Results were validated by ELISA assays in sera and by immunohistochemistry in IgAN kidney biopsies. IgA-specific antibodies were correlated with clinical and histologic variables to assess their effect on disease progression and prognosis. RESULTS: Fifty-four proteins mounted highly significant IgA antibody responses in patients with IgAN with a false discovery rate (q value) of ≤10%; 325 antibodies (P≤0.05) were increased overall. Antitissue transglutaminase IgA was significantly elevated in IgAN (P<0.001, q value of 0%). IgA antibodies to DDX4 (r=-0.55, P=0.01) and ZADH2 (r=-0.48, P=0.02) were significantly correlated with the decline of renal function. Specific IgA autoantibodies are elevated in IgAN compared with normal participants and those with other glomerular diseases. CONCLUSIONS: In this preliminary study, IgA autoantibodies target novel proteins, highly expressed in the kidney glomerulus and tubules. These IgA autoantibodies may play important roles in the pathogenesis of IgAN.

Top five craniofacial techniques for training in plastic surgery residency.

BACKGROUND: Despite increasing specialization of craniofacial surgery, certain craniofacial techniques are widely applicable. The authors identified five such craniofacial techniques and queried American Society of Plastic Surgeons members and plastic surgery program directors regarding their comfort level with the procedures and their opinion on resident training for these selected procedures. METHODS: First, a select group of senior craniofacial surgeons discussed and agreed on the top five procedures. Second, active American Society of Plastic Surgeons were surveyed regarding their opinion on training and their comfort level with each procedure. Third, plastic surgery residency program directors were studied to see which of the top five procedures are taught as part of the plastic surgery residency curriculum. RESULTS: The top five widely applicable craniofacial procedures are technically described and include the following: (1) cranial or iliac bone graft for nasal reconstruction, (2) perialar rim bone graft, (3) lateral canthopexy, (4) osseous genioplasty, and (5) bone graft harvest for orbital floor defects. For practicing plastic surgeons, comfort level in all procedures increased with advancing years in practice (except those with <5 years). A majority of plastic surgeons (>75 percent), especially those with craniofacial fellowship training, felt competent in all procedures except osseous genioplasty (53 percent). Plastic surgery program directors agreed that all top five procedures should be mastered by graduation. CONCLUSIONS: Although program directors felt that all five selected craniofacial procedures should be taught and mastered during residency training, plastic surgeons without craniofacial fellowship training were less comfortable with the techniques. Residency training goals should include competence in core craniofacial techniques.