2.1

Registry objective

The registry collects prospective data regarding the quality of care with the use of the ABSORB BVS for coronary revascularization, including the following specific objectives:

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  Documentation of all consecutive patients having been treated with the ABSORB BVS system under clinical real-world conditions

  
  
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  Documentation of indications, procedural results, and short- and long-term outcomes

  
  
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  Documentation of the technical performance of ABSORB implantation procedures

  
  
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  Collection of safety data, in particular documentation of in-hospital mortality, major non-fatal complications (especially myocardial infarction, re-PCI or coronary artery bypass graft surgery (CABG), and scaffold thrombosis)

  
  
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  Documentation of long-term patient safety characterized by mortality and major non-fatal complications (especially myocardial infarction, re-PCI or CABG, and thrombosis) at discharge from hospital and at 30 days, 6 months, 2 years, and 5 years after the procedure

  
  
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  Gathering of data on the quality of life (QoL) pre- and post-ABSORB implantation to document individual QoL dimensions as well as individual symptoms

  
  
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  Gathering of health economics data (capture of direct costs, especially with respect to change of medication and outpatient/inpatient hospital services, and indirect costs) pre- and post-ABSORB ^™ implantation

2.2

Registry design

The German–Austrian ABSORB Registry (ClinicalTrials.gov: NCT02066623 ) is a prospective, non-interventional, multicenter, clinical follow-up study of consecutive patients with significant coronary artery stenosis who have been treated with the everolimus-eluting ABSORB BVS. The registry is an observational study, and a patient’s participation in this trial has no impact on his or her indication for diagnostics, coronary angiography, or therapy. Patients are treated in compliance with currently valid instructions for use as well as medical society guidelines and the hospital’s internal directives. Drug therapy is designed to meet medical society guidelines or the clinic’s internal directives.

2.3

The ABSORB BVS system

The circumferential and cross-linked struts of the ABSORB BVS are made of poly-,L-lactic acid (PLLA) with a thickness of 150 μm. The ABSORB BVS elutes a 1:1 mixture of poly-D,L-lactic acid and the antiproliferative drug everolimus. To provide visualization, radiopaque markers are located at a distance of 0.3 mm to 1.1 mm from either end. Complete resorption of the current generation of ABSORB BVS was observed after approximately 3 years in animal models . Systematic information of the time to complete dissolution in humans is sparse and can only be assumed to be comparable to that in animals.

Implantation of the ABSORB BVS is followed by a series of restructuring processes that finally lead to the scaffold being completely resorbed. In the early phase, the polymers absorb fluids from the luminal blood and the surrounding tissue. Long-chain polymers are hydrolyzed to short-chain polymers, resulting in fragmentation of the scaffold struts and loss of radial strength. Finally, the polymer microparticles are restructured and resorbed, resulting in L-lactate being degraded via pyruvate and citric acid cycle to CO ₂ and H ₂ O. The degradation process of the polymer scaffold depends on the length of the polymer chains (molecular weight) and the hydrophilic characteristics of the polymers.

2.4

Number of patients and duration of the registry

All patients at the participating centers in Germany and Austria who have been implanted with the ABSORB BVS are to be included in the registry. Starting in November 2013, a minimum of 5000 patients from about 100 study sites in Austria and Germany will have been enrolled. Participation in the registry is offered to all study sites in Germany and Austria implanting the ABSORB BVS. Participating sites have committed to consecutively enroll in the registry all patients meeting the inclusion criteria. The one and only inclusion criterion for admission of a patient to GABI-R is his or her individual clinical indication for at least one ABSORB™ BVS implant. The only exclusion criterion is a patient’s refusal to sign the informed consent form, i.e. his or her explicit wish not to participate in this registry.

Since it is known that a positive correlation between strut thickness and flow disturbances exists and that this relationship carries negative clinical consequences such as higher restenosis and target vessel revascularization rates after implantation of ABSORB™ BVS, dual anti-platelet therapy is recommended for 12 months.

Clinical events are recorded during hospitalization and in the follow-up period (minimum of 5 years) in terms of the number and time of occurrence of serious adverse cardiac events. Follow-up is to be conducted centrally for all sites by the “Institut für Herzinfarktforschung GmbH” (IHF, Ludwigshafen, Germany), which will analyze all data sets in a manner that is independent of any sponsor. At 30 days, 6 months, 2 years, and 5 years, patients will be notified in writing via mail and asked to fill out “Follow-Up” and the “Quality of Life” questionnaires and to return them to the IHF. If there is no reply, standardized interviews with the patients will be conducted over the phone. If it is not possible to reach a patient, the local residents’ registration office will be contacted. Participating study sites are free to document any additional patient visits within 5 years from the index hospital stay (e.g. in case of repeat hospitalization).

2.5

Target parameters

Major adverse cardiac events (MACEs) comprise cardiac death, any myocardial infarction, and clinically driven percutaneous or surgical target lesion revascularization. Target vessel failure (TVF) includes cardiac death, target vessel myocardial infarction, and clinically driven percutaneous or surgical target vessel revascularization (TVR). Target lesion failure (TLF) includes cardiac death, target vessel myocardial infarction, and clinically driven percutaneous or surgical target lesion revascularization (TLR). Scaffold thrombosis is defined as definite, probable, or possible according to the Academic Research Consortium (ARC) criteria.

The procedural outcome of ABSORB BVS implantation will be assessed based on the following parameters: technical success (if the residual stenosis is less than 30% in the scaffold-covered lesion segment at the end of the procedure based on visual estimation), therapy success (technical success without peri-procedural complication), and clinical success (therapy success and no serious MACE). Criteria of quality are TIMI flow pre- and post-implantation and sudden occlusion of a side branch in the case of bifurcation stenosis.

The effectiveness of the ABSORB BVS implant and quality of life following scaffold implantation will be assessed based on the following parameters: angina pectoris score (including CCS score), heart failure score (NYHA), and the results of standardized questionnaires for QoL (EQ 5D) and health-related QoL of patients with coronary artery disease (Seattle Angina Questionnaire, SAQ). Furthermore, consumption of ambulant and stationary resources will be documented for the purpose of health-related economic evaluations.

2.6

Data collection and privacy

Data are collected electronically and centralized by IHF via an internet-based application. Completeness, plausibility, and edit checks are immediately performed when the data are entered, thus widely reducing the necessity for queries.

All data are transmitted using SSL-encrypted methods and stored on the server provided by IHF. Following the completion of the 30-day, 6-month, 2-year, and 5-year follow-up assessments, IHF will transmit the pseudonymized health economics and QoL data to the Chair of Medical Management at the University of Duisburg-Essen for analysis. After complete anonymization of the patients (deletion of patient and study site ID as well as date of birth and intervention) the final database may also be made available to Abbott Vascular Deutschland GmbH, the manufacturer of the ABSORB BVS system. The application for data collection functions with Internet Explorer (version 8), Mozilla Firefox, Google Chrome, or Safari in their current versions. Each participating study site may register any number of users to gain access to the captured data via password.

The patients’ contact data will be maintained separately from their medical data so that follow-up interviews can be conducted by phone. Only those persons responsible for telephone follow-up assessments are granted access to a patient’s address. For statistical analysis, a patient’s medical data will be used in pseudonym form. The IHF commits to complying with Austrian and German data protection legislation and to use the data collected and transmitted by this registry for no other than the indicated purposes. Random spot-checks by a monitor provided by the IHF will be carried out in order to compare genuine data with documented data in the registry’s database.

GABI-R was established and is being conducted according to the Declaration of Helsinki. The patients receive and must sign a written consent form before being included. This investigation was approved by the ethics board of the University of Giessen, Germany (AZ:190/13) and has been registered with clinicaltrials.gov (NCT02066623).

2.7

Statistical methods

The nature of the registry is purely descriptive. Descriptive statistics will be generated with respect to population, applied therapy method, and clinical outcome. To obtain meaningful data, it is mandatory that the participating study sites consecutively enroll in the registry all patients with a clinical indication for ABSORB BVS implantation.

All collected parameters will be evaluated in a descriptive manner. Qualitative data will be analyzed as absolute values and percentages, while continuous variables will be described by descriptive statistics such as means with standard deviation, medians with quartiles, range (min, max), and number of measurements. Data from events during the follow-up period will be depicted using Kaplan–Meier estimates and plots. Cox regression models will be used for identifying independent predictors of the different target parameters. Additionally, analyses in pre-specified subgroups, e.g. regarding indications, co-morbidities, or coronary status, will be performed. Statistical evaluations of health economics and quality of life (EQ5D and SAQ) data will be performed by a cooperating institute, the Chair of Medical Management at the University of Duisburg-Essen.

During the duration of the registry, participating sites will receive benchmarking reports at regular intervals. Reports will be generated individually for each participating study site and each report will compare the study site’s data with those of the other sites. The analysis will include any data collected from the patients enrolled regarding clinical characteristics, therapy, and outcome. This benchmarking system will enable the participating study sites to perform internal and external quality control.