Coated stents to prevent restenosis in coronary heart disease

Background: In-stent-restenosis (ISR) is considered to be an essential limiting factor of stenting in coronary heart disease (CHD). The development of coated stents has raised expectations on substantial lowering restenosis after stenting with decreasing the rate of restenosis and a reduction in the rate of clinical events. Objectives: The present analysis addresses the questions on medical effectiveness and cost-effectiveness of the use of various coated stent types in CHD. Methods: The literature was searched in December 2004 in the most relevant medical and economic databases. The medical evaluation was conducted on the basis of published RCT. The data from the studies regarding various angiographic, sonographic and clinical endpoints were checked for methodical quality and summarised in meta-analyses. Within the scope of economic evaluation the primary studies were analysed and modelling was performed, applying clinical effect estimates from the meta-analyses of the medical evaluation and current estimates of German costs. Results: Medical evaluation: Ten different stenttypes were used in the included 26 RCT. The results for heparin, silicon-carbide, carbon and PTFE coated stenttypes could not reveal any significant differences between the medical effectiveness of coated and uncoated stents. The application of sirolimus, paclitaxel, everolimus and 7-hexanoyltaxol eluting stents showed a significant lower restenosis at 6-9 months with decrease in the rate of restenosis for polymer-based sirolimus, paclitaxel and 7-hexanoyltaxol eluting stents. In contrast, the use of gold-coated and actinomycin-D eluting stents was associated with a significantly higher restenosis. The polymer-based sirolimus and paclitaxel eluting stents also showed a significant and considerable reduction in the rate of repeated percutaneous revascularisations at 6-12 months (3.5% vs. 19.7%; p<0.0001, RR=0.19 [95%CI: 0.11; 0.33] and 3.5% vs. 12.2%; p<0.0001, RR=0.30 [95%CI: 0.20; 0.43]) and an equivalent reduction in the rate of combined events. The 7-hexanoyltaxol-eluting stents caused, however, a significant increase of stent thrombosis as well as of myocardial infarctions. Economic evaluation: The allocation to polymer-based sirolimus and paclitaxel eluting stents resulted in incremental costs (compared with uncoated stents) of approximately 1,421 € and 1,234 € per patient, taking in account expected revascularisations during the first year after implantation. The mean incremental cost-effectiveness-ratios per avoided revascularisation was 8,881 € and 13,711 €, respectively. The "break-even"-prices for these stenttypes in the used model were 707 € and 551 €, and the "break-even"-risks for ISR after stenting with uncoated stent, was 76% and 65%, respectively. The use of the other evaluated coated stents seems not to be cost-effective. Discussion: The absolute effects and cost savings for patient groups with a higher risk of restenosis could be considerably higher than for patient groups with a lower risk of restenosis. The transferability of the results from the present analysis to other (sub)-populations and technology modifications is limited. The direct comparability of the results for sirolimus and paclitaxel eluting stents is also restricted. Conclusions: From a medical point of view the use of polymer-based sirolimus or paclitaxel eluting stents can be recommended. The use of gold coated, 7-hexanoyltaxol and actinomycin-D eluting stents is in contrast not recommendable. From an economical point of view and on the basis of current stent prices the polymer-based eluting sirolimus and paclitaxel stents should primarily be recommended for patients with a higher risk of restenosis

Drug-eluting stents vs. coronary artery bypass-grafting in coronary heart disease

Background: Coronary artery bypass graft (CABG) and percutaneous revascularisations with implantation of drug-eluting stents (DES) are important treatment methods in coronary heart disease (CHD). Research questions: The evaluation addresses questions on medical efficacy, health economic parameters as well as ethic, social and legal implications in the use of DES vs. CABG in CHD patients. Methods: A systematic literature search was conducted in December 2006 in the most important electronic databases beginning from 2004. Register data and controlled clinical studies were included in the evaluation. Additionally, a health economic modelling was conducted. Results: Medical evaluation: The literature search yielded 2,312 hits. 14 publications about six controlled clinical studies and five publications about two registers were included into the evaluation. Register data showed low mortality (0.2% to 0.7%) and low rates of myocardial infarction (0.5% to 1.4%) during hospital stay. In patients with stenosis of the left anterior descending coronary artery one study showed in several analyses a significantly higher rate of reinterventions and a significantly higher rate of repeated angina pectoris for DES up to two years after the implantation (16.8% vs. 3.6% and 35% vs. 8%). In patients with left main coronary artery stenosis two studies revealed a significantly higher survival without myocardial infarction and stroke for DES up to one year (96% vs. 79% and 95% vs. 91%) and two studies a significantly higher rate of revascularisations up to two years (20% vs. 4% and 25% vs. 5%) after the primary intervention. In patients with multivessel disease, one study found a significantly higher mortality and myocardial infarction rate for CABG at one year (2.7% vs. 1.0% and 4.2% vs. 1.3%). The rate of revascularisations was significantly higher in two studies up to two years after DES implantation (8.5% vs. 4.2% and 14.2% vs. 5.3%). The rate at repeated angina pectoris was significantly higher in one study in DES patients during two-years follow-up (28% vs. 12%). Health economic evaluation: The one-year total costs per patient after CABG were calculated to be 13,373 euro and after DES 10,443 euro, leading to a difference of 2,930 euro in favour of DES implantation. The three-year total costs per patient after CABG were estimated to be 13,675 euro and after DES 10,989 euro, showing a cost difference of 2,686 euro in favour of DES implantation. In the performed sensitivity analyses no break even point was reached. Discussion: Existing data should be viewed only as limited evidence for possible medical and health economic effects. Conclusions: There is limited evidence for the possible advantage of DES vs. CABG with respect to mortality and the rate of myocardial infarction in some indications as well as disadvantages with regard to the rate of revascularisations and the rate of repeated angina pectoris. Moreover there is also a limited evidence for possible economic advantage of DES vs. CABG in multivessel disease. Existing data should be proven in long-term follow-up and in randomised studies

Intravascular brachytherapy for peripheral vascular disease

Scientific background: Percutaneous transluminal angioplasties (PTA) through balloon dilatation with or without stenting, i.e. vessel expansion through balloons with or without of implantation of small tubes, called stents, are used in the treatment of peripheral artery occlusive disease (PAOD). The intravascular vessel irradiation, called intravascular brachytherapy, promises a reduction in the rate of repeated stenosis (rate of restenosis) after PTA. Research questions: The evaluation addresses questions on medical efficacy, cost-effectiveness as well as ethic, social and legal implications in the use of brachytherapy in PAOD patients. Methods: A systematic literature search was conducted in August 2007 in the most important medical electronic databases for publications beginning from 2002. The medical evaluation included randomized controlled trials (RCT). The information synthesis was performed using meta-analysis. Health economic modeling was performed with clinical assumptions derived from the meta-analysis and economical assumptions derived from the German Diagnosis Related Groups (G-DRG-2007). Results: Medical evaluation: Twelve publications about seven RCT on brachytherapy vs. no brachytherapy were included in the medical evaluation. Two RCT showed a significant reduction in the rate of restenosis at six and/or twelve months for brachytherapy vs. no brachytherapy after successful balloon dilatation, the relative risk in the meta-analysis was 0.62 (95% CI: 0.46 to 0.84). At five years, time to recurrence of restenosis was significantly delayed after brachytherapy. One RCT showed a significant reduction in the rate of restenosis at six months for brachytherapy vs. no brachytherapy after PTA with optional stenting, the relative risk in the meta-analysis was 0.76 (95% CI: 0.61 to 0.95). One RCT observed a significantly higher rate of late thrombotic occlusions after brachytherapy in the subgroup of stented patients. A single RCT for brachytherapy vs. no brachytherapy after stenting did not show significant results for the rate of restenosis at six months. Both, early and late thrombotic occlusions appeared more frequently in the brachytherapy group. Health economic evaluation: Additional costs of brachytherapy were estimated to be 1,655 or 1,767 Euro according to the used G-DRG. The incremental cost-effectiveness ratio per avoided restenosis was calculated to be 8,484 Euro or 9,058 Euro for brachytherapy use after successful balloon dilatation, 19,027 Euro or 20,314 Euro for brachytherapy after PTA with optional stenting and -39,646 Euro or -48,330 Euro for brachytherapy after stenting. Discussion: Partially poor performing and reporting quality of the RCT exacerbate the interpretation and the transferability of the study results. The used methodical approach enables the highest evidence level for the determined results and presents a good approximation of the current brachytherapy related costs for the German health care system. Conclusions: Brachytherapy after successful balloon dilatation in PAOD can be recommended from a medical point of view for the reduction of the rate of restenosis at one year. However from a health economic view the answer is not yet clear. Based on the current data the use of brachytherapy after stenting in PAOD cannot be recommended neither from a medical nor from a health economic point of view. The informed consent of the patients is an important ethical aspect in the use of brachytherapy

Early benefit assessment (EBA) in Germany: analysing decisions 18 months after introducing the new AMNOG legislation

Since the introduction of the German health care reform in January 2011, an early benefit assessment (EBA) is required for all new medicines. Pharmaceutical manufacturers have to submit a benefit dossier for evaluation by the Institute for Quality and Efficiency in Health Care (IQWiG). A final decision is made by the Federal Joint Committee (G-BA). The aim of this investigation was to analyse the outcomes 18 months after introduction of the new legislation and to identify critical areas requiring further discussion and development. All EBAs commenced prior to June 2012 were included. The G-BA website was used to obtain manufacturers' benefit dossiers, IQWiG assessments, and G-BA decisions. Four areas of interest were analysed: levels of additional benefit, appropriate comparative therapy (ACT), patient-relevant endpoints, and adverse events. Twenty-seven EBAs were analysed. IQWiG stated a benefit in 50 % of EBAs, whereas G-BA stated a benefit in 63 %, but only in 50 % of identified subgroups and 40 % of patients involved. In 12 EBAs, the ACT suggested by G-BA differed from the comparator used in phase III trials. The G-BA reported no benefits on health-related quality of life. Discrepancies arose in morbidity outcomes such as 'progression-free survival' and 'sustained virological response'. Categorisation and balancing of adverse events was conducted within various assessments. Considerable variance was observed in the levels of additional benefit reported by pharmaceutical manufacturers, IQWiG and G-BA. The areas of disagreement included ACT selection, definition of subgroups and patient-relevant endpoints, and classification and balancing of adverse events.Roche Pharma A

Relevance of Variations in the Opposing Dentition for the Functionality of Fixed and Removable Partial Dentures: A Systematic Review

The aim of this systematic review was to evaluate the functionality of fixed and removable partial dentures as test interventions in relation to variations in the opposing dentition and their prosthetic restoration. The abstracts identified in the respective databases were screened independently by two investigators. RCTs and uncontrolled studies were considered, provided the patients were included consecutively and the confounding variables were adequately monitored. Seventeen papers were included. The study and publication quality was assessed using a “biometric quality” tool showing an overall poor quality. The reported outcomes, such as survival rates, were in each case obtained from a single study. Two possible trends could be deduced for the endpoint longevity: (a) the first trend in favor of removable partial dentures, compared to fixed partial dentures, with a fully edentulous opposing arch fitted with a removable prosthesis; (b) the second trend in favor of implant-supported partial dentures, compared to conventionally fixed partial dentures, with natural opposing dentition or with a removable partial denture in the opposing arch. No evidence could be generated as to whether, and if so how, variations in the opposing dentition have a bearing on the decision to fit a partially edentulous arch with a fixed or removable partial denture

Integrating patients' views into health technology assessment: Analytic hierarchy process (AHP) as a method to elicit patient preferences

Background: Patient involvement is widely acknowledged to be a valuable component in health technology assessment (HTA) and healthcare decision making. However, quantitative approaches to ascertain patients' preferences for treatment endpoints are not yet established. The objective of this study is to introduce the analytic hierarchy process (AHP) as a preference elicitation method in HTA. Based on a systematic literature review on the use of AHP in health care in 2009, the German Institute for Quality and Efficiency in Health Care (IQWiG) initiated an AHP study related to its HTA work in 2010. - \ud Methods: The AHP study included two AHP workshops, one with twelve patients and one with seven healthcare professionals. In these workshops, both patients and professionals rated their preferences with respect to the importance of different endpoints of antidepressant treatment by a pairwise comparison of individual endpoints. These comparisons were performed and evaluated by the AHP method and relative weights were generated for each endpoint. - \ud Results: The AHP study indicates that AHP is a well-structured technique whose cognitive demands were well handled by patients and professionals. The two groups rated some of the included endpoints of antidepressant treatment differently. For both groups, however, the same six of the eleven endpoints analyzed accounted for more than 80 percent of the total weight. - \ud Conclusions: AHP can be used in HTA to give a quantitative dimension to patients' preferences for treatment endpoints. Preference elicitation could provide important information at various stages of HTA and challenge opinions on the importance of endpoints

How Far is Germany From Value-Based Pricing 10 Years After the Introduction of AMNOG?

This is the first study that highlighted the amount of missed information related on bone health in orthogeriatric patients suffering fragility fractures of the pelvis and also evaluated its prevalence and differing etiology in the assessed patients, regarding osteoporosis and/or osteomalacia, based on laboratory and instrumental measurements. This evaluation should become a standardized procedure in the treatment of orthogeriatric patients presenting with a FFP.!##!Introduction!#!Fragility fractures of the pelvis (FFP) are common in orthogeriatric patients. Secondary fracture prevention regarding evaluation and treatment of an underlying osteoporosis or osteomalacia is still often neglected. The purpose of this study was to evaluate the amount of missed information related on bone health in older adult FFP patients, the prevalence of vitamin D deficiency in assessed patients, and if fracture type-dependent distribution patterns could be observed.!##!Methods!#!A retrospective analysis of prospectively collected data of an institutional register was performed. Patients aged 80 years and older (n = 456) admitted with a FFP from 01/2003 until 12/2019 to a level I trauma center were included.!##!Results!#!In 456 patients, FFP type II were leading (66.7%). Diagnostics were conducted in 37.1% of the patients regarding measurement of vitamin D levels and 21.7% regarding DXA measurements; vitamin D deficiency was observed in 62.7%, indicators for an underlying osteomalacia in 45.8%, and an osteoporosis in 46.5% of the assessed patients.!##!Conclusion!#!Although FFP are common and will increase, there is still a lack of secondary fracture prevention, starting with information related on bone health. In the assessed patients, a high prevalence of vitamin D deficiency was present, but no significant correlation between vitamin D level and type of fracture was observed. Ongoing education for varying etiology and specific treatment of these fractures is necessary, as surgical treatment was unified, but drug therapy remains different