Major ischaemic and bleeding risks following current drug-eluting stent implantation: Are there differences across current drug-eluting stent types in real life?

BACKGROUND: Current drug-eluting stents (c-DESs) reduce the occurrence of ischaemic events, but expose recipients to stent thrombosis and bleeding secondary to preventive antiplatelet therapy. To date, comparative data on the relative effectiveness and safety of the various c-DESs in real life are limited. AIM: To compare ischaemic and bleeding risks across the major c-DESs used in France. METHODS: French national health insurance reimbursement and hospitalization databases were used. Patients implanted with a c-DES in 2014 were followed for 1 year. The risks of ischaemic events (revascularization, myocardial infarction and/or stroke), major bleeding events and death were compared across six c-DESs (XIENCE®, PROMUS®, RESOLUTE®, BIOMATRIX®, NOBORI® and ORSIRO®), using multilevel Cox models adjusted for baseline individual and hospital characteristics. RESULTS: A total of 52,891 subjects were included: 34.4% with XIENCE®; 27.6% with PROMUS®; 24.0% with RESOLUTE®; 8.0% with BIOMATRIX®; 5.0% with NOBORI®; and 1.0% with ORSIRO®. Among them, 9378 had at least one event (ischaemic, 6064; major bleeding, 1968; death, 2411), resulting in an overall incidence rate of 19 per 100 person-years. In the multivariable analysis, the risk of ischaemic events, major bleeding events or death did not differ between the c-DESs overall (adjusted hazard ratios between 0.85 [95% confidence interval 0.68-1.07] and 1.04 [95% confidence interval 0.98-1.10] compared with XIENCE® used as the reference) and when each outcome was considered separately. CONCLUSIONS: In real life, major ischaemic and bleeding risks do not differ across the various c-DESs over the first year following implantation. Future studies are needed to assess comparative c-DES effectiveness and safety longer term.

Use of Mechanical Insufflation-Exsufflation Devices for Airway Clearance in Subjects With Neuromuscular Disease.

The aim of this systematic review is to examine the benefit/risk ratio of the use of mechanical insufflation-exsufflation (MI-E) devices for airway clearance in patients with neuromuscular diseases. A search was conducted for relevant studies in MEDLINE, the Cochrane Library, and the Health Technology Assessment Database using the main key words: cough, airway clearance, in-exsufflation. The search limits were studies published in English and French between 1970 and 2014 (literature watch until December 2015). The methodological quality of the studies was assessed using (1) the Cochrane Collaboration's risk of bias tool for randomized controlled trials and (2) the Institute of Health Economics' 20-item checklist for comparative and observational studies. Data were extracted into an evidence table according to (1) study design, (2) population characteristics (including age and type of diseases) and intervention (MI-E associated or not with other interventions), (3) outcome measures, and (4) key findings. Twelve studies met the inclusion criteria (4 randomized controlled trials, 3 comparative studies, and 5 observational studies). The quality of the selected studies was poor. None of the studies reported survival outcome. All studies evaluated change of pulmonary function parameters, such as peak expiratory flow. This review underlines the lack of robust data on mechanical medical devices used for airway clearance. The current scientific evidence does not support the use of MI-E for cough augmentation in patients with neuromuscular diseases, but health-care professionals are faced with the reality of medical practice and the absence of alternatives. Most European and American guidelines recommend the use of MI-E despite low-level evidence. However, even if performing comparative trials in a specific population is difficult, the medical device industry should provide reliable data to assist health-care professionals, providers, and payers in the decision-making process. This is the only way to ensure the best treatment for patients.

Methodological choices for the clinical development of medical devices.

Clinical evidence available for the assessment of medical devices (MDs) is frequently insufficient. New MDs should be subjected to high quality clinical studies to demonstrate their benefit to patients. The randomized controlled trial (RCT) is the study design reaching the highest level of evidence in order to demonstrate the efficacy of a new MD. However, the clinical context of some MDs makes it difficult to carry out a conventional RCT. The objectives of this review are to present problems related to conducting conventional RCTs and to identify other experimental designs, their limitations, and their applications. A systematic literature search was conducted for the period January 2000 to July 2012 by searching medical bibliographic databases. Problems related to conducting conventional RCTs of MDs were identified: timing the assessment, eligible population and recruitment, acceptability, blinding, choice of comparator group, and learning curve. Other types of experimental designs have been described. Zelen's design trials and randomized consent design trials facilitate the recruitment of patients, but can cause ethical problems to arise. Expertise-based RCTs involve randomization to a team that specializes in a given intervention. Sometimes, the feasibility of an expertise-based randomized trial may be greater than that of a conventional trial. Cross-over trials reduce the number of patients, but are not applicable when a learning curve is required. Sequential trials have the advantage of allowing a trial to be stopped early depending on the results of first inclusions, but they require an independent committee. Bayesian methods combine existing information with information from the ongoing trial. These methods are particularly useful in situations where the number of subjects is small. The disadvantage is the risk of including erroneous prior information. Other types of experimental designs exist when conventional trials cannot always be applied to the clinical development of MDs.

[Which indications and access routes for transcatheter aortic valve implantation? Health technology assessment from HAS]. / Quelles indications et quelles voies d'abord pour l'implantation des valves aortiques percutanées ? Évaluation technologique menée par la Haute Autorité de santé (HAS).

The transcatheter aortic valve implantation should be restricted to patients with severe symptomatic aortic stenosis with a contraindication for a surgical replacement (taking into account surgical risk scores, comorbidities, anatomical conditions, life expectancy and frailty). Patient eligibility should be performed by a heart team with the involvement of a cardiac surgeon, an interventional cardiologist, a clinical cardiologist and an anaesthetist/resuscitation specialist. The advice of a geriatrician is strongly recommended. The long-term efficacy remains unknown. The French National Authority for Health (Haute Autorité de santé [HAS]) reminds that contraindications in the CE mark should be strictly respected (i.e.instructions for use). Extension of current indications should be conditional to the presentation of clinical evidence. Thus, implantation in patients at lower surgical risk or the use of direct transaortic route are not eligible for reimbursement given the current state of knowledge.

Drug-eluting stents in patients at high risk of restenosis: assessment for France.

BACKGROUND: In unselected patients, the incidence of restenosis is lower after placement of drug-eluting stents (DES) than bare-metal stents (BMS) without difference in safety at a time horizon of 4 years. However, DES appears less effective in "off label" patients. OBJECTIVES: The aim of the study was to assess available evidence of DES efficacy and safety by patient category to establish when DES placement may be recommended for reimbursement by the French national health insurance. METHODS: Based on a systematic review by patient category (January 2002 to August 2009), two health technology assessment (HTA) reports and thirty-eight clinical studies not covered by the HTA reports (eleven meta-analysis including ours, eleven randomized trials and sixteen cohort studies) were selected. After assessment of the methodological quality, the studies mostly comparing DES with BMS were reviewed by a panel of health professionals who defined a priori the most relevant end points of safety and efficacy. RESULTS: Seven to fourteen patients treated with DES were needed to avoid one target lesion revascularization (TLR) in patients with lesions >15 mm long, vessel diameter <3 mm, or diabetes, and with some complex lesions (total coronary occlusion, BMS in-stent restenosis multivessel disease, unprotected left main stenosis). DES appeared as safe as other alternatives over a follow-up of up to 4 years when dual antiplatelet therapy was continued for at least 1 year, but statistical power remains limited to conclude for some clinical features. CONCLUSIONS: For reimbursement, DES use should be limited to certain categories of patients. Treatment of particular cases requires a multidisciplinary approach.