metcardio.org
 Meta-analysis and Evidence-based Medicine Training in Cardiology
The metcardio.org website is dedicated to meta-analysis and evidence-based medicine training in cardiology. It is sponsored by the Meta-analysis and Evidence-based medicine Training in Cardiology (METCARDIO) Group, currently headquartered in Turin, Italy, and formerly known as the Center for Overview, Meta-analysis, and Evidence-based Medicine Training (COMET). The focus of the metcardio.org website is on clinical research methods and evidence-based cardiovascular medicine with a specific interest in interventional cardiology and peripheral cardiovascular interventions. Nonetheless, there is plenty of training and research opportunities for other evidence-based endeavors, eg in anesthesiology, critical care medicine, and psychiatry.


Title: Antithrombotic Therapy in Atrial Fibrillation. A Novel Approach to Indirectly Compare Benefit: Risk Across Treatments.
First author: Ariel Dogliotti, MD, Unidad de Epidemiología Clínica y Estadística, Grupo Oroño, Bvrd. Oroño 450, 2000 Rosario (Santa Fe), Argentina. Phone: +54 3414203040. Fax: +54 3414203040. Email: arieldogliotti@hotmail.com.
Corresponding author: Robert P. Giugliano, MD, SM, Brigham and Women´s Hospital, Harvard Medical School, TIMI Study Group, 350 Longwood Avenue, 1st Floor Offices, Boston, MA 02115, USA. Phone: +1 6172780145. Fax: +1 6177347320. Email: rgiugliano@partners.org.
Review type: Network meta-analysis.
Search strategy: Randomised controlled trials in patients with AF of antithrombotic therapies will be identified from MEDLINE, Embase, and Cochrane Central Register of Controlled Trials through December 2013 of aspirin (ASA), clopidogrel and anticoagulants.
Other details: We will perform a network meta-analysis and a stochastic multi-criteria acceptability analysis, which allows to compute the typical value judgment that support a decision, to quantify decision uncertainly, and to compute a comprehensive benefit-risk profile. In the analysis, we will use prior established rankings of mortality, intracranial hemorrhage, ischemic stroke, myocardial infarction, major extracranial hemorrhage and systemic embolism based on utility functions, and mortality followed by, major extracranial hemorrhage, ischemic stroke, myocardial infarction, intracranial hemorrhage and systemic embolism based on costs to order the importance of these clinical events. In sensitivity analyses, we will explore: ranking all the bleeding events higher than thromboembolic events and vice versa, since these two scenarios represent the extremes. Inclusion criteria for retrieved studies will be: a) randomized controlled trials of VKA (adjusted dose), ASA, clopidogrel, and NOAC in patients with nonvalvular atrial fibrillation; b) intention-to-treat analysis; c) minimum 1 year follow-up Data abstraction and quality assessment Two independent reviewers will perform data extraction. We will use consensus to resolve discrepancies. The endpoints of interest will be: mortality from any cause, ischemic stroke, myocardial infarction and systemic embolism (efficacy outcomes); intracranial hemorrhage and major extracranial hemorrhage (safety outcomes). We will use data from the intention-to-treat populations. Network meta-analysis will be carried out in the Bayesian framework using Markov Chain Monte Carlo simulation in the GeMTC R package. The analysis pooled relative effects on the odds ratio scale using the binomial likelihood and logit link function. GeMTC automatically specified vague prior distributions for the trial baseline effects, the relative effects, and the random effects standard deviation. First, a random-effects model network meta-analysis will be performed. The statistical analysis is based on binomial likelihoods with a logit link function. GeMTC automatically specified vague prior distributions for the trial baseline effects, the relative effects (normal with mean 0 and standard deviation 37.5), and the random effects standard deviation (uniform in the interval 0 to 2.5). We will use a technique known as "node-splitting" to evaluate for inconsistency in the findings of the network meta-analysis coming from direct vs. indirect evidence. Node-splitting assesses whether direct and indirect evidence on a specific node (the split node) are in agreement. Second, we will use a Stochastic Multi-criteria Acceptability Analysis-2 (SMAA-2) as a new and more elaborate approach to drug benefit-risk analysis to overcome the limitations of the net clinical benefit approach. SMAA was carried out based on the estimated incidence distributions of each of the events of interest (criteria). The incidence distributions were derived from relative effect estimates obtained from the network meta-analyses, combined with baseline incidence estimates for Warfarin treatment. We will perform two main analyses. The first used preference information based on utility functions (utility function is a generic multiattribute preference-based measure of health status and health-related quality of life that is widely used as an outcome measure in clinical studies, in population health surveys, in the estimation of quality-adjusted life years, and in economic evaluations). The second ordered event based on medical costs and using utility functions, the elicitation process resulted in the following ranking: mortality from any cause > intracranial hemorrhage > ischemic stroke > myocardial infarction > major extracranial hemorrhage > systemic embolism. Based on medical costs: mortality will be followed by, major extracranial hemorrhage, ischemic stroke, myocardial infarction, intracranial hemorrhage and systemic embolism. After that ranking, we will perform 2 sensitivity analyses: 1) ranking all the bleeding events higher than thromboembolic events and 2) ranking all the thromboembolic events higher than bleeding events, since these two scenarios represent the extremes. We also ranked the various antithrombotic treatments in terms of their likelihood of leading to the best results for each outcome (rank acceptability index). In this approach, the share of all possible values of the weight vector W and the joint random vector X for which alternative i is ranked at place r. is calculated. The value can be interpreted as the probability that alternative i is ranked at place r, where 0 indicates that the alternative will never obtain rank r and 1 indicates that alternative i will always obtain rank r. The rank acceptability index is computed numerically as a multidimensional integral over the criteria distributions and the favorable rank weights. The preferred (best) alternatives are those with the highest probabilities for the best ranks. The confidence factor (CF) is the probability for an alternative to obtain the first rank when the central weight vector is chosen. The confidence factor is computed as a multidimensional integral over the criteria distributions.

Title: Meta-analysis of Non-randomized Comparative Studies of Use of Bare-Metal vs. Drug-Eluting Stents for Extracranial Vertebral Artery Disease.
First author: Nicolas Langwieser (Principal Investigator and Corresponding Author), I. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Ismaninger Straße 22, 81675 München, Germany. E-mail: NicolasLangwieser@web.de.
Review type: Meta-analysis of observational, retrospective, single-center studies.
Search strategy: We performed a search in MEDLINE/PubMed using the terms “extracranial”, “vertebral”, “stenosis”, “stenting”, “bare-metal stents” and “drug-eluting stents”. In order to reduce interperformer variability, only those studies were included where both BMS and DES were used in the same setting and restenosis was evaluable during follow-up. Follow-up was considered evaluable when at least the clinical course or one reliable imaging method, e.g. duplex sonography, computed tomography angiography (CTA), magnetic resonance angiography (MRA) or catheter-based angiography, respectively, or a combination of these were available for both BMS and DES.

Title: Association between pneumococcal vaccination and cardiovascular outcomes: a systematic review and meta-analysis of cohort studies.
Principal investigator/corresponding author: Charalambos Vlachopoulos, MD, Peripheral Vessels Unit, 1st Department of Cardiology, Athens Medical School, Hippokration Hospital, Profiti Elia 24, Athens 14575, Greece. Tel: + 30 6972 272727. Fax: +30 2132088676. E-mail: cvlachop@otenet.gr.
Types of included studies: Observational cohort studies evaluating relationships of pneumococcal vaccination in adults with the risk of future cardiovascular events.
Detailed search strategy for MEDLINE/PubMed: Studies evaluating relationships of pneumococcal vaccination in adults with the risk of future clinical events were drawn from a systematic review of the English literature in the Medline, Cochrane and Embase databases until March 2014. The search terms were “pneumococcal” “pneumococcal vaccine”, “pneumococcal vaccination” or “pneumococcal immunization” and “prediction”, “cardiovascular disease”, “cardiac”, “heart”, “coronary”, “angina”, “ischemia”, “risk”, “death”, “mortality”, “outcome”, “myocardial infarction”, “stroke”, “transient ischemic attacks”, “intracranial hemorrhage” or “events”. The search was not restricted to any language.
Other details: Studies were deemed eligible if they: 1) were full-length publications in peer-reviewed journals or abstracts in major conventions; 2) included adult patients that received the 23-polyvalent pneumococcal vaccine and were compared to unvaccinated patients; 3) reported a combined cardiovascular outcome or cardiovascular mortality or myocardial infarction or cerebrovascular event 4) the follow-up period was at least 1 month and did not include exclusively in-hospital cardiovascular events, 5) were either retrospective or prospective cohort studies. Case-control studies, studies on all-cause mortality without specific cardiovascular endpoints, studies that compared co-administration of influenza and pneumococcal vaccine with no vaccination, studies on children, studies in which pneumococcal vaccination was used as a booster after conjugate pneumococcal vaccination, animal or laboratory studies and studies that reported only immunologic responses were excluded from our meta-analysis. Otherwise, no restriction criteria were imposed with regard to the type of the population studied (general population or populations with risk factors or disease) or the size of the population. The literature search, selection of studies, quality assessment and extraction of data were done independently by 2 reviewers.