{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T10:51:33Z","timestamp":1782903093037,"version":"3.54.5"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Health Serv."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Atrial fibrillation (AF) is the most common cardiac arrhythmia. The associated risk of stroke can be effectively reduced by oral anticoagulation; however, these increase bleeding risk or can even be contraindicated. Clinical studies indicate that percutaneous catheter-based left atrial appendage closure (LAAC) may represent an effective alternative for stroke prevention in this high-risk patient group. While the clinical and economic benefits of LAAC have been compared with standard drug therapy indirectly, direct comparisons are lacking, especially for patients with AF at high risk of stroke and bleeding. EvaClosure, a substudy of the CLOSURE-AF-DZHK16 trial, was designed to describe current therapy paths of patients with AF and high risk of stroke and bleeding, while quantifying resource utilization and healthcare costs. Moreover, this study aims to evaluate the health economic impact of LAAC in patients with high risk of stroke and bleeding, compared with the best physician-directed medical therapy (including direct oral anticoagulants when eligible).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Data gathered in CLOSURE-AF address the effect of different treatment options on health-related quality of life; analyses of resource utilization and healthcare costs are based on claims data from a German statutory health insurance (SHI) provider. Economic information derived from SHI data is complemented by a validated resource use measurement instrument capturing non-medical and indirect costs. The cost\u2013utility analysis uses a Markov model, for which parameters are quantified from statistically matched SHI claims and CLOSURE-AF clinical study data, supplemented by data from the literature.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>The combination of these databases allows a comprehensive, valid, and policy-relevant assessment of costs and benefits related to LAAC. Moreover, the advantages of the different databases are used for health economic evaluation. The results of this study are expected to generate robust evidence to inform health economic evaluations and provide valuable insights for SHI providers and policymakers on the societal and economic impact of LAAC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>ClinicalTrials.gov<\/jats:ext-link>\n                      , Identifier NCT03463317. The clinical study CLOSURE-AF-DZHK16, including the substudy EvaClosure, was registered at ClinicalTrials.gov PRS (Identifier: NCT03463317, Posted: March 13, 2018, Update: July 30, 2021).\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/frhs.2026.1771683","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T10:40:48Z","timestamp":1782902448000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Health economic evaluation of left atrial appendage closure in patients with atrial fibrillation and at high risk for stroke and bleeding: a study protocol"],"prefix":"10.3389","volume":"6","author":[{"given":"Franziska","family":"Claus","sequence":"first","affiliation":[{"name":"Scientific Institute for Health Economics and Health System Research","place":["Leipzig, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Scientific Institute for Health Economics and Health System Research","place":["Leipzig, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Fa\u00df","sequence":"additional","affiliation":[{"name":"Scientific Institute for Health Economics and Health System Research","place":["Leipzig, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Diesing","sequence":"additional","affiliation":[{"name":"Scientific Institute for Health Economics and Health System Research","place":["Leipzig, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Skurk","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charit\u00e9, Charit\u00e9-University Medicine Berlin, Campus Benjamin Franklin","place":["Berlin, Germany"]},{"name":"German Center for Cardiovascular Research (DZHK), partner site Berlin","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Seppelt","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charit\u00e9, Charit\u00e9-University Medicine Berlin, Campus Benjamin Franklin","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denitsa","family":"Meteva","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charit\u00e9, Charit\u00e9-University Medicine Berlin, Campus Benjamin Franklin","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andi","family":"Rroku","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charit\u00e9, Charit\u00e9-University Medicine Berlin, Campus Benjamin Franklin","place":["Berlin, Germany"]},{"name":"German Center for Cardiovascular Research (DZHK), partner site Berlin","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingo","family":"Eitel","sequence":"additional","affiliation":[{"name":"German Center for Cardiovascular Research (DZHK), partner site Hamburg\/Kiel\/L\u00fcbeck","place":["L\u00fcbeck, Germany"]},{"name":"University Heart Center L\u00fcbeck, Medical Clinic II (Cardiology\/Angiology\/Intensive Care Medicine)","place":["L\u00fcbeck, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leif-Hendrik","family":"Boldt","sequence":"additional","affiliation":[{"name":"German Center for Cardiovascular Research (DZHK), partner site Berlin","place":["Berlin, Germany"]},{"name":"Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charit\u00e9, Charit\u00e9-University Medicine Berlin, Campus Virchow","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf","family":"Landmesser","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charit\u00e9, Charit\u00e9-University Medicine Berlin, Campus Benjamin Franklin","place":["Berlin, Germany"]},{"name":"German Center for Cardiovascular Research (DZHK), partner site Berlin","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eberhard","family":"Wille","sequence":"additional","affiliation":[{"name":"Department of Economics, University of Mannheim","place":["Mannheim, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ines","family":"Weinhold","sequence":"additional","affiliation":[{"name":"Scientific Institute for Health Economics and Health System Research","place":["Leipzig, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e56","DOI":"10.1161\/CIR.0000000000000659","article-title":"Heart disease and stroke statistics-2019 update: a report from the American Heart Association","volume":"139","author":"Benjamin","year":"2019","journal-title":"Circulation"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1468","DOI":"10.1093\/europace\/euz141","article-title":"Prevalence of atrial fibrillation in the Italian elderly population and projections from 2020 to 2060 for Italy and the European union: the FAI project","volume":"21","author":"Di Carlo","year":"2019","journal-title":"Europace"},{"key":"B3","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1177\/1747493019897870","article-title":"Global epidemiology of atrial fibrillation: an increasing epidemic and public health challenge","volume":"16","author":"Lippi","year":"2021","journal-title":"Int J Stroke"},{"key":"B4","volume-title":"H\u00e4ufigkeit und Kosten von Isch\u00e4mischen Schlaganf\u00e4llen und Vorhofflimmern in Deutschland (GKV) Unter Ber\u00fccksichtigung von Versorgungsaspekten","author":"H\u00f6er","year":"2023"},{"key":"B5","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1136\/heartjnl-2020-318882","article-title":"Refined atrial fibrillation screening and cost-effectiveness in the German population","volume":"108","author":"Schnabel","year":"2022","journal-title":"Heart"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1588","DOI":"10.1161\/CIRCULATIONAHA.117.028981","article-title":"Sex differences and similarities in atrial fibrillation epidemiology, risk factors, and mortality in community cohorts: results from the BiomarCaRE consortium (biomarker for cardiovascular risk assessment in Europe)","volume":"136","author":"Magnussen","year":"2017","journal-title":"Circulation"},{"key":"B7","doi-asserted-by":"publisher","first-page":"k1453","DOI":"10.1136\/bmj.k1453","article-title":"Lifetime risk of atrial fibrillation according to optimal, borderline, or elevated levels of risk factors: cohort study based on longitudinal data from the Framingham heart study","volume":"361","author":"Staerk","year":"2018","journal-title":"Br Med J"},{"key":"B8","doi-asserted-by":"publisher","first-page":"2369","DOI":"10.1093\/eurheartj\/ehq278","article-title":"Guidelines for the management of atrial fibrillation: the task force for the management of atrial fibrillation of the European Society of Cardiology (ESC)","volume":"31","author":"Camm","year":"2010","journal-title":"Eur Heart J"},{"key":"B9","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1055\/s-0043-121630","article-title":"Sekund\u00e4rpr\u00e4vention des isch\u00e4mischen schlaganfalls bei vorhofflimmern oder karotisstenose","volume":"6","author":"H\u00e4usler","year":"2017","journal-title":"Aktuelle Kardiologie"},{"key":"B10","doi-asserted-by":"publisher","first-page":"2882","DOI":"10.1093\/eurheartj\/ehw233","article-title":"Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF","volume":"37","author":"Bassand","year":"2016","journal-title":"Eur Heart J"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.1093\/europace\/eur194","article-title":"The cost of illness of atrial fibrillation: a systematic review of the recent literature","volume":"13","author":"Wolowacz","year":"2011","journal-title":"Europace"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.2217\/cer-2019-0089","article-title":"Systematic review of societal costs associated with stroke, bleeding and monitoring in atrial fibrillation","volume":"8","author":"Martin","year":"2019","journal-title":"J Comp Eff Res"},{"key":"B13","doi-asserted-by":"publisher","first-page":"317","DOI":"10.2165\/11319880-000000000-00000","article-title":"Cost of illness and drivers of cost in atrial fibrillation in Sweden and Germany","volume":"8","author":"J\u00f6nsson","year":"2010","journal-title":"Appl Health Econ Health Policy"},{"key":"B14","doi-asserted-by":"publisher","first-page":"S101","DOI":"10.1016\/j.jval.2018.09.601","article-title":"Estimated economic burden of atrial fibrillation in Germany, Italy, and the UK","volume":"21","author":"Velleca","year":"2018","journal-title":"Value Health"},{"key":"B15","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1093\/ehjqcco\/qcaa093","article-title":"Atrial fibrillation in the United Kingdom: predicting costs of an emerging epidemic recognising and forecasting the cost drivers of atrial fibrillation-related costs","volume":"8","author":"Burdett","year":"2020","journal-title":"Eur Heart J Qual Care Clin Outcomes"},{"key":"B16","doi-asserted-by":"publisher","first-page":"2093","DOI":"10.1056\/NEJMoa1310907","article-title":"Edoxaban versus warfarin in patients with atrial fibrillation","volume":"369","author":"Giugliano","year":"2013","journal-title":"N Engl J Med"},{"key":"B17","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1056\/NEJMoa1107039","article-title":"Apixaban versus warfarin in patients with atrial fibrillation","volume":"365","author":"Granger","year":"2011","journal-title":"N Engl J Med"},{"key":"B18","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1016\/j.brat.2011.06.012","article-title":"Improving access to psychological treatments: lessons from developing countries","volume":"49","author":"Patel","year":"2011","journal-title":"Behav Res Ther"},{"key":"B19","doi-asserted-by":"publisher","first-page":"955","DOI":"10.1016\/S0140-6736(13)62343-0","article-title":"Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials","volume":"383","author":"Ruff","year":"2014","journal-title":"Lancet"},{"key":"B20","doi-asserted-by":"publisher","first-page":"e002031","DOI":"10.1161\/JAHA.115.002031","article-title":"Increased heart rate is associated with higher mortality in patients with atrial fibrillation (AF): results from the outcomes registry for better informed treatment of AF (ORBIT-AF)","volume":"4","author":"Steinberg","year":"2015","journal-title":"J Am Heart Assoc"},{"key":"B21","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1093\/eurheartj\/ehaa612","article-title":"2020 ESC guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European association for cardio-thoracic surgery (EACTS): the task force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) developed with the special contribution of the European heart rhythm association (EHRA) of the ESC","volume":"42","author":"Hindricks","year":"2021","journal-title":"Eur Heart J"},{"key":"B22","first-page":"1","article-title":"Left atrial appendage closure device with delivery system: a health technology assessment","volume":"17","year":"2017","journal-title":"Ont Health Technol Assess Ser"},{"key":"B23","doi-asserted-by":"publisher","first-page":"107273","DOI":"10.1016\/j.ahj.2025.09.005","article-title":"Catheter-based left atrial appendage CLOSURE in patients with atrial fibrillation at high risk of stroke and bleeding as compared to best medical therapy: rationale and design of the prospective randomized CLOSURE-AF trial","volume":"292","author":"Landmesser","year":"2025","journal-title":"Am Heart J"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1270","DOI":"10.1056\/NEJMoa2513310","article-title":"Left atrial appendage closure or medical therapy in atrial fibrillation","volume":"394","author":"Landmesser","year":"2026","journal-title":"N Engl J Med"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1093\/europace\/euu038","article-title":"The budget impact of left atrial appendage closure compared with adjusted-dose warfarin and dabigatran etexilate for stroke prevention in atrial fibrillation","volume":"16","author":"Amorosi","year":"2014","journal-title":"Europace"},{"key":"B26","doi-asserted-by":"publisher","first-page":"e003407","DOI":"10.1161\/CIRCEP.115.003407","article-title":"Cost-effectiveness of percutaneous closure of the left atrial appendage in atrial fibrillation based on results from PROTECT AF versus PREVAIL","volume":"9","author":"Freeman","year":"2016","journal-title":"Circ Arrhythm Electrophysiol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1186\/s12872-016-0351-y","article-title":"Cost-effectiveness analysis of left atrial appendage occlusion compared with pharmacological strategies for stroke prevention in atrial fibrillation","volume":"16","author":"Lee","year":"2016","journal-title":"BMC Cardiovasc Disord"},{"key":"B28","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1177\/0272989X15593083","article-title":"A decision analysis of percutaneous left atrial appendage occlusion relative to novel and traditional oral anticoagulation for stroke prevention in patients with new-onset atrial fibrillation","volume":"36","author":"Micieli","year":"2016","journal-title":"Med Decis Making"},{"key":"B29","doi-asserted-by":"publisher","first-page":"2728","DOI":"10.1016\/j.jacc.2015.09.084","article-title":"Time to cost-effectiveness following stroke reduction strategies in AF: warfarin versus NOACs versus LAA closure","volume":"66","author":"Reddy","year":"2015","journal-title":"J Am Coll Cardiol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1093\/europace\/euv412","article-title":"Cost effectiveness of left atrial appendage closure with the watchman device for atrial fibrillation patients with absolute contraindications to warfarin","volume":"18","author":"Reddy","year":"2016","journal-title":"Europace"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1355.e9","DOI":"10.1016\/j.cjca.2016.02.056","article-title":"Cost-effectiveness of left atrial appendage closure for stroke prevention in atrial fibrillation patients with contraindications to anticoagulation","volume":"32","author":"Saw","year":"2016","journal-title":"Can J Cardiol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"2414","DOI":"10.1161\/CIRCULATIONAHA.112.000920","article-title":"Economic evaluation of percutaneous left atrial appendage occlusion, dabigatran, and warfarin for stroke prevention in patients with nonvalvular atrial fibrillation","volume":"127","author":"Singh","year":"2013","journal-title":"Circulation"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1727","DOI":"10.1007\/s11136-011-9903-x","article-title":"Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L)","volume":"20","author":"Herdman","year":"2011","journal-title":"Qual Life Res"},{"key":"B34","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1007\/s11136-020-02688-y","article-title":"Psychometric properties of the EQ-5D-5L: a systematic review of the literature","volume":"30","author":"Feng","year":"2021","journal-title":"Qual Life Res"},{"key":"B35","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1055\/s-0034-1372618","article-title":"FIMA\u2013Fragebogen zur erhebung von gesundheitsleistungen im alter: entwicklung und pilotstudie","volume":"77","author":"Seidl","year":"2015","journal-title":"Gesundheitswesen"},{"key":"B36","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1055\/a-1010-6315","article-title":"Validierung des FIMA-fragebogens zur inanspruchnahme von versorgungsleistungen anhand von routinedaten der krankenversicherung: welchen einfluss hat der erinnerungszeitraum?","volume":"83","author":"Seidl","year":"2021","journal-title":"Das Gesundheitswesen"},{"key":"B37","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1378\/chest.09-1584","article-title":"Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation","volume":"137","author":"Lip","year":"2010","journal-title":"Chest"},{"key":"B38","doi-asserted-by":"publisher","first-page":"1093","DOI":"10.1378\/chest.10-0134","article-title":"A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the euro heart survey","volume":"138","author":"Pisters","year":"2010","journal-title":"Chest"},{"key":"B39","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1093\/pan\/mpr025","article-title":"Entropy balancing for causal effects: a multivariate reweighting method to produce balanced samples in observational studies","volume":"20","author":"Hainmueller","year":"2012","journal-title":"Polit Anal"},{"key":"B40","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1017\/pan.2022.12","article-title":"Hierarchically regularized entropy balancing","volume":"31","author":"Xu","year":"2023","journal-title":"Polit Anal"},{"key":"B41","year":""},{"key":"B42","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1055\/s-0034-1374621","article-title":"Ermittlung standardisierter bewertungss\u00e4tze aus gesellschaftlicher perspektive f\u00fcr die gesundheits\u00f6konomische evaluation","volume":"77","author":"Bock","year":"2015","journal-title":"Gesundheitswesen"},{"key":"B43","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1055\/a-2169-1480","article-title":"Aktualisierung der standardisierten bewertungss\u00e4tze aus gesellschaftlicher perspektive f\u00fcr gesundheits\u00f6konomische evaluationen","volume":"86","author":"Muntendorf","year":"2024","journal-title":"Gesundheitswesen"},{"key":"B44","doi-asserted-by":"crossref","DOI":"10.1093\/oso\/9780198529446.001.0001","volume-title":"Methods for the Economic Evaluation of Health Care Programmes","author":"Drummond","year":"2005"},{"key":"B45","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1007\/s40273-018-0642-5","article-title":"A systematic review of studies comparing the measurement properties of the three-level and five-level versions of the EQ-5D","volume":"36","author":"Buchholz","year":"2018","journal-title":"PharmacoEconomics"},{"key":"B46","doi-asserted-by":"publisher","first-page":"e011577","DOI":"10.1161\/JAHA.118.011577","article-title":"Cost-effectiveness of left atrial appendage closure for stroke reduction in atrial fibrillation: analysis of pooled, 5-year, long-term data","volume":"8","author":"Reddy","year":"2019","journal-title":"J Am Heart Assoc"},{"key":"B47","volume-title":"Allgemeine Methoden: Version 7.0","year":"2023"},{"key":"B48","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1055\/s-2007-963505","article-title":"Deutsche empfehlungen zur gesundheits\u00f6konomischen evaluation\u2014dritte und aktualisierte fassung des hannoveraner konsens","volume":"12","author":"Graf von der Schulenburg","year":"2007","journal-title":"Gesundh \u00f6kon Qual Manag"},{"key":"B49","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1002\/hec.901","article-title":"Calculation of quality adjusted life years in the published literature: a review of methodology and transparency","volume":"13","author":"Richardson","year":"2004","journal-title":"Health Econ"},{"key":"B50","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1007\/s00059-021-05065-8","article-title":"Linksatrialer vorhofohrverschluss: aktuelle daten und zuk\u00fcnftige entwicklungen","volume":"46","author":"Skurk","year":"2021","journal-title":"Herz"},{"key":"B51","doi-asserted-by":"publisher","first-page":"1503","DOI":"10.1016\/j.jacc.2019.12.040","article-title":"The NCDR left atrial appendage occlusion registry","volume":"75","author":"Freeman","year":"2020","journal-title":"J Am Coll Cardiol"},{"key":"B52","doi-asserted-by":"publisher","first-page":"1294","DOI":"10.1161\/CIRCULATIONAHA.107.703579","article-title":"Beyond the randomized clinical trial: the role of effectiveness studies in evaluating cardiovascular therapies","volume":"118","author":"Nallamothu","year":"2008","journal-title":"Circulation"}],"container-title":["Frontiers in Health Services"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/frhs.2026.1771683\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T10:40:49Z","timestamp":1782902449000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/frhs.2026.1771683\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,1]]},"references-count":52,"alternative-id":["10.3389\/frhs.2026.1771683"],"URL":"https:\/\/doi.org\/10.3389\/frhs.2026.1771683","relation":{},"ISSN":["2813-0146"],"issn-type":[{"value":"2813-0146","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,1]]},"article-number":"1771683"}}