Exercise training for chronic heart failure (ExTraMATCH II): Protocol for an individual participant data meta-analysis Rod S. Taylor a, ⁎ ,1 , Massimo F. Piepoli b , Neil Smart c , Andrew J.S. Coats d , Stephen Ellis e , Hayes Dalal f , Christopher M. O'Connor g , Fiona C. Warren h , David Whellan e , Oriana Ciani a , on behalf of ExTraMATCH II Collaborators a Institute of Health Research, Exeter Medical School, University of Exeter, UK b Heart Failure Unit, Guglielmo da Saliceto Hospital, Piacenza, Italy c School of Science and Technology, University of New England, Armidale, NSW, Australia d Monash University, Australia and University of Warwick, UK e Duke Clinical Research Institute, NC, USA f Research & Development, Knowledge Spa, Royal Cornwall Hospitals Trust, Truro & Primary Care Research Group, Exeter Medical School, UK g Division of Cardiology and Clinical Pharmacology, Duke Heart Center, NC, USA h Primary Care Research Group, Exeter Medical School, Exeter, UK abstract article info Article history: Received 10 February 2014 Received in revised form 15 April 2014 Accepted 18 April 2014 Available online 26 April 2014 Keywords: Heart failure Meta-analysis Individual participant data Exercise-training Cardiac rehabilitation Background: Patients with chronic heart failure (HF) experience a marked reduction in their exercise capacity, health-related quality of life, and life expectancy. Despite substantive evidence supporting exercise training in HF, uncertainties remain in the interpretation and understanding of this evidence base. Clinicians and healthcare providers seek definitive estimates of impact on mortality, hospitalisation and health-related quality of life, and which HF patient subgroups are likely to most benefit. The original Exercise Training Meta-Analysis for Chronic Heart Failure (ExTraMATCH) individual participant data (IPD) meta-analysis conducted in 2004 will be updated by the current collaboration (ExTraMATCH II), to investigate the effects of exercise training in HF. Methods: Randomised controlled trials have been identified from the updated 2014 Cochrane systematic review and the original ExTraMATCH IPD meta-analysis with exercise training of 3 weeks' duration or more compared with a non-exercise control and a minimum follow-up of 6 months. Particular outcomes of interest are mortality, hospitalisation and health-related quality of life plus key baseline patient demographic and clinical data. Original IPD will be requested from the authors of all eligible trials; we will check original data and compile a master dataset. IPD meta-analyses will be conducted using a one-step approach where the IPD from all studies are modelled simultaneously whilst accounting for the clustering of participants with studies. Discussion: The information from ExTraMATCH II will help inform future national and international clinical and policy decision-making on the use of exercise-based interventions in HF and improve the quality, design and reporting of future trials in this field. © 2014 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Patients with chronic heart failure (HF) experience a marked reduc- tion in exercise capacity, which has detrimental effects on their activities of daily living, health-related quality of life, hospital admission rate and survival [1]. Exercise training is known to reduce the debilitating symptoms of chronic HF, such as breathlessness and fatigue, through effects on the cardiovascular and musculoskeletal systems [2,3]. Meta-analyses have shown that exercise interventions can improve short-term (up to 12 months' follow-up) exercise capacity of those with HF [4,5]. Exercise training is therefore increasingly recognised as an important adjunct in the management of HF and is recommended by the American College of Cardiology Foundation/American Heart Association Task Force, the European Society of Cardiology, and other national guidelines [6–9]. However, some key issues in the interpretation and understanding of the evidence base for exercise training in HF remain. First is uncertainty of the impact of exercise training in HF on the outcomes of death and hospital admission. In 2004, the Exercise Training Meta-Analysis for Chronic Heart Failure (ExTraMATCH) Collaborative Group published an individual participant data (IPD) meta-analysis [10] that showed a reduction in both all-cause mortality (hazard ratio (HR): International Journal of Cardiology 174 (2014) 683–687 ⁎ Corresponding author at: Exeter Medical School, University of Exeter, Veysey Building, Salmon Pool Lane, Exeter, EX2 4SG, UK. Tel.: +44 7968 152537; fax: +44 1932 421009. E-mail address: r.taylor@exeter.ac.uk (R.S. Taylor). 1 This author takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. http://dx.doi.org/10.1016/j.ijcard.2014.04.203 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved. 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