Title: Exercise-based rehabilitation for chronic heart failure (ExTraMATCH II): An individual participant data meta-analysis of randomised controlled trials
Funder: Department of Health and Social Care

Abstract: Design: Individual patient data meta-analysis based on data from randomised controlled trials. PROSPERO registration number: CRD42014007170. Strategy for reviewing literature: 2014 Cochrane review - databases searches up to January 2013: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In-Process, EMBASE, CINAHL, PsycINFO, Web of Science and trial registers. Target population: Adults with chronic heart failure. Inclusion/exclusion criteria: randomised trials in adult (>18 years) patients with a diagnosis of systolic or diastolic heart failure (based on objective assessment of left ventricular ejection fraction and on clinical findings) and reported follow-up for 6 months or more post-randomisation. Trials in which participants had previously received exercise-based rehabilitation were excluded. Health technology being assessed: Exercise-based rehabilitation, that should include at least an aerobic exercise training component performed by the lower limbs, lasting a minimum of 3 weeks, either alone or as part of a comprehensive cardiac rehabilitation programme defined as also including components of health education and psychological treatment. The comparator was a no exercise group receiving standard medical care or an attention placebo. We excluded interventions without an exercise training component or head to head comparisons of two or more exercise interventions/ Measurement of costs and outcomes: we sought individual patient data for the following outcomes from eligible trials: mortality (all-cause, death due to heart failure and sudden cardiac death): incidence and time-to-event; hospital admission/re-admission (all-cause, heart failure specific): incidence, duration and time-to-event; disease specific health-related quality of life assessed by the Minnesota Living With Heart Failure questionnaire and other validated quality of life outcomes: outcome at baseline (pre-randomisation) and at 6, 12, 24 and >24 months post-randomisation; and exercise capacity (irrespective of assessment method): outcome at baseline and at 6, 12, 24 and >24 months post-randomisation. Sample size: We restricted inclusion to trials with sample size of more than 50, to ensure that the logistical effort in obtaining, cleaning and organising the data is commensurate with the contribution of the data set to the analysis. Difference between current and planned care: included trials have been undertaken across a number countries (UK, Denmark, US, Canada, Italy, Australia, Germany, Poland). Project timetable: data verification, cleaning & merging: Nov 2016 to Apr 2017; data analysis: Jan 17 to Sept 17; final write up Sept 17 to Nov 17. Project progress: we have obtained data on 20 out of 23 trials that meet above criteria that includes outcome and subgroup data on 4,046 patients. Expertise: the project brings together a multidisciplinary team that includes expertise in cardiology (MP, NS) and cardiac rehabilitation (RT, MP, NS), clinical trial design (RT, OC), statistical methods, including IPD meta-analysis (FW, OC), and data programming and data security (TE). The project will be led by RT, an NIHR Senior Investigator. Service input to the project will be provided by Kevin Paul who has agreed to sit on the Project Advisory Group and provide active linkage to our IPP group of patients with lived experience of heart failure and their carers.

Lay abstract: Aim: The Exercise Training Meta-Analysis for Chronic Heart Failure - ExTraMATCH II - project aims to determine which heart failure patient subgroups benefit most from exercise-based rehabilitation project using individual patient data meta-analysis. As a reanalysis of existing datasets, this proposed individual patient data meta-analysis falls in the remit of Efficient Study Designs call of the HTA Programme. Background: Cardiac rehabilitation is a process by which patients with heart disease, in partnership with health professionals, are encouraged and supported to achieve and maintain optimal physical health. The 2014 Cochrane systematic review and meta-analysis of randomised trials in heart failure shows that, compared with standard medical care, participation in exercise-based cardiac rehabilitation reduces the risk of heart failure specific hospitalisation and results in clinically meaningful improvements in patient health-related quality of life. Although recommended by the National Institute for Health and Care Excellence (NICE) and major international guidelines, current guidance does not reflect the possibility that exercise-based rehabilitation may confer differential effects across different heart failure patient subgroups. For example, patients with less severe disease or ejection fraction >45% may benefit more (or less) from rehabilitation than those with more severe disease or ejection fraction <=45%. The methodology of meta-analysis using individual patient data allows us to assess these subgroup effects with much more statistical power and precision than has been previously possible. Design and Methods: based on the comprehensive literature searches conducted by the 2014 Cochrane systematic review, we have obtained data from 28 randomised controlled trials in over 4,500 participants on which we will undertake an individual patient data meta-analysis. PPI: the project will take advantage of the PPI network that we have established in an ongoing NIHR funded programme of research. A patient with lived experience of heart failure will be an active member of the Project Steering Group. Dissemination: we will disseminate the results as openly and as widely as possible to clinical, managerial, patient, and policy groups to ensure our results are implemented widely and appropriately. Our results will help the NHS deliver more efficient patient treatment, better patient outcomes (enhanced quality of life and reduced risk of being admitted to hospital), and we anticipate will improve the uptake of cardiac rehabilitation services and maximise their cost-effectiveness.

Research activity codes: 6.7 PHYSICAL
Health categories: CARDIOVASCULAR