Impact of Exercise Rehabilitation on Exercise Capacity and Quality-of-Life in Heart Failure: Individual Participant Meta-Analysis.
Previous systematic reviews have indicated that exercise-based cardiac rehabilitation (ExCR) for patients with heart failure (HF) has a beneficial effect on health-related quality-of-life (HRQoL) and exercise capacity. However, there is uncertainty regarding potential differential effects of ExCR across HF patient subgroups.
The authors sought to undertake an individual participant data (IPD) meta-analysis to: 1) assess the impact of ExCR on HRQoL and exercise capacity in patients with HF; and 2) investigate differential effects of ExCR according to a range of patient characteristics: age, sex, ethnicity, New York Heart Association functional class, ischemic etiology, ejection fraction, and exercise capacity.
A single dataset was produced, comprising randomized trials where ExCR (delivered for 3 weeks or more) was compared with a no exercise control group. Each trial provided IPD on HRQoL or exercise capacity (or both), with follow-up of 6 months or more. One- and 2-stage meta-analysis models were used to investigate the effect of ExCR overall and the interactions between ExCR and participant characteristics.
IPD was obtained from 13 trials for 3,990 patients, predominantly (97%) with reduced ejection fraction HF. Compared with the control group, there was a statistically significant difference in favor of ExCR for HRQoL and exercise capacity. At 12-month follow-up, improvements were seen in 6-min walk test (mean 21.0 m; 95% confidence interval: 1.57 to 40.4 m; p = 0.034) and Minnesota Living With HF score (mean improvement 5.9; 95% confidence interval: 1.0 to 10.9; p = 0.018). No consistent evidence was found of differential intervention effects across patient subgroups.
These results, based on an IPD meta-analysis of randomized trials, confirm the benefit of ExCR on HRQoL and exercise capacity and support the Class I recommendation of current international clinical guidelines that ExCR should be offered to all HF patients. (Exercise Training for Chronic Heart Failure [ExTraMATCH II]: protocol for an individual participant data meta-analysis; PROSPERO: international database of systematic reviews CRD42014007170).
Taylor RS
，Walker S
，Smart NA
，Piepoli MF
，Warren FC
，Ciani O
，Whellan D
，O'Connor C
，Keteyian SJ
，Coats A
，Davos CH
，Dalal HM
，Dracup K
，Evangelista LS
，Jolly K
，Myers J
，Nilsson BB
，Passino C
，Witham MD
，Yeh GY
，ExTraMATCH II Collaboration
... -
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Impact of exercise-based cardiac rehabilitation in patients with heart failure (ExTraMATCH II) on mortality and hospitalisation: an individual patient data meta-analysis of randomised trials.
To undertake an individual patient data (IPD) meta-analysis to assess the impact of exercise-based cardiac rehabilitation (ExCR) in patients with heart failure (HF) on mortality and hospitalisation, and differential effects of ExCR according to patient characteristics: age, sex, ethnicity, New York Heart Association functional class, ischaemic aetiology, ejection fraction, and exercise capacity.
Randomised trials of exercise training for at least 3 weeks compared with no exercise control with 6-month follow-up or longer, providing IPD time to event on mortality or hospitalisation (all-cause or HF-specific). IPD were combined into a single dataset. We used Cox proportional hazards models to investigate the effect of ExCR and the interactions between ExCR and participant characteristics. We used both two-stage random effects and one-stage fixed effect models. IPD were obtained from 18 trials including 3912 patients with HF with reduced ejection fraction. Compared to control, there was no statistically significant difference in pooled time to event estimates in favour of ExCR although confidence intervals (CIs) were wide [all-cause mortality: hazard ratio (HR) 0.83, 95% CI 0.67-1.04; HF-specific mortality: HR 0.84, 95% CI 0.49-1.46; all-cause hospitalisation: HR 0.90, 95% CI 0.76-1.06; and HF-specific hospitalisation: HR 0.98, 95% CI 0.72-1.35]. No strong evidence was found of differential intervention effects across patient characteristics.
Exercise-based cardiac rehabilitation did not have a significant effect on the risk of mortality and hospitalisation in HF with reduced ejection fraction. However, uncertainty around effect estimates precludes drawing definitive conclusions.
Taylor RS
，Walker S
，Smart NA
，Piepoli MF
，Warren FC
，Ciani O
，O'Connor C
，Whellan D
，Keteyian SJ
，Coats A
，Davos CH
，Dalal HM
，Dracup K
，Evangelista L
，Jolly K
，Myers J
，McKelvie RS
，Nilsson BB
，Passino C
，Witham MD
，Yeh GY
，Zwisler AO
，ExTraMATCH II Collaboration
... -
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Exercise-based cardiac rehabilitation for adults with heart failure.
People with heart failure experience substantial disease burden that includes low exercise tolerance, poor health-related quality of life (HRQoL), increased risk of mortality and hospital admission, and high healthcare costs. The previous 2018 Cochrane review reported that exercise-based cardiac rehabilitation (ExCR) compared to no exercise control shows improvement in HRQoL and hospital admission amongst people with heart failure, as well as possible reduction in mortality over the longer term, and that these reductions appear to be consistent across patient and programme characteristics. Limitations noted by the authors of this previous Cochrane review include the following: (1) most trials were undertaken in patients with heart failure with reduced (< 45%) ejection fraction (HFrEF), and women, older people, and those with heart failure with preserved (≥ 45%) ejection fraction (HFpEF) were under-represented; and (2) most trials were undertaken in a hospital or centre-based setting.
To assess the effects of ExCR on mortality, hospital admission, and health-related quality of life of adults with heart failure.
We searched CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO and Web of Science without language restriction on 13 December 2021. We also checked the bibliographies of included studies, identified relevant systematic reviews, and two clinical trials registers.
We included randomised controlled trials (RCTs) that compared ExCR interventions (either exercise only or exercise as part of a comprehensive cardiac rehabilitation) with a follow-up of six months or longer versus a no-exercise control (e.g. usual medical care). The study population comprised adults (≥ 18 years) with heart failure - either HFrEF or HFpEF.
We used standard Cochrane methods. Our primary outcomes were all-cause mortality, mortality due to heart failure, all-cause hospital admissions, heart failure-related hospital admissions, and HRQoL. Secondary outcomes were costs and cost-effectiveness. We used GRADE to assess the certainty of the evidence.
We included 60 trials (8728 participants) with a median of six months' follow-up. For this latest update, we identified 16 new trials (2945 new participants), in addition to the previously identified 44 trials (5783 existing participants). Although the existing evidence base predominantly includes patients with HFrEF, with New York Heart Association (NYHA) classes II and III receiving centre-based ExCR programmes, a growing body of trials includes patients with HFpEF with ExCR undertaken in a home-based setting. All included trials employed a usual care comparator with a formal no-exercise intervention as well as a wide range of active comparators, such as education, psychological intervention, or medical management. The overall risk of bias in the included trials was low or unclear, and we mostly downgraded the certainty of evidence of outcomes upon GRADE assessment. There was no evidence of a difference in the short term (up to 12 months' follow-up) in the pooled risk of all-cause mortality when comparing ExCR versus usual care (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.71 to 1.21; absolute effects 5.0% versus 5.8%; 34 trials, 36 comparisons, 3941 participants; low-certainty evidence). Only a few trials reported information on whether participants died due to heart failure. Participation in ExCR versus usual care likely reduced the risk of all-cause hospital admissions (RR 0.69, 95% CI 0.56 to 0.86; absolute effects 15.9% versus 23.8%; 23 trials, 24 comparisons, 2283 participants; moderate-certainty evidence) and heart failure-related hospital admissions (RR 0.82, 95% CI 0.49 to 1.35; absolute effects 5.6% versus 6.4%; 10 trials; 10 comparisons, 911 participants; moderate-certainty evidence) in the short term. Participation in ExCR likely improved short-term HRQoL as measured by the Minnesota Living with Heart Failure (MLWHF) questionnaire (lower scores indicate better HRQoL and a difference of 5 points or more indicates clinical importance; mean difference (MD) -7.39 points, 95% CI -10.30 to -4.77; 21 trials, 22 comparisons, 2699 participants; moderate-certainty evidence). When pooling HRQoL data measured by any questionnaire/scale, we found that ExCR may improve HRQoL in the short term, but the evidence is very uncertain (33 trials, 37 comparisons, 4769 participants; standardised mean difference (SMD) -0.52, 95% CI -0.70 to -0.34; very-low certainty evidence). ExCR effects appeared to be consistent across different models of ExCR delivery: centre- versus home-based, exercise dose, exercise only versus comprehensive programmes, and aerobic training alone versus aerobic plus resistance programmes.
This updated Cochrane review provides additional randomised evidence (16 trials) to support the conclusions of the previous 2018 version of the review. Compared to no exercise control, whilst there was no evidence of a difference in all-cause mortality in people with heart failure, ExCR participation likely reduces the risk of all-cause hospital admissions and heart failure-related hospital admissions, and may result in important improvements in HRQoL. Importantly, this updated review provides additional evidence supporting the use of alternative modes of ExCR delivery, including home-based and digitally-supported programmes. Future ExCR trials need to focus on the recruitment of traditionally less represented heart failure patient groups including older patients, women, and those with HFpEF.
Molloy C
，Long L
，Mordi IR
，Bridges C
，Sagar VA
，Davies EJ
，Coats AJ
，Dalal H
，Rees K
，Singh SJ
，Taylor RS
... -
《Cochrane Database of Systematic Reviews》
ResearchGate
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