Exercise training for chronic heart failure (ExTraMATCH II): individual participant data meta-analysis of randomised controlled trials
Taylor, R; Walker, S; Ciani, O; et al.Warren, F; Smart, N; Piepoli, M; Davos, C
Date: 29 May 2019
Publisher
NIHR Journals Library
Publisher DOI
Abstract
Background: Current national and international guidelines on the management of heart failure (HF) recommend exercise-based cardiac rehabilitation (ExCR), but do not differentiate this recommendation according to patient subgroups.
Objective(s): (1) to obtain definitive estimates of the impact of ExCR interventions versus control (no ...
Background: Current national and international guidelines on the management of heart failure (HF) recommend exercise-based cardiac rehabilitation (ExCR), but do not differentiate this recommendation according to patient subgroups.
Objective(s): (1) to obtain definitive estimates of the impact of ExCR interventions versus control (no exercise intervention) on mortality, hospitalisation, exercise capacity, and health-related quality of life (HRQoL) in HF patients; (2) to determine the differential (subgroup) effects of ExCR in HF patients according to their age, gender, ejection fraction, aetiology, New York Heart Association (NYHA) class, and baseline exercise capacity; (3) to assess whether the change in exercise capacity mediates for the impact of the ExCR on final outcomes (mortality, hospitalisation, and HRQoL) and is an acceptable surrogate endpoint.
Design: Individual participant data (IPD) meta-analysis
Setting: An international literature review
Participants: HF patients in randomised controlled trials (RCTs) of ExCR
Interventions: ExCR for at least 3 weeks compared with no exercise control with 6 months follow-up
Main outcome measures: mortality (all cause and HF-specific), hospitalisation (all-cause & HF-specific), exercise capacity, and HRQoL
Data sources: Individual participant data from eligible RCTs
3
Review methods: RCTs from ExTraMATCH IPD meta-analysis and 2014 Cochrane systematic review of ExCR
Results: Out of the 23 eligible RCTs (4,398 patients), 19 RCTs (3,990 patients) contributed data to this IPD meta-analysis. There was a wide variation in exercise programme prescriptions across included studies. Compared with control, there was no statistically significant difference in pooled time to event estimates in favour of ExCR although confidence intervals were wide: all-cause mortality: hazard ratio (HR) 0.83 (95% confidence interval (CI): 0.67 to 1.04), HF-related mortality: HR 0.84 (95% CI: 0.49 to 1.46), all-cause hospitalisation: HR 0.90 (95% CI: 0.76 to 1.06), and HF-related hospitalisation: HR 0.98 (95% CI: 0.72 to 1.35). There was a statistically significant difference in favour of ExCR for exercise capacity and HRQoL. Compared to control, at 12-months follow-up, improvements were seen in the six-minute walk test (6MWT) (mean: 21.0 metres, 95% CI: 1.57 to 40.4, and Minnesota Living with HF Questionnaire score (mean: -5.94, 95% CI: -1.0 to -10.9, lower scores indicate improved HRQoL). No strong evidence for differential intervention effects across patient characteristics was found for any outcomes. Moderate to good levels of correlation (R2 trial>50% & ρ>0.50) between peak oxygen uptake (VO2peak) or 6MWT with mortality and HRQoL were seen. Estimated surrogate threshold effect (STE) was an increase of 1.6 to 4.6 ml/kg/min for VO2peak.
Limitations: Lack consistency in how included RCTs defined and collected the outcomes; we were unable to obtain IPD from all includable trials for all outcomes; and we did not seek patient level on exercise adherence. .
Conclusions: In comparison to no exercise control, participation in ExCR improves the exercise and HRQoL in HF patients but appears to have no effect on their mortality or hospitalisation. No strong evidence was found of differential intervention effects of ExCR across patient characteristics. VO2peak and 6MWT may be suitable surrogate endpoints for the treatment effect of ExCR on mortality and HRQoL in HF.
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