Validation of Exercise Capacity as a Surrogate Endpoint in Exercise-Based Rehabilitation for Heart Failure: A Meta-Analysis of Randomized Controlled Trials

Title
Validation of Exercise Capacity as a Surrogate Endpoint in Exercise-Based Rehabilitation for Heart Failure: A Meta-Analysis of Randomized Controlled Trials
Publication Date
2018
Author(s)
Ciani, Oriana
Piepoli, Massimo
Smart, Neil
( author )
OrcID: https://orcid.org/0000-0002-8290-6409
Email: nsmart2@une.edu.au
UNE Id une-id:nsmart2
Uddin, Jamal
Walker, Sarah
Warren, Fiona C
Zwisler, Ann D
Davos, Constantinos H
Taylor, Rod S
Type of document
Journal Article
Language
en
Entity Type
Publication
Publisher
Elsevier Inc
Place of publication
United States of America
DOI
10.1016/j.jchf.2018.03.017
UNE publication id
une:23728
Abstract
OBJECTIVES This study sought to validate exercise capacity (EC) as a surrogate for mortality, hospitalization, and health-related quality of life (HRQOL). BACKGROUND EC is often used as a primary outcome in exercise-based cardiac rehabilitation (CR) trials of heart failure (HF) via direct cardiorespiratory assessment of maximum oxygen uptake (Vo₂peak) or through submaximal tests, such as the 6-min walk test (6MWT). METHODS After a systematic review, 31 randomized trials of exercise-based CR compared with no exercise control (4,784 HF patients) were included. Outcomes were pooled using random effects meta-analyses, and inverse variance weighted linear regression equations were fitted to estimate the relationship between the CR on EC and all-cause mortality, hospitalization, and HRQOL. Spearman correlation coefficient (r), R2 at trial level, and surrogate threshold effect (STE) were calculated. STE represents the intercept of the prediction band of the regression line with null effect on the final outcome. RESULTS Exercise-based CR is associated with positive effects on EC measured through Vo₂peak (þ3.10 ml/kg/min; 95% confidence interval [CI]: 2.01 to 4.20) or 6MWT (þ41.15 m; 95% CI: 16.68 to 65.63) compared to control. The analyses showed a low level of association between improvements in EC (Vo₂peak or 6MWT) and mortality and hospitalization. Moderate levels of correlation between EC with HRQOL were seen (e.g., R2 <52%; jrj < 0.72). Estimated STE was an increase of 5 ml/kg/min for Vo₂peak and 80 m for 6MWT to predict a significant improvement in HRQOL. CONCLUSIONS The study results indicate that EC is a poor surrogate endpoint for mortality and hospitalization but has moderate validity as a surrogate for HRQOL. Further research is needed to confirm these findings across other HF interventions.
Link
Citation
JACC: Heart Failure, 6(7), p. 596-604
ISSN
2213-1787
2213-1779
Start page
596
End page
604

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