The Contribution of Individual Exercise Training Components to Clinical Outcomes in Randomised Controlled Trials of Cardiac Rehabilitation: A Systematic Review and Meta-regression

Abstract

Background: While the clinical benefits of exercise-based cardiac rehabilitation are well established, there is extensive variation in the interventions used within these trials. It is unknown whether variations in individual components of these exercise interventions provide different relative contributions to overall clinical outcomes. This study aims to systematically examine the relationship between individual components of the exercise intervention in cardiac rehabilitation (such as intensity and frequency) and clinical outcomes for people with coronary heart disease.

Methods: In this systematic review, eligible trials were identified via searches of databases (PubMed, Allied and Complementary Medicine, EMBASE, PEDro, Science Citation Index Expanded, CINAHL, The Cochrane Library, SPORTDiscus) from citation tracking and hand-searching. Studies were included if they were randomised trials of a structured exercise intervention (versus usual care) for participants with coronary heart disease and reported at least one of cardiovascular mortality, total mortality, myocardial infarction or revascularisation outcomes. Each included trial was assessed using the Cochrane Risk of Bias Tool. Authors were also contacted for missing intervention details or data. Random effects meta-analysis was performed to calculate a summary risk ratio (RR) with 95% confidence interval (CI) for the effect of exercise on outcomes. Random effects meta-regression and subgroup analyses were conducted to examine the association between pre-specified co-variates (exercise components or trial characteristics) and each clinical outcome.

Results: Sixty-nine trials were included, evaluating 72 interventions which differed markedly in terms of exercise components. Exercise-based cardiac rehabilitation was effective in reducing cardiovascular mortality (RR 0.74, 95% CI 0.65 to 0.86), total mortality (RR 0.90, 95% CI 0.83 to 0.99) and myocardial infarction (RR 0.80, 95% CI 0.70 to 0.92). This effect generally demonstrated no significant differences across subgroups of patients who received various types of usual care, more or less than 150 min of exercise per week and of differing cardiac aetiologies. There was however some heterogeneity observed in the efficacy of cardiac rehabilitation in reducing total mortality based on the presence of lipid lowering therapy (I ² = 48%, p = 0.15 for subgroup treatment interaction effect). No single exercise component was identified through meta-regression as a significant predictor of mortality outcomes, although reductions in both total (RR 0.81, p = 0.042) and cardiovascular mortality (RR 0.72, p = 0.045) were observed in trials which reported high levels of participant exercise adherence, versus those which reported lower levels. A dose-response relationship was found between an increasing exercise session time and increasing risk of myocardial infarction (RR 1.01, p = 0.011) and the highest intensity of exercise prescribed and an increasing risk of percutaneous coronary intervention (RR 1.05, p = 0.047).

Conclusions: Exercise-based cardiac rehabilitation is effective at reducing important clinical outcomes in patients with coronary heart disease. While our analysis was constrained by the quality of included trials and missing information about intervention components, there appears to be little differential effect of variations in exercise intervention, particularly on mortality outcomes. Given the observed effect between higher adherence and improved outcomes, it may be more important to provide exercise-based cardiac rehabilitation programs which focus on achieving increased adherence to the exercise intervention.

Fig. 1

PRISMA flow diagram of the screening and selection of trials. a Different type of exercise or surgical intervention as comparator. b We were unable to assess the eligibility of one trial published as a conference abstract as the author did not respond to repeated email inquiries. Two other conference abstracts described trials with outcomes eligible for inclusion; however, these could not be included as authors were not yet ready to share their results. One further abstract was eligible for inclusion; however, the author failed to respond to requests for data (abstract references in Additional file 1: Appendix S3). c One of these trials was later excluded and one included. CAD coronary artery disease, RCT randomised controlled trial

Fig. 2

Forest plot of the effect of exercise-based cardiac rehabilitation (vs usual care) on cardiovascular mortality across all types of interventions, CI confidence interval, CR cardiac rehabilitation

Fig. 3

Relationship between the reported level of exercise intervention adherence and the relative risk of cardiovascular mortality compared to usual care. Each intervention is represented by a circle; the size of the circle is proportional to the number of participants undertaking that intervention. A log RR of >0 represents an increase in risk and <0 a decrease

Fig. 4

The effect of exercise-based cardiac rehabilitation versus usual care on coronary heart disease outcomes. Diamonds represent the pooled summary estimate of random effects Mantel-Haenszel meta-analysis for each outcome. CR cardiac rehabilitation, UC usual care

Fig. 5

Relationship between the prescribed time for exercise training each session and the relative risk of myocardial infarction compared to usual care (p = 0.011). Each intervention is represented by a circle; the size of the circle is proportional to the number of participants undertaking that intervention. A log RR of >0 represents an increase in risk and <0 a decrease

Fig. 6

Relationship between the highest intensity of exercise prescribed (as a percentage of maximal heart rate) and the relative risk of percutaneous coronary intervention compared to usual care (p = 0.047). Each intervention is represented by a circle; the size of the circle is proportional to the number of participants undertaking that intervention. A log RR of >0 represents an increase in risk and <0 a decrease. Circles coloured green represent interventions for which the highest intensity was only prescribed for brief periods during interval training. Circles coloured purple represent interventions for which the highest intensity was only prescribed during the work periods of circuit training