This review assessed the heart rate variability change in coronary artery disease patients who received conventional secondary prevention by drugs, biobehavioural treatments and exercise training, concluding that significant moderate changes in heart rate variability change resulted from these interventions. The authors' conclusions reflect the evidence presented and are likely to be reliable.

To assess the heart rate variability change in coronary artery disease patients who received conventional secondary prevention by drugs, biobehavioural treatments and exercise training.

MEDLINE, PsycINFO, EMBASE and the Cochrane Library were searched without language restrictions from 1990 to July 2007; search terms were reported. Reference lists of retrieved studies were handsearched to identify any additional articles of interest.

Randomised controlled trials, with either a cross over or parallel group design, that compared at least 48 hours of pharmacotherapy, or at least two exercise sessions or biobehavioural treatments, with a control or placebo, in which heart rate variability was reported at baseline and following the intervention, were eligible for inclusion. Trials were restricted to coronary artery disease patients without comorbidities, although trials with chronic heart failure patients were permitted if an ischaemic aetiology was classified in at least 50% of patients. Trials in which the comparison group for coronary artery disease patients was a control group of healthy people were also excluded.

Eligible interventions comprised secondary prevention by drugs (beta-blockers, angiotensin converting enzyme inhibitors and calcium channel blockers), biobehavioural treatments (psychotropic medications, biofeedback and relaxation training) and exercise training.

The principal outcome was change in heart rate variability from baseline to post treatment; heart rate variability assessment in included studies was either ambulatory or laboratory-based.

The mean age of participants in the included trials ranged from 50.0 to 71.6 years and, where reported, between 59.3 to 100% of participants were male. Treatment duration ranged from one to 31 weeks.

The authors did not state how the papers were selected for the review or how many reviewers performed the selection.

Two reviewers independently assessed trial quality using previously published criteria in addition to method of patient selection, adequacy of randomisation, use of cross over design, duration of treatment, recording length of heart rate variability, ambulatory versus laboratory setting for heart rate variability assessment, and cointerventions. Disagreements were resolved through consensus.

Two reviewers independently extracted change in heart rate variability from baseline to post-treatment for each trial to calculate standardised mean differences (SMD); disagreements were resolved through consensus. An a priori hierarchy was used to select heart rate variability measures that represented the principal treatment effect for each trial, with priority given to frequency domain markers of vagal-heart rate modulation. Where both time and frequency domains were reported one of each, with the highest ranking on the heart rate variability selection hierarchy was extracted.

Standardised mean differences and 95% confidence intervals (CIs) using a modified Hedges' g statistic were pooled using a random-effects meta-analysis using an intention-to-treat analysis. The analysis was stratified by the three major classes of intervention and, where more than two treatment arms were compared, comparisons were weighted by the size of the treatment group. Cohen's d criteria were used to determine the magnitude of the pooled standardised mean difference (below 0.2 was small, 0.2 to 0.5 was moderate and above 0.5 was large).

Multivariate analyses were used to jointly analyse the two types of outcome (time and frequency domain indices). Statistical heterogeneity between trials was assessed using the Q statistic. A sensitivity analysis inverting the heart rate variability hierarchy was carried out so that time domain heart rate variability indices were prioritised over frequency domain indices. Meta-regression was used to explore potential reasons for heterogeneity caused by: cointerventions; crossover versus parallel group design; active versus placebo control; laboratory versus ambulatory heart rate variability recording; trial quality; mean age of cohort; duration of therapy; and methodological or statistical control for confounding factors. Publication bias was assessed through a funnel plot.

A total of 33 RCTs (n=1,686 patients; range 8 to 258) were included in the review. No publication bias was detected. The majority of trials were reported as good quality.

Over all treatments, compared to control groups, there was a significant increase in heart rate variability (SMD 0.40, 95% CI 0.28 to 0.52). Across intervention classes significant increases in heart rate variability were also noted for pharmacologic interventions (SMD 0.50, 95% CI 0.30 to 0.70; 15 comparisons), behavioural treatments (SMD 0.31, 95% CI 0.06 to 0.57; seven RCTs) and exercise (SMD 0.36, 95% CI 0.18 to 0.55; 16 RCTs), as well as for a composite of time and frequency domain indices (SMD=0.40) or separate time (SMD=0.37) or frequency indices (SMD=0.43). There was no significant heterogeneity for these comparisons.

The pooled treatment effect of 0.40 was equivalent to an increase in standard deviation of all normal-to-normal R-R intervals of 9.0 milliseconds (95% CI 7.3 to 10.7) or a relative increase of 15.9% (95% CI 13.2 to 18.6).

Sensitivity analyses and meta-regressions confirmed the robustness of the analyses.

Moderate increases in heart rate variability resulted from secondary prevention in coronary artery disease with medication, biobehavioral treatments and exercise.

The review question and inclusion criteria were clear. A thorough search for studies with no language restrictions was undertaken, reducing the likelihood of language bias. There was no apparent search for unpublished studies, so some studies may have been missed. Publication were extracted from all trials. Publication bias was assessed and none was detected. More than one reviewer was involved in the data extraction, but it was not clear whether this extended to study selection.

Appropriate criteria were used to assess the quality of the included trials; most were reported by the authors to be of ‘good quality’, but the results did not appear to be reported in the review. The extraction of outcomes in a hierarchical manner may mean that not all outcomes being evaluated were extracted from all trials. The majority of the included trials were small and contained less than 40 subjects. Appropriate methods appear to have been employed for the meta-analysis, with suitable methods undertaken to assess statistical heterogeneity.

Despite some shortcomings in the review process and small sample sizes, the authors' conclusions accurately reflect the evidence presented and are likely to be reliable.

Practice: The authors did not state implications for practice.

Research: The authors stated that heart rate variability research should evaluate the impact of improving heart rate variability on coronary artery disease prognosis and quantify heart rate variability improvement on based on present and new classes of pharmacologic treatment and behavioural interventions, both alone and in combination.

Not stated.

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.