Cardiac rehabilitation for people with heart disease: an overview of Cochrane systematic reviews

  • Protocol
  • Overview

Authors


Abstract

This is a protocol for a Cochrane Review (Overview). The objectives are as follows:

The primary aim of this overview is to summarise the research question, methods and findings of the Cochrane reviews on cardiac rehabilitation (CR) and to provide a 'friendly front end' to this portfolio of reviews. In addition, we will aim to:

  1. Identify the opportunities for merging and splitting across the reviews to inform the direction of future Cochrane CR review updates;

  2. Identify key evidence gaps across the reviews to inform de novo Cochrane CR reviews; and

  3. Identify disparities in current reporting outputs and provide recommendations to encourage uniformity of reporting of future trials and systematic reviews.

Background

Description of the condition

Heart disease is a broad term used to describe a range of diseases that affect the heart. The various diseases that fall under the umbrella of heart disease include diseases of heart blood vessels (coronary artery disease), heart rhythm problems (arrhythmias), heart infections and congenital heart defects. Coronary heart disease (CHD) is the most common type of heart disease and its common symptoms are chest pain (angina) and heart attack (myocardial infarction). Acute coronary syndrome refers to a range of acute CHD states and includes unstable angina (chest pain at rest), non-ST segment elevation myocardial infarction (ST segment elevation generally absent), and ST segment elevation infarction (persistent ST segment elevation usually present). CHD can result in difficulties in functionality and performance of everyday activities and can impair sexual function (Racca 2010), contributing to a reduction in health-related quality of life (HRQL) (Gravely-Witte 2007).

CHD is now considered to be the leading cause of global mortality. According to the World Health Organisation, CHD accounted for 12.9% of all deaths (7 million deaths) and 5.8% of total disability-adjusted life years globally in 2011 (WHO 2014). The situation is worse in high income countries, and it has been estimated that CHD accounted for 24.8% of all deaths in Europe in 2011 (WHO 2014). However, despite the overall increase in CHD burden in high income countries, the age-adjusted death rates for this disease are declining and over half of those diagnosed now survive (Allender 2008). This is driven largely by preventive interventions, treatments to prevent death during an acute disease manifestation and rehabilitation interventions that prolong survival (Gaziano 2010). Conversely, morbidity is on the rise, with an increasing number of survivors of myocardial infarction (Mathers 2008) and an associated number of cases of chronic heart failure (HF) (Kostis 1997).

The most common cause of heart failure (HF) is CHD. Non-ischaemic causes of HF include hypertension and atrial fibrillation. HF is a complex clinical syndrome that results from any structural or functional impairment of ventricular filling or ejection of blood. It has been increasingly recognised that HF has two sub-categories: (i) impaired left ventricular contraction, which results in a reduced ejection fraction (< 35% to 50%), known as HF with reduced ejection fraction (HFREF) or ‘systolic HF’; and (ii) HF with preserved ejection fraction (HFPEF) with an ejection fraction of > 35% to 50% and also known as ‘diastolic HF'. Patients with HF experience marked reductions in their exercise capacity which has detrimental effects on their activities of daily living, HRQL, their hospital admission rate and mortality (Go 2014). In high income countries, around 2% of adults suffer from HF, but in those over the age of 65, this increases to 6% to 10% (McMurray 2005; Dickstein 2008). The prevalence and incidence of HF is steadily increasing, with approximately 825,000 new cases annually in the United Sates (Go 2014). HF has a poor prognosis, with 30% to 40% of those diagnosed dying within a year, although thereafter the mortality is less than 10% per year (Cowie 2000; Hobbs 2007). However, as with CHD, survival after HF diagnosis has also improved (Go 2014), and in the United Kingdom (UK) there is evidence of a trend of improved prognosis, with the six month mortality rate decreasing from 26% in 1995 to 14% in 2005 (Mehta 2009).

Description of the interventions

Many definitions of cardiac rehabilitation (CR) have been proposed. The following definition encompasses the key concepts of CR: “The coordinated sum of activities required to influence favourably the underlying cause of cardiovascular disease, as well as to provide the best possible physical, mental and social conditions, so that the patients may, by their own efforts, preserve or resume optimal functioning in their community and through improved health behaviour, slow or reverse progression of disease” (BACPR 2012). Whilst exercise training is a cornerstone of CR, it is recommended that 'comprehensive' programmes also include education (e.g. provision of information about a healthy lifestyle) and psychological intervention (e.g. counselling to reduce stress). CR has many of the characteristics of a 'complex intervention' as defined by in the Medical Research Council 2008 guidance for developing and evaluating complex interventions, i.e. (1) number of interacting components; (2) number and difficulty of behaviours required by those delivering or receiving the intervention; (3) number and variability of outcomes; and (4) degree of flexibility or tailoring of the intervention permitted (non-standardisation / reproducibility) (Craig 2008).

Patient education is the process by which health professionals impart information to patients that will alter their health behaviours or improve their health status (Koongstvedt 2001). There is substantial variation in the delivery of patient education for cardiac patients; it may be classroom- or home-based, group or individual, tailored or generic. Duration and reinforcement of education also differs between programmes. Some programmes are developed according to validated educational theory and by trained professionals whilst others are delivered by peers.

Interventions which specifically aim to influence psychological or psychosocial outcomes are varied and may range from organisational efforts to improve patient communication and support e.g. Jolly et al (Jolly 1998), to empirically supported psychotherapies used to target diagnosed psychopathology in cardiac patients e.g. Black et al (Black 1998). Furthermore psychological/psychosocial interventions may incorporate other elements of CR such as diet and lifestyle advice, or exercise. In some cases the intervention may be described as ‘psychological’ only to the extent that psychological techniques are used to further other treatment goals.

The patient groups routinely recommended for CR include those with post-myocardial infarction, post revascularisation procedure, and HF. Traditionally, CR programmes have been offered in a supervised centre-based setting. However, many patients fail to receive rehabilitation (Bethell 2008) and current uptake of CR for both CHD and HF appears to be sub-optimal (Tierney 2011; Dalal 2012; NICE 2013). Home-based CR programmes have been increasingly introduced to widen access and participation. In addition to uptake, maintaining longer term adherence to CR is also a key challenge (Daly 2002; Moore 2003) and therefore interventions aimed at improving patient uptake and adherence to CR programmes have been adopted and will also be investigated in this overview.

Based on current evidence, national and international guidelines on the management of CHD and HF including those by the American College of Cardiology/American Heart, European Society of Cardiology and National Institute for Health and Care Excellence (NICE) in the UK, consistently recommend CR as an effective and safe intervention (NICE 2010; McMurray 2012; NICE 2013; Yancy 2013).

How the intervention might work

The mechanism by which CR might work depends on the patient group and the component of rehabilitation being considered. The majority of mechanistic evidence is for exercise training.

For those with CHD, exercise training has been shown to have direct benefits on the heart and coronary vasculature, including myocardial oxygen demand, endothelial function, autonomic tone, coagulation and clotting factors, inflammatory markers, and the development of coronary collateral vessels (Clausen 1976; Hambrecht 2000). However, findings of the original Cochrane review of exercise based CR for CHD (Jolliffe 2001) supported the hypothesis that reductions in mortality may also be mediated via the indirect effects of exercise through improvements in the risk factors for atherosclerotic disease (i.e. lipids, smoking and blood pressure) (Taylor 2006).

The precise mechanism(s) through which exercise training benefits patients with HF remains unclear. One explanation, applicable to patients with ischaemic causes of HF, is that exercise training improves myocardial perfusion by alleviating endothelial dysfunction therefore dilating coronary vessels and by stimulating new vessel formation by way of intermittent ischaemia (Piepoli 2004). Indeed, Belardinelli and colleagues have demonstrated that aerobic training improves myocardial contractility and diastolic filling (Belardinelli 1998). A meta-analysis by Haykowsky et al demonstrated the benefits of exercise training on cardiac remodelling as measured by ejection fraction, end-diastolic volume, and end-systolic volume (Haykowsky 2007). Regardless of cause, there are important neurohormonal and musculoskeletal abnormalities in HF. Exercise training may reduce adrenergic tone and increase vagal tone, as suggested by an assessment of variability in heart rate. Skeletal muscle dysfunction and wasting may also respond to exercise training (Piepoli 2004). Hambrecht et al have demonstrated that regular physical activity in HF patients stimulates vasodilatation in the skeletal muscle vasculature (Hambrecht 1998).

The benefits of education and psychological interventions depend on patient behaviour change including improvements in healthy lifestyle and changes in mood, such as reductions in depression and anxiety.

Why it is important to do this overview

In 2001, Jolliffe et al published the first Cochrane review of CR, summarising the evidence of 32 randomised controlled trials (RCTs) in 8440 post-myocardial infarction and revascularisation patients, and confirming a mortality benefit of exercise-based CR (Jolliffe 2001). With the funding support of the National Institute of Health Research (NIHR) in United Kingdom, over the last 10 years the portfolio of published Cochrane reviews has grown to six systematic reviews/meta-analyses:

  • Exercise based rehabilitation for heart failure (Taylor 2014a);

  • Home-based versus centre-based cardiac rehabilitation (Taylor 2014b);

  • Exercise-based cardiac rehabilitation for coronary heart disease (Heran 2011);

  • Psychological interventions for coronary heart disease (Whalley 2011);

  • Patient education in the management of coronary heart disease (Brown 2011);

  • Promoting patient uptake and adherence in cardiac rehabilitation (Karmali 2014).

The development of the portfolio of Cochrane reviews has reflected many of the key areas of evolution in the provision of CR and how this model of service delivery can differ across international healthcare jurisdictions i.e. the shift from emphasis on exercise therapy alone to comprehensive secondary prevention including risk factor and dietary education and management of psychological factors; the expansion of the population of cardiac patients receiving CR services to include heart failure; the development of alternative settings of CR delivery that include home provision in addition to the traditional supervised hospital- or centre-based programmes; and the need to broaden the consideration of the outcomes of CR to inform the needs of healthcare policy makers (e.g. impacts on hospital admission, HRQL, and healthcare costs). This Cochrane CR review portfolio remains dynamic, with 3 reviews having undergone an update in the last 12 months (Karmali 2014; Taylor 2014a; Taylor 2014b).

The portfolio of Cochrane reviews has played an important role in informing evidence-based policy for CR nationally and internationally, and the reviews have been cited in a number of key clinical guidelines including those by the American College of Cardiology/American Heart, European Society of Cardiology and NICE in the UK, that consistently recommend CR as a safe and effective intervention (NICE 2010; McMurray 2012; NICE 2013; Yancy 2013).

Overviews of systematic reviews (overviews) are a new approach to summarising evidence, synthesising results from multiple systematic reviews into a single usable document (Becker 2011). By providing a single synthesis of all relevant evidence in a particular area, overviews may be useful for therapeutic and policy decision-making, providing a comprehensive ‘friendly front end’ to the evidence, so that the reader does not have to assimilate the data from separate systematic reviews. Overviews can also help inform the strategic direction of conduct and structuring of future systematic reviews. For example, the latest version of the Cochrane review of exercise based CR for CHD includes 47 RCTs in over 10,000 patients and may therefore benefit from being organised into sub-reviews ('splitting') according to CHD indications i.e. post-myocardial infarction, revascularisation and angina. Finally, overviews provide an opportunity to identify potential 'evidence gaps' and therefore inform areas in which new Cochrane reviews should be prioritised.

Objectives

The primary aim of this overview is to summarise the research question, methods and findings of the Cochrane reviews on cardiac rehabilitation (CR) and to provide a 'friendly front end' to this portfolio of reviews. In addition, we will aim to:

  1. Identify the opportunities for merging and splitting across the reviews to inform the direction of future Cochrane CR review updates;

  2. Identify key evidence gaps across the reviews to inform de novo Cochrane CR reviews; and

  3. Identify disparities in current reporting outputs and provide recommendations to encourage uniformity of reporting of future trials and systematic reviews.

Methods

This overview will be conducted in accordance with the recommendations for Cochrane overviews (Becker 2011).

Criteria for considering reviews for inclusion

We will initially include the portfolio of six Cochrane CR reviews listed above which are already known to us. In addition, we will seek to include any other Cochrane systematic reviews that may inform the aims of this overview including those which assess the efficiency of CR services or which compare the delivery of CR across different settings.

Types of reviews

We will include Cochrane reviews and protocols currently published in The Cochrane Library that examine the impact of CR. Given the targeted aims of this overview we do not intend to consider non-Cochrane systematic reviews.

Types of participants

We will seek to include adults aged 18 or over, with heart disease, regardless of etiology.

Types of interventions

For the purposes of this review, CR is defined as: "Exercise with or without education and / or psychological intervention, delivered to patients with heart disease, in a hospital community or a home-based setting".

Types of outcome

The following outcomes will be considered:

Patient-related outcomes
  • Mortality

    • Cardiovascular mortality and non-cardiovascular mortality

  • Morbidity

    • Myocardial infarction (MI) (total MI, fatal MI and non-fatal MI)

    • Total revascularisations (coronary artery bypass graft (CABG), percutaneous transluminal coronary angioplasty (PTCA) and re-stenting)

    • Total hospitalisations (cardiovascular hospitalisations and other hospitalisations)

    • Health-related quality of life assessed using validated instruments (e.g. SF-36, EQ5D)

Process-related outcomes
  • Measure of uptake of, or adherence to, CR

  • Costs and cost-effectiveness

Search methods for identification of reviews

We will search the Cochrane Database of Systematic Reviews on The Cochrane Library (latest issue) using the search strategy in Appendix 1. We will not apply any date or language restrictions. All protocols for ongoing reviews will be noted in the ‘Studies awaiting assessment’ section for possible inclusion in future updates of this overview.

Data collection and analysis

Selection of reviews

Two authors (LA, RST) will independently screen for inclusion the titles and abstracts of all of the Cochrane systematic reviews we identify as a result of the search, and code them as 'retrieve' (eligible or potentially eligible/unclear) or 'do not retrieve'. If there are any disagreements, we will invite a third person to arbitrate. We will retrieve the full-text reviews and two authors (LA, RST) will independently screen the full-text and identify reviews for inclusion, and identify and record reasons for exclusion of the ineligible reviews. We will resolve any disagreement through discussion or, if required, we will consult a third person. We will record the selection process in sufficient detail to complete a PRISMA flow diagram and 'Characteristics of excluded reviews' table.

Data extraction and management

We will use a data collection form for characteristics of reviews included in the overview. This form will be piloted on at least one review included in the overview. One author (LA) will extract review characteristics from included reviews and a second author (RST) will check all extracted data for accuracy. The data extracted will include review objectives, search time frame, inclusion criteria (study design, population, intervention, comparator and outcomes), study limitations, source of funding, and stated conflicts of interest of review authors.

A second data collection form will be used to extract and summarise characteristics of studies included in each of the Cochrane reviews. This form will be piloted on at least one review included in the overview. One author (LA) will extract study characteristics from included studies and a second author (RST) will check all extracted data for accuracy. The data extracted will include number of included RCTs, year of publication, methods (population, intervention and comparator, primary and secondary outcomes specified and collected, total duration of study, number of study centres and location).

One author (LA) will independently extract all outcome data from included studies and a second author (RST) will check all extracted data for accuracy. We will resolve disagreements by consensus or by inviting a third person to arbitrate. One author (LA) will transfer data into the RevMan 2014 file. A second author (RST) will spot-check review characteristics for accuracy against the Cochrane review. Further content will be extracted for the purposes of a narrative summary and discussion.

Assessment of risk of bias in included reviews

We will not reassess the risk of bias of included studies within reviews but instead report study quality according to the review authors’ assessment using the Cochrane 'Risk of bias' tool (in accordance with the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). The standard 'Risk of bias' items include: random sequence generation and allocation concealment, description of drop-outs and withdrawals, blinding of outcome assessment and presence of selective reporting. In addition, evidence will be sought that the groups were balanced at baseline, that an intention-to-treat analysis was undertaken and that groups received comparable care (apart from the intervention). Where a 'Risk of bias' element was not reported within the review, the original included study publication will be assessed by a single author (LA) and checked by a second author (RST).

'Characteristics of included reviews’ tables

We plan to prepare several ‘Characteristics of included reviews’ tables to present data extracted on the characteristics of included reviews; the characteristics of trials included in the reviews; the methodological quality of included reviews (R-AMSTAR ratings) and the risk of bias of included reviews.

Dealing with missing data

We will report outcomes presented within the included Cochrane systematic reviews in this overview. If any information from the reviews is unclear or missing, we will look at the published reports of the individual trials and contact individual authors if necessary.

Assessment of methodological quality of included reviews

Quality of included reviews

One author (LA) will independently assess the methodological quality of the included reviews using the ‘Revised Assessment of Multiple Systematic Reviews’ (R-AMSTAR) measurement tool (Kung 2010), where the 11 domains will be scored between 1 and 4. The assessment will be checked by a second reviewer (RST) and any disagreements will be resolved by discussion. We will not exclude Cochrane reviews on the basis of methodological quality.

Quality of evidence in included reviews

We will used the GRADE framework to assess the quality of evidence for outcomes reported in each of the reviews, based on the following factors: indirectness of evidence, unexplained heterogeneity, publication bias, risk of bias due to study design limitations, and imprecision of results (Balshem 2011).

Assessment of bias in conducting the overview

We will conduct the overview according to this published protocol and report any deviations from it in the 'Differences between protocol and review' section of the overview.

Data synthesis

The unit of analysis for this overview is the systematic reviews (and not individual trials). The focus of the data presentation is descriptive, with detailed tabular presentations of the extracted review- and trial-level information outlined above. We have not conducted any de novo data analysis of trial-level outcomes for this overview. We extracted and tabulated review-level summaries for all the outcomes listed above, from each of the included reviews. Where outcomes were meta-analysed, we have extracted and reported pooled effect sizes. Where no quantitative pooling of effect sizes has been reported, or where outcomes are reported descriptively by single studies, we have reported these results by vote counting (Bushman 1984), or using standardised language indicating direction of effect and statistical significance. For continuous outcomes, data is summarised using the standardised mean difference (SMD) or mean difference (MD) with 95% confidence interval (CI) as reported in the included reviews. For dichotomous outcomes, relative risk (RR) or odds ratio (OR) and 95% CI are presented as appropriate.

Due to the heterogeneity of populations, interventions and outcomes in the included systematic reviews, we did not seek to directly compare either CR interventions across reviews (e.g. exercise CR versus education for CHD) or to compare interventions across review populations (e.g. exercise CR for CHD versus exercise CR for HF). For this reason we have made no attempt to compare outcome results across trials using indirect network meta-analysis methods.

Reaching conclusions

We will base our conclusions only on findings from the quantitative or narrative synthesis of included reviews in this overview. Our 'Implications for research' section will suggest priorities for future research and outline what the remaining uncertainties are in the area.

Acknowledgements

We are very grateful to Nicole Martin of the Cochrane Heart Group, London, for her help in developing the search strategy for this overview.

Appendices

Appendix 1. Appendix 1. Search strategy: The Cochrane Library

#1 cardiac near/4 rehab*

#2 cardiac near/4 exercise*

#1 OR #2

[Limited to Cochrane Database of Systematic Reviews]

Contributions of authors

Both authors contributed to the development of the review proposal, and the development and writing of the protocol.

Declarations of interest

RST was a co-author on five of the included systematic reviews.

Sources of support

Internal sources

  • University of Exeter Medical School, UK.

    LA and RST were core-funded by the University of Exeter Medical School

External sources

  • No sources of support supplied

Ancillary