Literature DB >> 31245012

Exercise-based cardiac rehabilitation for stable angina: systematic review and meta-analysis.

Linda Long1, Lindsey Anderson2, Jingzhou He3, Manish Gandhi3, Alice Dewhirst4, Charlene Bridges5, Rod Taylor1.   

Abstract

Objective: A systematic review was undertaken to assess the effects of exercise-based cardiac rehabilitation (CR) for patients with stable angina.
Methods: Databases (Cochrane Central Register of Controlled Trials, MEDLINE, Embase and CINAHL) were searched up to October 2017, without language restriction. Randomised trials comparing CR programmes with no exercise control in adults with stable angina were included. Where possible, study outcomes were pooled using meta-analysis. Grading of Recommendations Assessment, Development and Evaluation was used to assess the quality of evidence. The protocol was published on the Cochrane Database of Systematic Reviews.
Results: Seven studies (581 patients), with a median of 12-month follow-up, were included. The effect of exercise-based CR on all-cause mortality (risk ratio (RR) 1.01, 95 % CI: 0.18 to 5.67), acute myocardial infarction (RR 0.33, 95% CI: 0.07 to 1.63) and cardiovascular-related hospital admissions (RR 0.14, 95% CI: 0.02 to 1.1) relative to control were uncertain. We found low-quality evidence that exercise-based CR results in a moderate improvement in exercise capacity (standard mean difference 0.45, 95% CI: 0.20 to 0.70). There was limited and very low-quality evidence for the effect of exercise-based CR on health-related quality of life (HRQoL), adverse events and costs. No data were identified on cost-effectiveness or return to work. Conclusions: Exercise-based CR may improve the short-term exercise capacity of patients with stable angina pectoris. Well-designed randomised controlled trials are needed to definitely determine the impact of CR on outcomes including mortality, morbidity, HRQoL, and costs in the population of patients with stable angina receiving contemporary medical therapy.

Entities:  

Keywords:  cardiac rehabilitation; exercise; stable angina; systematic review

Year:  2019        PMID: 31245012      PMCID: PMC6560669          DOI: 10.1136/openhrt-2018-000989

Source DB:  PubMed          Journal:  Open Heart        ISSN: 2053-3624


Cardiac rehabilitation (CR) is recognised as integral to the comprehensive care of patients with coronary heart disease. CR is a process by which patients, in partnership with health professionals, are encouraged and supported to achieve and maintain optimal physical health, with exercise training at the centre of rehabilitation provision for CR. There is an absence of evidence and consequently inconsistency in guideline and policy recommendations for the use of CR programme for patients with stable angina. American College of Cardiology/American Heart Association and European Society of Cardiology guidelines recommend CR for patients with cardiac disease, including patients with stable angina. The 2017 British Association for Cardiovascular Prevention and Rehabilitation guidelines recommend CR for people with established forms of cardiovascular disease, including stable angina. However, the National Institute for Health and Care Excellence do not recommend CR in their clinical guidelines for the management of stable angina. This systematic review assesses the impact of CR for people with stable angina, defined in this review as chest pain and associated symptoms precipitated by activity (eg, running, walking) with minimal or non-existent symptoms at rest. The review finds exercise-based CR may improve the short-term exercise capacity of people with stable angina pectoris, based on low-quality evidence. The review finds insufficient evidence to determine effectiveness of exercise-based CR on clinical relevant outcomes or quality of life. The impact of exercise-based CR for adults with stable angina is uncertain due to insufficient evidence, with the quality of the evidence graded as low to very low. However, it may be associated with a moderate increase in exercise capacity compared with no exercise control. Well-designed randomised controlled trials are required to definitively assess the impact of adding CR to contemporary usual care in terms of mortality, morbidity, health-related quality of life, and costs.

Introduction

With increasing numbers of patients living longer with symptomatic coronary heart disease (CHD), the effectiveness and accessibility of health services for patients with CHD have never been more important. Cardiac rehabilitation (CR) is recognised as integral to the comprehensive care of patients with CHD.1 CR is a process by which patients, in partnership with health professionals, are encouraged and supported to achieve and maintain optimal physical health.2 While physical exercise training is at the centre of rehabilitation provision for CR, it is now accepted that programmes should be comprehensive in nature and also include education and psychological care, as well as focus on health and life-style behaviour change and psychosocial well-being.3 Stable angina is a form of chronic heart disease associated with ill health and increased death rates and is defined in this review as chest pain and associated symptoms precipitated by activity (eg, running, walking) with minimal or non-existent symptoms at rest. It was estimated that in 2013 over 1.3 million people in the UK had angina4 and it was thought to affect approximately 112 million people, or 1.6% of the population worldwide.5 Although clinical guidelines consistently recommend referral for CR for post-myocardial infarction (MI) and patients with heart failure (HF), advice for patients with stable angina is less clear. The American College of Cardiology/American Heart Association give a Class I recommendation that medically supervised CR programmes and physician-directed, home-based programme are offered to at-risk patients with stable CHD including those with stable angina, at first diagnosis.6 Similarly, the European Society of Cardiology recommends that people with stable CHD, including stable angina, should undergo ‘moderate-to-vigorous intensity aerobic exercise training ≥3 times a week and for 30 min per session’.7 However, National Health and Care Excellence (NICE) guideline for the management of stable angina (CG126) states that there is ‘no evidence to suggest that CR is clinically or cost-effective for managing stable angina’.8 To inform current practice and policy, we therefore sought to undertake a systematic review and meta-analysis of randomised controlled trials (RCTs) to assess the effects of exercise-based CR versus usual care on mortality, morbidity, hospital admissions, exercise capacity, health-related quality of life (HRQoL), adverse events and return to work for adults with stable angina.

Methods

We conducted and reported this systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and the Cochrane Handbook for Interventional Reviews.9 The protocol was published on the Cochrane Database of Systematic Reviews.10

Searches

We adapted the search strategy based on the Cochrane systematic review of exercise-based CR for CHD.11 We searched databases using a strategy combining selected Medical Subject HeadingsMeSH terms and free-text terms relating to exercise-based rehabilitation and stable angina, with filters applied to limit to RCTs. Electronic searches of the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and CINAHL plus others (see online supplementary document A) were performed. Databases were searched up to September 2016 with no language or other restrictions, and then updated with a further search up to October 2017. Trial registers (www.who.int/ictrp/en and clinicaltrials.gov) were also checked, in addition to reference lists of all eligible studies and other published systematic reviews.

Study selection

We included randomised trials (individual or cluster) directly comparing CR programmes with a no exercise control or usual care comparison. The study population included adults with stable or exertional angina (effort-induced chest discomfort), who were being treated with medical anti-anginal therapy and who may have had a MI, coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI). We excluded patients in the immediate period following such an event that is, within 3 months of previous MI, CABG or PCI. We also excluded patients with unstable angina (pain at rest) and those with refractory angina for whom revascularisation was planned. Studies with one or more of the following outcome measures with ≥6 month-follow-up were included: mortality (cardiac and overall); morbidity (reinfarction, revascularisation or cardiac-related hospitalisation); exercise capacity; HRQoL, adverse events (withdrawal from the trial or exercise programme); return to work. Selection of studies involved the initial screening of titles and abstracts, followed by an assessment of the full-text reports of all potentially relevant trials. Two authors (AD and LA) independently assessed trials for inclusion and where there was a disagreement, the opinion of a third author (RST, GH or MG) was sought.

Data extraction and risk of bias assessment

The following information was extracted: study design, participants (baselinecharacteristics), details of the intervention (including type, frequency, duration and intensity of exercise training and nature of co-interventions), length of follow-up and outcome results. We assessed study risk of bias using the Cochrane standard criteria9 (random sequence generation and allocation concealment, dropouts and withdrawals, outcome blinding, and selective reporting) and two further items deemed relevant to this review (balance of groups at baseline and if the study groups received comparable care (apart from the exercise component of the intervention)). These criteria, agreed on in advance by the review authors, have not been validated but have been used to assess quality in previous CR reviews11–15 Data extraction and risk of bias assessment were carried out independently by three authors (LL, JH and AD). Any disagreements were resolved by consensus and decisions were independently checked by a third author (RST). Where necessary, authors of included studies were contacted for further information (eg, when a study was identified as abstract only).

Data analysis

Data were analysed in accordance with the Cochrane Handbook.9 For dichotomous variables, relative risks (RRs) and 95% CIs were calculated for each outcome, and for continuous variables, mean differences (MDs) and 95% CIs were calculated. Given the variety of outcome measures reported for exercise capacity, to allow us to pool findings across studies, between-group results for each study were expressed as a standard MD (SMD). Where differences between groups for each individual trial were not reported, we calculated p values for the differences. We explored heterogeneity among the included studies qualitatively (by comparing the study characteristics) and quantitatively (using the χ2 test of heterogeneity and I2 statistic). Where appropriate, an overall estimate of treatment effect was obtained by combining the results from included studies for each outcome. We employed a random-effects model where there was formal evidence of statistical heterogeneity (ie, χ2 test p value<0.10 and I2 statistic of 50%–90%). For outcomes with lower levels of statistical heterogeneity, we applied both fixed and random effects models, reporting fixed-effects results unless there was a difference in statistical inference, where we reported the most conservative random-effects model. We sought to explore small-study bias and the potential for publication bias using funnel plot and the Egger test16 Analyses were undertake using Review Manager Software V.5.3 (Nordic Cochrane Group, Copenhagen, Denmark).

Summary of findings table

Two reviewers (LL and RST) independently employed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach17 to interpret result findings. We used the five GRADE considerations (study limitations, consistency of effect, imprecision, indirectness and publication bias) to assess the quality of a body of evidence from studies that contributed data to the meta-analyses and narrative summaries for the pre-specified outcomes. Any discrepancies in judgements were resolved through discussion. One reviewer (LL) used GRADEpro GDT 2015 to import data from Review Manager to create a ‘Summary of findings’ table using the following pre-specified outcomes: all-cause mortality; MI; all-cause hospital admissions; HRQoL, return to work and exercise capacity.

Results

Figure 1 summarises the screening process resulting in eight publications across seven RCTs included in the review.
Figure 1

Summary of study selection process. RCT, randomised controlled trials.

Summary of study selection process. RCT, randomised controlled trials.

Characteristics of included studies

The seven RCTs included a total of 581 patients with stable angina. A summary of study characteristics is shown in tables 1 and 2. Summary of individual studies AMI, acute myocardial infarction; CABG, coronary artery bypass graft; CCS, Canadian Cardiovascular Society; HRQoL, health-related quality of life; MI, myocardial infarction; PCI, percutaneous coronary intervention. Summary of study characteristics 70%–75% of maximal heart rate ‘Moderate’ intensity PCI, percutaneous coronary intervention.

Risk of bias

Overall risk of bias was judged to be poor, most studies being insufficiently reported to fully assess their potential risk of bias (see figure 2). The reporting of details tended to be poorer in studies published prior to 2000.18–20 Details of selection bias (random allocation sequence generation and concealment) and reporting bias were particularly poorly reported. Only two studies stated they took measures to blind outcome assessment.18 21 Loss to follow-up or dropout as well as whether groups received the same co-interventions appeared to vary considerably across studies. Where reported, losses to follow-up and drop-out were relatively high, ranging from 15% to 58% across studies. The majority of trials were judged to be of low risk of bias in terms of the risk associated with groups being unbalanced at baseline.
Figure 2

Risk of bias summary: review authors' judgements about each risk of bias item for each included study. + (green), low risk of bias; ? (yellow), unclear risk of bias; − (red), high risk of bias.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study. + (green), low risk of bias; ? (yellow), unclear risk of bias; − (red), high risk of bias.

Impact of CR on outcomes

Mortality and morbidity

Three studies19 20 22 (195 participants) reported a total of four all-cause deaths with a pooled RR of 1.01 (95% CI: 0.18 to 5.67, I2=0%, fixed effects). We are uncertain if CR has little or no effect on all-cause mortality due to very low-quality evidence (Summary of findings table 3). One study (Schuler 1992)20 reported cardiovascular-related mortality in two participants in the CR group and none in the control.
Table 3

Summary of findings table

OutcomesAnticipated absolute effects* (95% CI)Relative effect(95% CI)No of participants(studies)Quality of the evidence(GRADE)
Risk with usual careRisk with exercise-based CR
All-cause mortalityFollow-up: 12 months20 per 100021 per 1000(4 to 116)RR 1.01(0.18 to 5.67)195(3 RCTs)⨁◯◯◯Very low*†‡
AMIFollow-up: 12 months39 per 100013 per 1000(3 to 64)RR 0.33(0.07 to 1.63)254(3 RCTs)⨁◯◯◯Very low†‡§
Exercise capacity assessed using a variety of outcomes including VO2 max and duration of exerciseFollow-up: range 6 months to 12 monthsThe mean exercise capacity in the intervention groups was 0.45 SD higher(0.2 higher to 0.7 higher)267(5 RCTs)⨁⨁◯◯Low¶**
Cardiovascular hospital admissions assessed with: Combined clinical endpoint (cardiac death, stroke, CABG, PCI, AMI, worsening angina with objective evidence resulting in hospitalisation)Follow-up: 12 monthsRisk with usual care 140 per 1000Risk with exercise-based CR 20 per 1000 (2–154)RR 0.14(0.02 to 1.1)101(1 RCT)⨁◯◯◯Very low†††‡‡
HRQoL assessed with: Seattle angina questionnaire and The MacNew questionnaireFollow-up: range 6 weeks to 6 monthsOne study showed improvement in emotional score at 6 week follow-up, and benefits in angina frequency and social HRQoL score at 6 months follow-upNot estimable94(1 RCT)⨁◯◯◯VERY LOW§§‡‡
Return to workNo studies were found that looked at return to work.
Adverse eventsFollow-up: 12 monthsFor example, skeletomuscular injuryOnly one study looked at adverse events and reported that there were no adverse events during the exercise-based CR.Not estimable101(1 RCTs)⨁◯◯◯Very low †††‡‡

* The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI)

*Some concerns with random sequence generation, allocation concealment, blinding of outcome assessment and selective reporting; bias likely, therefore quality of evidence downgraded by one level.

†Some concern with applicability to review question as participants in all studies were limited to middle-aged men, therefore quality of evidence downgraded by one level.

‡Imprecise due to small number of participants (less than 300) and CIs including potential for important harm or benefit as 95% CI crosses RR of 0.75 and 1.25, therefore quality of evidence downgraded by two levels.

§Some concern with random sequence generation, allocation concealment, blinding of outcome assessment, high loss to follow-up, selective reporting and unbalanced groups at baseline; serious bias likely, therefore quality of evidence downgraded by two levels.

¶Some concern with random sequence generation, allocation concealment, blinding of outcome assessment, selective reporting and unbalanced groups at baseline; bias likely, therefore quality of evidence downgraded by one level.

**Imprecise due to small number of participants (less than 300), therefore quality of evidence downgraded by one level.

††Some concerns with random sequence generation, allocation concealment and selective reporting; bias likely, therefore quality of evidence downgraded by one level.

‡‡Imprecise due to very small number of participants therefore quality of evidence downgraded by two levels.

§§Some concerns with blinding of outcome assessment, selective reporting and groups not receiving comparable care; bias likely, therefore quality of evidence downgraded by one level.

AMI, acute myocardial infarction; CABG, coronary artery bypass graft; CR, cardiac rehabilitation; GRADE, Grading of Recommendations Assessment, Development and Evaluation; HRQoL, health-related quality of life; PCI, percutaneous coronary intervention; RCT, randomised controlled trial.

Summary of findings table * The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI) *Some concerns with random sequence generation, allocation concealment, blinding of outcome assessment and selective reporting; bias likely, therefore quality of evidence downgraded by one level. †Some concern with applicability to review question as participants in all studies were limited to middle-aged men, therefore quality of evidence downgraded by one level. ‡Imprecise due to small number of participants (less than 300) and CIs including potential for important harm or benefit as 95% CI crosses RR of 0.75 and 1.25, therefore quality of evidence downgraded by two levels. §Some concern with random sequence generation, allocation concealment, blinding of outcome assessment, high loss to follow-up, selective reporting and unbalanced groups at baseline; serious bias likely, therefore quality of evidence downgraded by two levels. ¶Some concern with random sequence generation, allocation concealment, blinding of outcome assessment, selective reporting and unbalanced groups at baseline; bias likely, therefore quality of evidence downgraded by one level. **Imprecise due to small number of participants (less than 300), therefore quality of evidence downgraded by one level. ††Some concerns with random sequence generation, allocation concealment and selective reporting; bias likely, therefore quality of evidence downgraded by one level. ‡‡Imprecise due to very small number of participants therefore quality of evidence downgraded by two levels. §§Some concerns with blinding of outcome assessment, selective reporting and groups not receiving comparable care; bias likely, therefore quality of evidence downgraded by one level. AMI, acute myocardial infarction; CABG, coronary artery bypass graft; CR, cardiac rehabilitation; GRADE, Grading of Recommendations Assessment, Development and Evaluation; HRQoL, health-related quality of life; PCI, percutaneous coronary intervention; RCT, randomised controlled trial.

Morbidity

Three studies19–21 (254 participants) reported on the incidence of MI with a total of six events. There was a pooled RR for risk of MI of 0.33 (95% CI: 0.07 to 1.63, I2=0%, fixed effects). We are uncertain if CR has little or no effect on the incidence of MI due to very low-quality evidence (Summary of findings table 3). Three studies20–22 (256 participants) reported on the incidence of revascularisations with a total of 28 events. In total, six revascularisations were reported among the CR groups in the three studies, and 22 in the control groups, with a pooled RR for risk of revascularisations of 0.27 (95% CI: 0.11 to 0.64, I2=0%, fixed effects). We are uncertain if CR has little or no effect on the incidence of revascularisations due to very low-quality evidence (Summary of findings table 3). One study21 (101 participants) reported that one CR participant and seven control participants experienced cardiovascular-related hospital admissions (RR 0.14, 95% CI: 0.02 to 1.10). We are uncertain if CR has little or no effect on the incidence of cardiovascular-related hospital admissions due to very low-quality evidence (Summary of findings table 3). None of the included studies reported all-cause hospital admissions.

Exercise capacity

Five studies18–22 (267 participants) reported exercise capacity with a range of validated measures (peak oxygen uptake and exercise duration) (figure 3). CR may result in a moderate improvement in exercise capacity with CR compared with control in the short term (6–12 months follow-up) (SMD 0.45, 95% CI: 0.20 to 0.70; I2=16%, fixed effects) (figure 3) based on low-quality evidence (Summary of findings table 3). Studies varied in degree of losses to follow-up which ranged from 0%20 to 29%21 in the intervention arm.
Figure 3

Exercise capacity with exercise-based CR versus no exercise for stable angina. CR, cardiac rehabilitation.

Exercise capacity with exercise-based CR versus no exercise for stable angina. CR, cardiac rehabilitation.

HRQoL

One study23 (94 participants) reported HRQoL using validated disease-specific instruments (Seattle angina questionnaire and MacNew questionnaire). Compared with control, improvements with CR at the 6-week follow-up were seen in emotional score (p=0.04) and angina frequency (p=0.002). Benefits in favour of CR in angina frequency (P=0.02) and social HRQoL score (p=0.02) were also observed at the 6-month follow-up. We are uncertain of the effect of CR on HRQoL due to very low-quality evidence (Summary of findings table 3).

Severity of angina

One study22 (42 participants) reported a reduction in mean New York Heart Association (NYHA) score from baseline to 1-year follow-up (2.6–1.4, p<0.0001) with CR and an increase in mean NYHA in control (2.3–2.9, p≤0.004). Another study21 (101 participants) reported an improvement in angina severity assessed by mean Canadian Cardiovascular Society score in both CR (1.5–0.4, p<0.001) and control (1.7–0.7, p<0.001). We assessed the evidence as very low‐quality using GRADE because of concerns about risk of bias (random sequence generation, allocation concealment, blinding of outcome assessment, selective reporting, high losses to follow‐up and unbalanced groups at baseline), concerns about applicability to review question (participants in all studies were limited to middle‐aged men) and concerns about imprecision (small number of participants). Data could not be pooled in a meta‐analysis because of scales used to report outcome measures (ie, NYHA is categorical while CCS is continuous).

Adverse events

Adverse events were only reported in one study21 (101 participants). The authors reported ‘no adverse events’ during the exercise training programme in the CR group (summary of findings in table 3).

Healthcare costs

One study21 (101 participants) reported a difference in mean participant healthcare costs in favour of CR (CR: US$3708 vs control: US$6086, p<0.0001). These costs included hospitalisations, repeat vascularisations, any other cardiovascular events plus the costs of the provision of the CR exercise training programme. We assessed this evidence as very low‐quality using GRADE because of concerns about risk of bias (random sequence generation, allocation concealment, high losses to follow‐up and selective reporting), concerns about applicability to review question (participants in all studies were limited to middle‐aged men) and concerns about imprecision (small number of participants). We are uncertain of the effect of CR on healthcare costs due to very low-quality evidence.

Return to work

None of the included studies reported on return to work (summary of findings in table 3)

Small study bias

There were insufficient (<10 RCTs) studies to assess small study bias using Funnel plot or Egger test.

Discussion

This systematic review identified seven RCTs in 581 patients with a confirmed diagnosis of stable angina that compared exercise-based CR with a no exercise control. Meta-analysis and GRADE analysis showed there may be an improvement in exercise capacity following CR compared with control in the short term (up to 12 months follow-up, low-quality evidence). However, there was insufficient evidence to be able to definitely assess impact of CR on mortality, morbidity, or HRQoL. The limited evidence base for CR for stable angina identified by this review is in contrast to that reported for post-MI, following coronary revascularisation, and in patients with HF. A Cochrane meta-analysis of exercise-based CR for CHD identified 63 RCTs in 14 486 patients, the majority following MI or coronary revascularisation. Compared with no-exercise control, the authors reported that CR reduced the risk of cardiovascular mortality (risk ratio (RR) 0.74, 95% CI 0.64 to 0.86 and hospital admission (RR 0.82, 95% CI 0.70 to 0.96) and improved HRQoL.11 A systematic review and meta-analysis comparing the effects of home-based and supervised centre-based CR found similar benefits in terms of clinical and HRQoL outcomes at equivalent cost for patients with HF and following MI and revascularisation.24 The precise mechanisms by which CR may improve mortality in people with CHD has not been fully elucidated. Exercise training has been shown to have direct benefits on the heart and coronary vasculature, including autonomic tone, endothelial function, myocardial oxygen demand, coagulation and clotting factors, inflammatory markers, and the development of coronary collateral vessels.25–27 However, it has been suggested that approximately half of the 28% reduction in cardiac mortality in people with CHD may also be mediated via the indirect effects of exercise through improvements in the risk factors for atherosclerotic disease (ie, smoking, blood pressure and total cholesterol).28 A recent review that focused on contemporary exercise-based CR found no improvement in all-cause mortality and potential benefit on hospital admissions.29 A recent Cochrane review from 201930 of exercise-based CR identified 44 RCTs that included 5783 people with HF. The findings show important benefits of exercise-based rehabilitation that include a probable reduction in the risk of overall hospital admissions in the short term (RR: 0.7, 95% CI 0.6 to 0.83), as well as the potential for reduction in HF admissions (RR: 0.59 95% CI 0.42 to 0.84) compared with usual care control. The effect of exercise-based rehabilitation on HRQoL is uncertain due to very low-quality evidence. Exercise-based rehabilitation may make little or no difference in all-cause mortality in trials with follow-up less than 12 months.

Strengths and limitations

We believe this to be the first systematic review and meta-analysis to specifically assess the impact of CR in patients with stable angina. Strengths of this review include extensive literature searches, consideration of RCTs, application of Cochrane review methodology and consideration of a wide range of outcomes. However, a major limitation was the small number of RCTs and patients included in the studies. It was therefore not possible to assess potential small study effects and publication bias. Trials generally recruited primarily younger middle-aged men,19–22 limiting external generalisability. A number of the trials were in patient populations with poorly defined baseline characteristics in terms of their angiographic coronary disease and left ventricular ejection fraction and were not receiving contemporary medical therapy (ie, antiplatelet, antianginal and revascularisation therapies).

Implications for clinical practice and future research

It is estimated that stable angina is prevalent in over 1.3 million people in the UK,4 and in approximately 112 million people, or 1.6% of the population worldwide.5 The findings of this review support NICE clinical guidance that there is currently insufficient evidence to conclude whether CR is clinically effective or cost-effective for stable angina. Adequately powered, high-quality, multi-centre randomised trials of exercise-based CR in patients with stable angina receiving contemporary medical care are required. Such trials should seek to compare CR to contemporary usual care, assessing outcomes that include symptom burden with validated angina questionnaires and HRQoL measures, report clinical events including hospital admissions, all-cause mortality, and, costs and cost-effectiveness.

Conclusions

The results of this systematic review and meta-analysis show that exercise-based CR may improve short-term exercise capacity in patients with stable angina pectoris. There is insufficient evidence to draw conclusions for any other outcome. Given the limited body of available evidence, well-designed RCTs in a contemporary patient population are required to definitely assess the impact of adding CR to usual care in terms of mortality, morbidity, HRQoL and costs.
Table 1

Summary of individual studies

StudyParticipants (number and % men)Intervention, comparator and settingExercise prescripti0mOutcomesFollow-upCountry/setting
Devi et al 20142394 stable angina pectoris; 74% menHome-based online web-based interventionDose: Individualised daily exercise (most commonly walking)Length of session: Not reportedFrequency: DailyIntensity: ModerateTotal duration: 6 weeksHRQoL and anxiety and depression6 monthsUK, single centre
Hambrecht et al 200421101 classes I to III angina pectoris;100% menHome-based aerobic training (bicycle ergometer)Dose: 48×7×20 minLength of session: 20 minFrequency: DailyIntensity: Not reportedTotal duration: 12 monthsAngina symptoms (CCS), exercise capacity, revascularisations, MI, cost- effectiveness, combined clinical endpoint (death cardiac, stroke, CABG, PCI, AMI, worsening angina with objective evidence resulting in hospitalisation)12 monthsGermany, single centre
Jiang et al 2007167 first hospitalised with angina pectoris or MI;71.2% menHospital-based patient/family education and home-based rehabilitation careDose: Not reportedLength of session: Not reportedFrequency: Not reportedIntensity: Not reportedTotal duration: 12 weeksNone relevant to this review6 monthsChina, single centre
Manchanda et al 20002242 chronic stable angina pectoris and coronary artery disease (CAD); 100% menHome-based yoga lifestyle intervention programmeDose: 48×7×90 minLength of session: 90 minFrequency: DailyIntensity: ModerateTotal duration: 12 monthsAll-cause mortality, severity of angina, revascularisation, exercise capacity12 monthsIndia, single centre
Raffo et al 19801824 stable angina pectoris; 88% menHospital-based aerobic training (Canadian Air Force Programme)Dose: 24×7×11Length of session: 11–12 min (daily)Frequency: Daily (at home)Intensity: Training started at lowest physical capacity level, and progressed by increasing this level according to their age and sex.Total duration: 6 monthsExercise capacity6 monthsCountry not reported, single centre
Schuler et al 199220113 stable angina pectoris; 100% menHome-based aerobic training (bicycle ergometer)Dose: 48×7×30 min (daily exercise) plus 48×2×60 min (weekly exercise)Length of session: 30 min minimumFrequency: DailyIntensity: 75% maximal heart rate during symptom-limited exerciseTotal duration: 12 monthsAll-cause mortality, MI, revascularisations, exercise capacity, adverse events12 monthsGermany, single centre
Todd et al 19911940 chronic stable angina >6 months durationHome-based aerobic training (Canadian Air Force Programme)Dose: 48×7×11Length of session: 11 minFrequency: DailyIntensity: Increasing intensity with no limit on maximum exercise levelTotal duration: 12 monthsAll-cause mortality, MI, exercise capacity12 monthsUK, single centre

AMI, acute myocardial infarction; CABG, coronary artery bypass graft; CCS, Canadian Cardiovascular Society; HRQoL, health-related quality of life; MI, myocardial infarction; PCI, percutaneous coronary intervention.

Table 2

Summary of study characteristics

Number of studies (%) or median (range)
Study characteristics
 Publication year
  1980–19993
  2000–20093
  2010 onwards1
 Study location
  Europe5
  Australasia2
  Single centre7
  Sample size126 (24–167)
  Duration of follow-up9.4 months (6–12)
 Comparator
  Usual medical care6
  PCI1
Population characteristics
 Sex
  Males only4
  Both males and females3
 Age (years)56.6 (50–66.2)
Intervention characteristics
  Intervention type
  Exercise-only programme4
  Comprehensive programme3
 Duration of intervention (months)57.5 (1.5–12)
 Nature of intervention
  Aerobic only7
  Aerobic and resistance0
 Dose of intervention
  Duration57.5 months (1.5–12)
  Frequency1–7 sessions/week
  Length11–90 min/session
  Intensity

70%–75% of maximal heart rate

‘Moderate’ intensity

 Setting
  Centre-based only1
  Combination of centre- and home-based3
  Home-based only2

PCI, percutaneous coronary intervention.

  23 in total

1.  Retardation of coronary atherosclerosis with yoga lifestyle intervention.

Authors:  S C Manchanda; R Narang; K S Reddy; U Sachdeva; D Prabhakaran; S Dharmanand; M Rajani; R Bijlani
Journal:  J Assoc Physicians India       Date:  2000-07

2.  2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology.

Authors:  Gilles Montalescot; Udo Sechtem; Stephan Achenbach; Felicita Andreotti; Chris Arden; Andrzej Budaj; Raffaele Bugiardini; Filippo Crea; Thomas Cuisset; Carlo Di Mario; J Rafael Ferreira; Bernard J Gersh; Anselm K Gitt; Jean-Sebastien Hulot; Nikolaus Marx; Lionel H Opie; Matthias Pfisterer; Eva Prescott; Frank Ruschitzka; Manel Sabaté; Roxy Senior; David Paul Taggart; Ernst E van der Wall; Christiaan J M Vrints; Jose Luis Zamorano; Stephan Achenbach; Helmut Baumgartner; Jeroen J Bax; Héctor Bueno; Veronica Dean; Christi Deaton; Cetin Erol; Robert Fagard; Roberto Ferrari; David Hasdai; Arno W Hoes; Paulus Kirchhof; Juhani Knuuti; Philippe Kolh; Patrizio Lancellotti; Ales Linhart; Petros Nihoyannopoulos; Massimo F Piepoli; Piotr Ponikowski; Per Anton Sirnes; Juan Luis Tamargo; Michal Tendera; Adam Torbicki; William Wijns; Stephan Windecker; Juhani Knuuti; Marco Valgimigli; Héctor Bueno; Marc J Claeys; Norbert Donner-Banzhoff; Cetin Erol; Herbert Frank; Christian Funck-Brentano; Oliver Gaemperli; José R Gonzalez-Juanatey; Michalis Hamilos; David Hasdai; Steen Husted; Stefan K James; Kari Kervinen; Philippe Kolh; Steen Dalby Kristensen; Patrizio Lancellotti; Aldo Pietro Maggioni; Massimo F Piepoli; Axel R Pries; Francesco Romeo; Lars Rydén; Maarten L Simoons; Per Anton Sirnes; Ph Gabriel Steg; Adam Timmis; William Wijns; Stephan Windecker; Aylin Yildirir; Jose Luis Zamorano
Journal:  Eur Heart J       Date:  2013-08-30       Impact factor: 29.983

3.  2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons.

Authors:  Stephan D Fihn; Julius M Gardin; Jonathan Abrams; Kathleen Berra; James C Blankenship; Apostolos P Dallas; Pamela S Douglas; Joanne M Foody; Thomas C Gerber; Alan L Hinderliter; Spencer B King; Paul D Kligfield; Harlan M Krumholz; Raymond Y K Kwong; Michael J Lim; Jane A Linderbaum; Michael J Mack; Mark A Munger; Richard L Prager; Joseph F Sabik; Leslee J Shaw; Joanna D Sikkema; Craig R Smith; Sidney C Smith; John A Spertus; Sankey V Williams
Journal:  J Am Coll Cardiol       Date:  2012-11-19       Impact factor: 24.094

4.  Effect of exercise on coronary endothelial function in patients with coronary artery disease.

Authors:  R Hambrecht; A Wolf; S Gielen; A Linke; J Hofer; S Erbs; N Schoene; G Schuler
Journal:  N Engl J Med       Date:  2000-02-17       Impact factor: 91.245

5.  Regular physical exercise and low-fat diet. Effects on progression of coronary artery disease.

Authors:  G Schuler; R Hambrecht; G Schlierf; J Niebauer; K Hauer; J Neumann; E Hoberg; A Drinkmann; F Bacher; M Grunze
Journal:  Circulation       Date:  1992-07       Impact factor: 29.690

6.  Mortality reductions in patients receiving exercise-based cardiac rehabilitation: how much can be attributed to cardiovascular risk factor improvements?

Authors:  Rod S Taylor; Belgin Unal; Julia A Critchley; Simon Capewell
Journal:  Eur J Cardiovasc Prev Rehabil       Date:  2006-06

7.  Percutaneous coronary angioplasty compared with exercise training in patients with stable coronary artery disease: a randomized trial.

Authors:  Rainer Hambrecht; Claudia Walther; Sven Möbius-Winkler; Stephan Gielen; Axel Linke; Katrin Conradi; Sandra Erbs; Regine Kluge; Kai Kendziorra; Osama Sabri; Peter Sick; Gerhard Schuler
Journal:  Circulation       Date:  2004-03-08       Impact factor: 29.690

Review 8.  Home-based versus centre-based cardiac rehabilitation.

Authors:  Rod S Taylor; Hayes Dalal; Kate Jolly; Tiffany Moxham; Anna Zawada
Journal:  Cochrane Database Syst Rev       Date:  2010-01-20

9.  Effects of daily high-intensity exercise on myocardial perfusion in angina pectoris.

Authors:  I C Todd; M S Bradnam; M B Cooke; D Ballantyne
Journal:  Am J Cardiol       Date:  1991-12-15       Impact factor: 2.778

10.  Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010.

Authors:  Theo Vos; Abraham D Flaxman; Mohsen Naghavi; Rafael Lozano; Catherine Michaud; Majid Ezzati; Kenji Shibuya; Joshua A Salomon; Safa Abdalla; Victor Aboyans; Jerry Abraham; Ilana Ackerman; Rakesh Aggarwal; Stephanie Y Ahn; Mohammed K Ali; Miriam Alvarado; H Ross Anderson; Laurie M Anderson; Kathryn G Andrews; Charles Atkinson; Larry M Baddour; Adil N Bahalim; Suzanne Barker-Collo; Lope H Barrero; David H Bartels; Maria-Gloria Basáñez; Amanda Baxter; Michelle L Bell; Emelia J Benjamin; Derrick Bennett; Eduardo Bernabé; Kavi Bhalla; Bishal Bhandari; Boris Bikbov; Aref Bin Abdulhak; Gretchen Birbeck; James A Black; Hannah Blencowe; Jed D Blore; Fiona Blyth; Ian Bolliger; Audrey Bonaventure; Soufiane Boufous; Rupert Bourne; Michel Boussinesq; Tasanee Braithwaite; Carol Brayne; Lisa Bridgett; Simon Brooker; Peter Brooks; Traolach S Brugha; Claire Bryan-Hancock; Chiara Bucello; Rachelle Buchbinder; Geoffrey Buckle; Christine M Budke; Michael Burch; Peter Burney; Roy Burstein; Bianca Calabria; Benjamin Campbell; Charles E Canter; Hélène Carabin; Jonathan Carapetis; Loreto Carmona; Claudia Cella; Fiona Charlson; Honglei Chen; Andrew Tai-Ann Cheng; David Chou; Sumeet S Chugh; Luc E Coffeng; Steven D Colan; Samantha Colquhoun; K Ellicott Colson; John Condon; Myles D Connor; Leslie T Cooper; Matthew Corriere; Monica Cortinovis; Karen Courville de Vaccaro; William Couser; Benjamin C Cowie; Michael H Criqui; Marita Cross; Kaustubh C Dabhadkar; Manu Dahiya; Nabila Dahodwala; James Damsere-Derry; Goodarz Danaei; Adrian Davis; Diego De Leo; Louisa Degenhardt; Robert Dellavalle; Allyne Delossantos; Julie Denenberg; Sarah Derrett; Don C Des Jarlais; Samath D Dharmaratne; Mukesh Dherani; Cesar Diaz-Torne; Helen Dolk; E Ray Dorsey; Tim Driscoll; Herbert Duber; Beth Ebel; Karen Edmond; Alexis Elbaz; Suad Eltahir Ali; Holly Erskine; Patricia J Erwin; Patricia Espindola; Stalin E Ewoigbokhan; Farshad Farzadfar; Valery Feigin; David T Felson; Alize Ferrari; Cleusa P Ferri; Eric M Fèvre; Mariel M Finucane; Seth Flaxman; Louise Flood; Kyle Foreman; Mohammad H Forouzanfar; Francis Gerry R Fowkes; Richard Franklin; Marlene Fransen; Michael K Freeman; Belinda J Gabbe; Sherine E Gabriel; Emmanuela Gakidou; Hammad A Ganatra; Bianca Garcia; Flavio Gaspari; Richard F Gillum; Gerhard Gmel; Richard Gosselin; Rebecca Grainger; Justina Groeger; Francis Guillemin; David Gunnell; Ramyani Gupta; Juanita Haagsma; Holly Hagan; Yara A Halasa; Wayne Hall; Diana Haring; Josep Maria Haro; James E Harrison; Rasmus Havmoeller; Roderick J Hay; Hideki Higashi; Catherine Hill; Bruno Hoen; Howard Hoffman; Peter J Hotez; Damian Hoy; John J Huang; Sydney E Ibeanusi; Kathryn H Jacobsen; Spencer L James; Deborah Jarvis; Rashmi Jasrasaria; Sudha Jayaraman; Nicole Johns; Jost B Jonas; Ganesan Karthikeyan; Nicholas Kassebaum; Norito Kawakami; Andre Keren; Jon-Paul Khoo; Charles H King; Lisa Marie Knowlton; Olive Kobusingye; Adofo Koranteng; Rita Krishnamurthi; Ratilal Lalloo; Laura L Laslett; Tim Lathlean; Janet L Leasher; Yong Yi Lee; James Leigh; Stephen S Lim; Elizabeth Limb; John Kent Lin; Michael Lipnick; Steven E Lipshultz; Wei Liu; Maria Loane; Summer Lockett Ohno; Ronan Lyons; Jixiang Ma; Jacqueline Mabweijano; Michael F MacIntyre; Reza Malekzadeh; Leslie Mallinger; Sivabalan Manivannan; Wagner Marcenes; Lyn March; David J Margolis; Guy B Marks; Robin Marks; Akira Matsumori; Richard Matzopoulos; Bongani M Mayosi; John H McAnulty; Mary M McDermott; Neil McGill; John McGrath; Maria Elena Medina-Mora; Michele Meltzer; George A Mensah; Tony R Merriman; Ana-Claire Meyer; Valeria Miglioli; Matthew Miller; Ted R Miller; Philip B Mitchell; Ana Olga Mocumbi; Terrie E Moffitt; Ali A Mokdad; Lorenzo Monasta; Marcella Montico; Maziar Moradi-Lakeh; Andrew Moran; Lidia Morawska; Rintaro Mori; Michele E Murdoch; Michael K Mwaniki; Kovin Naidoo; M Nathan Nair; Luigi Naldi; K M Venkat Narayan; Paul K Nelson; Robert G Nelson; Michael C Nevitt; Charles R Newton; Sandra Nolte; Paul Norman; Rosana Norman; Martin O'Donnell; Simon O'Hanlon; Casey Olives; Saad B Omer; Katrina Ortblad; Richard Osborne; Doruk Ozgediz; Andrew Page; Bishnu Pahari; Jeyaraj Durai Pandian; Andrea Panozo Rivero; Scott B Patten; Neil Pearce; Rogelio Perez Padilla; Fernando Perez-Ruiz; Norberto Perico; Konrad Pesudovs; David Phillips; Michael R Phillips; Kelsey Pierce; Sébastien Pion; Guilherme V Polanczyk; Suzanne Polinder; C Arden Pope; Svetlana Popova; Esteban Porrini; Farshad Pourmalek; Martin Prince; Rachel L Pullan; Kapa D Ramaiah; Dharani Ranganathan; Homie Razavi; Mathilda Regan; Jürgen T Rehm; David B Rein; Guiseppe Remuzzi; Kathryn Richardson; Frederick P Rivara; Thomas Roberts; Carolyn Robinson; Felipe Rodriguez De Leòn; Luca Ronfani; Robin Room; Lisa C Rosenfeld; Lesley Rushton; Ralph L Sacco; Sukanta Saha; Uchechukwu Sampson; Lidia Sanchez-Riera; Ella Sanman; David C Schwebel; James Graham Scott; Maria Segui-Gomez; Saeid Shahraz; Donald S Shepard; Hwashin Shin; Rupak Shivakoti; David Singh; Gitanjali M Singh; Jasvinder A Singh; Jessica Singleton; David A Sleet; Karen Sliwa; Emma Smith; Jennifer L Smith; Nicolas J C Stapelberg; Andrew Steer; Timothy Steiner; Wilma A Stolk; Lars Jacob Stovner; Christopher Sudfeld; Sana Syed; Giorgio Tamburlini; Mohammad Tavakkoli; Hugh R Taylor; Jennifer A Taylor; William J Taylor; Bernadette Thomas; W Murray Thomson; George D Thurston; Imad M Tleyjeh; Marcello Tonelli; Jeffrey A Towbin; Thomas Truelsen; Miltiadis K Tsilimbaris; Clotilde Ubeda; Eduardo A Undurraga; Marieke J van der Werf; Jim van Os; Monica S Vavilala; N Venketasubramanian; Mengru Wang; Wenzhi Wang; Kerrianne Watt; David J Weatherall; Martin A Weinstock; Robert Weintraub; Marc G Weisskopf; Myrna M Weissman; Richard A White; Harvey Whiteford; Steven T Wiersma; James D Wilkinson; Hywel C Williams; Sean R M Williams; Emma Witt; Frederick Wolfe; Anthony D Woolf; Sarah Wulf; Pon-Hsiu Yeh; Anita K M Zaidi; Zhi-Jie Zheng; David Zonies; Alan D Lopez; Christopher J L Murray; Mohammad A AlMazroa; Ziad A Memish
Journal:  Lancet       Date:  2012-12-15       Impact factor: 79.321

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  6 in total

1.  Value of the Neutrophil to Lymphocyte Ratio and Platelet to Lymphocyte Ratio in Predicting CPET Performance in Patients with Stable CAD and Recent Elective PCI.

Authors:  Andrei Drugescu; Mihai Roca; Ioana Mădălina Zota; Alexandru-Dan Costache; Oana Irina Gavril; Radu Sebastian Gavril; Teodor Flaviu Vasilcu; Ovidiu Mitu; Irina Mihaela Esanu; Iulia-Cristina Roca; Cristina Mihaela Ghiciuc; Florin Mitu
Journal:  Medicina (Kaunas)       Date:  2022-06-16       Impact factor: 2.948

Review 2.  Molecular Mechanisms of Cardiac Remodeling and Regeneration in Physical Exercise.

Authors:  Dominik Schüttler; Sebastian Clauss; Ludwig T Weckbach; Stefan Brunner
Journal:  Cells       Date:  2019-09-23       Impact factor: 6.600

3.  Effectiveness of Intensive Cardiac Rehabilitation in High-Risk Patients with Cardiovascular Disease in Real-World Practice.

Authors:  Iwona Świątkiewicz; Salvatore Di Somma; Ludovica De Fazio; Valerio Mazzilli; Pam R Taub
Journal:  Nutrients       Date:  2021-10-29       Impact factor: 5.717

4.  MI-PACE Home-Based Cardiac Telerehabilitation Program for Heart Attack Survivors: Usability Study.

Authors:  Eric Y Ding; Nathaniel Erskine; Wim Stut; David D McManus; Amy Peterson; Ziyue Wang; Jorge Escobar Valle; Daniella Albuquerque; Alvaro Alonso; Naomi F Botkin; Quinn R Pack; David D McManus
Journal:  JMIR Hum Factors       Date:  2021-07-08

Review 5.  Effects of Supervised Cardiac Rehabilitation Programmes on Quality of Life among Myocardial Infarction Patients: A Systematic Review and Meta-Analysis.

Authors:  María Mansilla-Chacón; José L Gómez-Urquiza; María Begoña Martos-Cabrera; Luis Albendín-García; José L Romero-Béjar; Guillermo A Cañadas-De La Fuente; Nora Suleiman-Martos
Journal:  J Cardiovasc Dev Dis       Date:  2021-11-27

6.  Multicomponent Cardiac Rehabilitation and Cardiovascular Outcomes in Patients With Stable Angina: A Systematic Review and Meta-analysis.

Authors:  Farzane Saeidifard; Yanhui Wang; Jose R Medina-Inojosa; Ray W Squires; Hsu-Hang Huang; Randal J Thomas
Journal:  Mayo Clin Proc Innov Qual Outcomes       Date:  2021-07-24
  6 in total

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