Stable Angina

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Exercise-based cardiac rehabilitation for adults with stable angina

(Review)
Long L, Anderson L, Dewhirst AM, He J, Bridges C, Gandhi M, Taylor RS
Long L, Anderson L, Dewhirst AM, He J, Bridges C, Gandhi M, Taylor RS.

Exercise-based cardiac rehabilitation for adults with stable angina.
Cochrane Database of Systematic Reviews 2018, Issue 2. Art. No.: CD012786.
DOI: 10.1002/14651858.CD012786.pub2.
www.cochranelibrary.com
Exercise-based cardiac rehabilitation for adults with stable angina (Review)

Copyright © 2018 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews
TABLE OF CONTENTS
ABSTRACT..................................................................................................................................................................................................... 1
PLAIN LANGUAGE SUMMARY....................................................................................................................................................................... 2
SUMMARY OF FINDINGS.............................................................................................................................................................................. 3
BACKGROUND.............................................................................................................................................................................................. 6
OBJECTIVES.................................................................................................................................................................................................. 7
METHODS..................................................................................................................................................................................................... 7
RESULTS........................................................................................................................................................................................................ 10
Figure 1.................................................................................................................................................................................................. 11
Figure 2.................................................................................................................................................................................................. 12
Figure 3.................................................................................................................................................................................................. 13
DISCUSSION.................................................................................................................................................................................................. 15
AUTHORS' CONCLUSIONS........................................................................................................................................................................... 16
ACKNOWLEDGEMENTS................................................................................................................................................................................ 17
REFERENCES................................................................................................................................................................................................ 18
CHARACTERISTICS OF STUDIES.................................................................................................................................................................. 21
DATA AND ANALYSES.................................................................................................................................................................................... 36
Analysis 1.1. Comparison 1 Exercise versus no exercise for stable angina, Outcome 1 All-cause mortality.................................... 36
Analysis 1.2. Comparison 1 Exercise versus no exercise for stable angina, Outcome 2 Acute myocardial infarction (AMI)............. 37
Analysis 1.3. Comparison 1 Exercise versus no exercise for stable angina, Outcome 3 Revascularisation procedure (CABG or 37
PCI).........................................................................................................................................................................................................
Analysis 1.4. Comparison 1 Exercise versus no exercise for stable angina, Outcome 4 Exercise capacity....................................... 37
Analysis 1.5. Comparison 1 Exercise versus no exercise for stable angina, Outcome 5 Cardiovascular-related hospital 38
admissions.............................................................................................................................................................................................
APPENDICES................................................................................................................................................................................................. 38
CONTRIBUTIONS OF AUTHORS................................................................................................................................................................... 45
DECLARATIONS OF INTEREST..................................................................................................................................................................... 45
SOURCES OF SUPPORT............................................................................................................................................................................... 45
DIFFERENCES BETWEEN PROTOCOL AND REVIEW.................................................................................................................................... 46
INDEX TERMS............................................................................................................................................................................................... 46
Exercise-based cardiac rehabilitation for adults with stable angina (Review) i

Informed decisions.
[Intervention Review]
Exercise-based cardiac rehabilitation for adults with stable angina
Linda Long1, Lindsey Anderson1, Alice M Dewhirst1, Jingzhou He2, Charlene Bridges3, Manish Gandhi2, Rod S Taylor1
1Institute of Health Research, University of Exeter Medical School, Exeter, UK. 2Cardiology, Royal Devon & Exeter NHS Foundation Trust
Hospital, Exeter, UK. 3Farr Institute of Health Informatics Research, University College London, London, UK
Contact: Rod S Taylor, Institute of Health Research, University of Exeter Medical School, Exeter, UK. [email protected].
Editorial group: Cochrane Heart Group.

Publication status and date: New, published in Issue 2, 2018.
Citation: Long L, Anderson L, Dewhirst AM, He J, Bridges C, Gandhi M, Taylor RS. Exercise-based cardiac rehabilitation for adults with
stable angina. Cochrane Database of Systematic Reviews 2018, Issue 2. Art. No.: CD012786. DOI: 10.1002/14651858.CD012786.pub2.
ABSTRACT
Background
A previous Cochrane review has shown that exercise-based cardiac rehabilitation (CR) can benefit myocardial infarction and post-
revascularisation patients. However, the impact on stable angina remains unclear and guidance is inconsistent. Whilst recommended in the
guidelines of American College of Cardiology/American Heart Association and the European Society of Cardiology, in the UK the National
Institute for Health and Care Excellence (NICE) states that there is "no evidence to suggest that CR is clinically or cost-effective for managing
stable angina".
Objectives
To assess the effects of exercise-based CR compared to usual care for adults with stable angina.
Search methods
We updated searches from the previous Cochrane review 'Exercise-based cardiac rehabilitation for patients with coronary heart disease'
by searching the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, DARE, CINAHL and Web of Science on 2
October 2017. We searched two trials registers, and performed reference checking and forward-citation searching of all primary studies
and review articles, to identify additional studies.
Selection criteria
We included randomised controlled trials (RCTs) with a follow-up period of at least six months, which compared structured exercise-based
CR with usual care for people with stable angina.
Data collection and analysis

Two review authors independently assessed the risk of bias and extracted data according to the Cochrane Handbook for Systematic Reviews
of Interventions. Two review authors also independently assessed the quality of the evidence using GRADE principles and we presented
this information in a 'Summary of findings' table.
Main results
Seven studies (581 participants) met our inclusion criteria. Trials had an intervention length of 6 weeks to 12 months and follow-up length
of 6 to 12 months. The comparison group in all trials was usual care (without any form of structured exercise training or advice) or a no-
exercise comparator. The mean age of participants within the trials ranged from 50 to 66 years, the majority of participants being male
(range: 74% to 100%). In terms of risk of bias, the majority of studies were unclear about their generation of the randomisation sequence
and concealment processes. One study was at high risk of detection bias as it did not blind its participants or outcome assessors, and
two studies had a high risk of attrition bias due to the numbers of participants lost to follow-up. Two trials were at high risk of outcome
Exercise-based cardiac rehabilitation for adults with stable angina (Review) 1

Informed decisions.
reporting bias. Given the high risk of bias, small number of trials and participants, and concerns about applicability, we downgraded our
assessments of the quality of the evidence using the GRADE tool.
Due to the very low-quality of the evidence base, we are uncertain about the effect of exercise-based CR on all-cause mortality (risk ratio
(RR) 1.01, 95% confidence interval (CI) 0.18 to 5.67; 195 participants; 3 studies; very low-quality evidence), acute myocardial infarction
(RR 0.33, 95% CI 0.07 to 1.63; 254 participants; 3 studies; very low-quality evidence) and cardiovascular-related hospital admissions (RR
0.14, 95% CI 0.02 to 1.1; 101 participants; 1 study; very low-quality evidence). We found low-quality evidence that exercise-based CR may
result in a small improvement in exercise capacity compared to control (standardised mean difference (SMD) 0.45, 95% CI 0.20 to 0.70; 267
participants; 5 studies, low-quality evidence). We were unable to draw conclusions about the impact of exercise-based CR on quality of life
(angina frequency and emotional health-related quality-of-life score) and CR-related adverse events (e.g. skeletomuscular injury, cardiac
arrhythmia), due to the very low quality of evidence. No data were reported on return to work.
Authors' conclusions
Due to the small number of trials and their small size, potential risk of bias and concerns about imprecision and lack of applicability, we
are uncertain of the effects of exercise-based CR compared to control on mortality, morbidity, cardiovascular hospital admissions, adverse
events, return to work and health-related quality of life in people with stable angina. Low-quality evidence indicates that exercise-based
CR may result in a small increase in exercise capacity compared to usual care. High-quality, well-reported randomised trials are needed to
assess the benefits and harms of exercise-based CR for adults with stable angina. Such trials need to collect patient-relevant outcomes,
including clinical events and health-related quality of life. They should also assess cost-effectiveness, and recruit participants that are
reflective of the real-world population of people with angina.
PLAIN LANGUAGE SUMMARY
Exercise-based cardiac rehabilitation for people with stable angina
Review question
Is exercise-based cardiac rehabilitation for people with stable angina helpful in improving their condition?
Background
Stable angina is a form of chronic heart disease associated with ill health and increased death rates. Exercise-based cardiac rehabilitation
is a programme that helps people with heart disease gain better health. It usually involves exercising and receiving advice on ways to
improve health and takes place at hospitals or within the community or at home. The National Institute for Health and Care Excellence in
the United Kingdom does not currently recommend cardiac rehabilitation programmes for people with angina, while European and United
States guidelines do. In this review, we look at whether cardiac rehabilitation is helpful to people with stable angina. Specifically we assess
whether cardiac rehabilitation is helpful in reducing death rates, the need for surgery, repeated heart attacks, healthcare usage and costs;
and improving quality of life, physical fitness levels, and symptoms of angina.
Study characteristics
The evidence is current to 2 October 2017. We included seven studies that randomly allocated a total of 581 participants with stable angina
to either receive cardiac rehabilitation or no exercise control. We identified that there are no ongoing randomised studies. The average
age of participants ranged from 50 to 66 years. The majority of people recruited were middle-aged men. Most studies were carried out in
European countries and one study in India. Cardiac rehabilitation was most commonly delivered in a combined setting of home and centre
or hospital. The length of the cardiac rehabilitation programmes ranged from six weeks to one year.
Key results
There is insufficient evidence to assess the impact of exercise-based cardiac rehabilitation on the outcomes that matter most to patients:
risks of death, heart attack, or future cardiac operation and quality of life. There may be a small improvement in physical fitness following
exercise-based cardiac rehabilitation compared to usual treatment. There was no evidence about returning to work.
Quality of the evidence
Due to the poor reporting, high risk of bias and small number of trials and participants included in this review, our assessment of the quality
of the evidence ranged from low to very low across outcomes. For low-quality evidence our confidence in the result is limited, and for very
low-quality evidence we have very little confidence in the result.
Conclusions
We need more high-quality studies in more representative populations of people with stable angina. These studies should collect outcomes
of relevance to patients and healthcare decision-makers. Then we will be able to better assess the impact of exercise-based cardiac
rehabilitation.

SUMMARY OF FINDINGS
Summary of findings for the main comparison. Exercise-based cardiac rehabilitation compared to usual care for adults with stable angina
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Exercise-based cardiac rehabilitation (CR) compared to usual care for patients with stable angina
Patient or population: adults with stable angina

Setting: hospital, outpatient clinic, community or home-based environment
Intervention: exercise-based cardiac rehabilitation
Better health.
Informed decisions.
Trusted evidence.
Comparison: usual care (standard medical care but without any structured training or advice on structured exercise training)
Outcomes Anticipated absolute effects* (95% Relative effect № of partici- Quality of the Comments
CI) (95% CI) pants evidence
(studies) (GRADE)
Risk with usual Risk with exer-
care cise-based car-
diac rehabilita-
tion
All-cause mortality Study population RR 1.01 195 ⊕⊝⊝⊝ We are uncertain about the effect of
(0.18 to 5.67) (3 RCTs) VERY LOW 1,2,3 exercise-based CR on all-cause mortal-
Follow-up: 12 months 20 per 1,000 21 per 1,000 ity compared to usual care.
(4 to 116)
Acute myocardial infarction Study population RR 0.33 254 ⊕⊝⊝⊝ We are uncertain about the effect of
(AMI) (0.07 to 1.63) (3 RCTs) VERY LOW 2,3,5 exercise-based CR on AMI compared to
39 per 1,000 13 per 1,000 usual care.
Follow-up: 12 months (3 to 64)
Exercise capacity The mean exercise capacity in the intervention groups 267 ⊕⊕⊝⊝ Using Cohen's rule of thumb a SMD
was 0.45 standard deviations higher (5 RCTs) LOW 4,6 of 0.2 represents a small effect, 0.5 a
(assessed using a variety of out- (0.2 higher to 0.7 higher) moderate effect and 0.8 a large effect
comes including VO2 max and

between groups (Cohen 1988).
duration of exercise)
Exercise-based CR may slightly im-
Follow-up: range 6 to 12 prove exercise capacity compared to
months usual care.
Cardiovascular-related hospital Study population RR 0.14 101 ⊕⊝⊝⊝ We are uncertain about the effect of
admissions (1 RCT) VERY LOW 2,7,9 exercise-based CR on cardiovascu-
(assessed with: combined clin- 140 per 1000 20 per 1000 (2 to (0.02 to 1.1) lar-related hospital admissions com-
ical endpoint (cardiac death, 154) pared to usual care.
stroke, CABG, PCI, AMI, worsen-
ing angina with objective evi-
3
dence resulting in hospitalisa-
tion))
Follow-up: 12 months
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Health-related quality of life One study showed improvement in Not estimable 94 ⊕⊝⊝⊝ We are uncertain about the effect of
(assessed with: Seattle Angina emotional score at 6-week follow up, VERY LOW 8,9 exercise-based CR on quality of life
Questionnaire and The MacNew and benefits in angina frequency and (1 RCT) compared to usual care.
Questionnaire) social HRQL score at 6 months fol-
Follow-up: range 6 weeks to 6 low-up.
Better health.
Informed decisions.
Trusted evidence.
months
Return to work No studies were found that looked at return to work.
Adverse events (e.g. skeleto- Only one study looked at adverse Not estimable 101 ⊕⊝⊝⊝ We are uncertain about the effect of
muscular injury) events and reported that there were VERY LOW 2,7,9 exercise-based CR on adverse events
no adverse events during the exer- (1 RCT) compared to usual care.
Follow-up: 12 months cise-based CR.
*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).
AMI: acute myocardial infarction; CABG: coronary artery bypass graft; CI: confidence interval; CR: cardiac rehabilitation; HRQL: health-related quality of life; PCI: percuta-
neous coronary intervention;RCT: randomised controlled trial; RR: risk ratio
GRADE Working Group grades of evidence

High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is sub-
stantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
1 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
2 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
3 Imprecise due to small number of participants (less than 300) and confidence intervals 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
4 Some concerns 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
5 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
6 Imprecise due to small number of participants (less than 300) therefore quality of evidence downgraded by one level
7 Some concerns with random sequence generation, allocation concealment and selective reporting; bias likely, therefore quality of evidence downgraded by one level
8 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
4
Informed decisions.
9 Imprecise due to very small number of participants therefore quality of evidence downgraded by two levels

Informed decisions.
BACKGROUND physical, mental and social conditions, so that the patients may,
by their own efforts, preserve or resume optimal functioning in
Description of the condition their community and through improved health behaviour, slow
or reverse progression of disease" (BACPR 2012). A complex
Angina pectoris is traditionally defined as a pain, discomfort or
intervention that may involve a variety of therapies, CR includes
tightness, most commonly felt in the chest, that may radiate to the
exercise, risk factor education, behaviour change, psychological
neck, jaw and arms. It is typically reproducible, gradual in onset
support, and strategies that are aimed at targeting traditional
and offset and may be associated with breathlessness and nausea.
risk factors for cardiovascular disease. Cardiac rehabilitation
Angina occurs when the coronary arteries become narrowed and
is an essential part of contemporary heart disease care and
myocardial oxygen demand exceeds oxygen supply. This leads
is considered a priority in countries with a high prevalence
to reversible myocardial ischaemia or hypoxia, particularly when
of CHD. Based on evidence from previous meta-analyses and
oxygen demands are high, such as during exercise and stress.
systematic reviews, exercise-based CR following a cardiac event
The complex mechanisms leading to symptoms of angina are not
is a Class I recommendation from the American College of
entirely understood. Importantly, acidosis results from myocardial
Cardiology/American Heart Association (Fihn 2012; Smith 2011)
ischaemia, causing the release of metabolites such as adenosine
and the European Society of Cardiology (Montalescot 2013). Service
and bradykinin that stimulate the sympathetic afferent nerve
provision, though predominantly hospital-based, varies markedly,
pathway, eventually transmitting the painful stimuli to the brain
and referral, enrolment and completion are sub-optimal, especially
(Crea 1990; Foreman 1999).
among women and older people (Beswick 2004; Clark 2012). Home-
It was estimated that in 2013 over 1.3 million people in the UK had based CR programmes have been increasingly introduced to widen
angina (BHF 2014) and it was thought to affect approximately 112 access and participation (Taylor 2010), and interventions aimed at
million people, or 1.6% of the population worldwide (Vos 2012). improving patient uptake and adherence to CR programmes have
Data suggest an annual incidence of uncomplicated angina of 1.0% been adopted (Karmali 2014).
in western men aged 45 to 65 years, with a slightly higher incidence
Exercise-based CR in selected patient groups is remarkably safe.
in women in this age bracket (Hemingway 2006; NHLBI 2012).
An observational study of more than 25,000 participants who
Incidence increases with age in both men and women aged 75
underwent CR following cardiac surgery, recent percutaneous
to 84 years, reaching almost 4% (Hemingway 2006). However, age
coronary intervention (PCI) or with other coronary and non-
standardised angina prevalence decreased globally from 21.9 to
coronary conditions reported one cardiac event for 50,000 hours
20.3 per 100,000 in males and from 17.7 to 15.9 in females between
of exercise training, equivalent to 1.3 cardiac arrests per million
1990 and 2010 (Moran 2014).
patient-hours (Pavy 2006). An earlier study reported one case of
Angina is considered stable when there is no increase in frequency ventricular fibrillation per 111,996 patient-hours of exercise and
or severity of symptoms (NICE 2011). However, the transition one myocardial infarction (MI) per 294,118 patient-hours (Van
from stable to unstable angina, is in reality, a continuum and Camp 1986). However, people with unstable angina, uncontrolled
without clear boundaries (Montalescot 2013). We define stable ventricular arrhythmia, and severe heart failure (New York Heart
angina in this review as chest pain and associated symptoms Association level 4) have been considered at high risk, and careful
precipitated by activity (e.g. running, walking) with minimal or non- assessment by an experienced clinician is recommended before
existent symptoms at rest. We define unstable angina as chest they engage in the exercise component of CR (BACPR 2012).
pain and other symptoms of cardiovascular disease which are of Historically, CR has often not been routinely offered to people
new onset (previous four to six weeks), worsening, becoming more with stable angina. Indeed, 20% of all CR programmes included in
frequent and/or occurring at rest or minimal exertion. Despite the the 2009 UK national audit of CR, actively excluded stable angina
term "stable", a diagnosis of stable angina is a chronic medical (Lewin 2010). In the 2016 National Audit for Cardiac Rehabilitation
condition associated with a low but appreciable incidence of acute Annual Report, it was outlined that angina referrals accounted for
coronary events and increased mortality. Management options less than 4% of the 79,442 people receiving CR, although 24% of all
include lifestyle advice, drug therapy and revascularisation, which participants were reported as having co-morbid angina at the point
aim to minimise symptoms, and improve quality of life and long- of entry to their CR programme (NACR 2016).
term morbidity and mortality.
How the intervention might work
Although it can be precipitated by a number of conditions, stable The precise mechanisms by which CR improves mortality in
angina is considered to be a symptom of coronary heart disease people with CHD has not been fully elucidated. Exercise training
(CHD), which is the single most common cause of global mortality, has been shown to have direct benefits on the heart and
and accounts for approximately one-third of all deaths worldwide, coronary vasculature, including myocardial oxygen demand,
placing a major economic and resource burden on healthcare endothelial function, autonomic tone, coagulation and clotting
systems (WHO 2014). factors, inflammatory markers, and the development of coronary
collateral vessels (Clausen 1976; Hambrecht 2000; Lavie 2015).
Description of the intervention However, it has been suggested that approximately half of the 28%
As previously described (Anderson 2016), many definitions of reduction in cardiac mortality in people with CHD may also be
cardiac rehabilitation (CR) have been proposed (for example, mediated via the indirect effects of exercise through improvements
BACPR 2012; Balady 2011; WHO 1993).The following definition in the risk factors for atherosclerotic disease (i.e. total cholesterol,
encompasses the key concepts of CR: "The coordinated sum of smoking and blood pressure) (Taylor 2006). Further reductions in
activities required to influence favourably the underlying cause mortality may be attributed to reductions in psychological stress,
of cardiovascular disease, as well as to provide the best possible including depression, anxiety and hostility (Lavie 2011).

Informed decisions.
Why it is important to do this review Types of participants

The American College of Cardiology/American Heart Association We included adult men and women aged 18 years or older who
give a Class I recommendation that medically supervised CR had been diagnosed with coronary heart disease (CHD) and had
programmes and physician-directed, home-based programs are stable angina. We included participants who presented with stable
offered to at-risk people with stable CHD including those with or exertional angina (effort-induced chest discomfort), who were
stable angina, at first diagnosis (Fihn 2012). Similarly, the European being treated with medical anti-anginal therapy and who may have
Society of Cardiology recommends that people with stable had a previous myocardial infarction (MI), coronary artery bypass
CHD, including stable angina, should undergo "moderate-to- graft (CABG) or percutaneous coronary intervention (PCI). However,
vigorous intensity aerobic exercise training ≥ 3 times a week we excluded people in the immediate period following such an
and for 30 min per session" (Montalescot 2013). The British event, i.e. within three months of MI, PCI or CABG. We also excluded
Association for Cardiovascular Prevention and Rehabilitation people with unstable angina (pain at rest) and those with refractory
(BACPR), recommend CR for people following a cardiac event, angina for whom revascularisation was planned.
with heart failure, and to those with other established forms of
cardiovascular disease, including stable angina (BACPR 2012). We included studies with a mixed population of people with CHD,
where the data for people with stable angina and without any
Despite these guidelines, the current National Institute for Health confounding co-morbidities were reported separately. We also
and Care Excellence (NICE) guideline for the management of stable included studies where the majority of the participant sample were
angina (CG126) states that there is "no evidence to suggest that reported to have stable angina, regardless of whether data for this
CR is clinically or cost-effective for managing stable angina" (NICE sub-population was reported separately.
2011). NICE report that while there has been limited research on
short-term outcomes such as a change in diet or exercise levels, the Types of interventions
effect on morbidity and mortality has not been studied, and they We sought exercise-based CR interventions either alone or as an
highlight research into CR for this patient population as one of their element of a comprehensive CR programme including components
key research recommendations (NICE 2011). such as health education, behavioural and psychological
interventions or surgery in addition to the exercise intervention.
Previous Cochrane reviews have looked at the effect of exercise- The exercise-based intervention could have been supervised or
based CR in people with CHD (Anderson 2016), heart failure (Taylor unsupervised, and conducted in a hospital, community or home-
2014) and after heart valve surgery (Sibilitz 2016). A meta-analysis based environment.
of 63 trials, which randomised 14,486 people with CHD (including
those with angina) to exercise-based CR or a no-exercise control, The control group received usual care which could have included
showed that exercise-based CR led to a reduction in cardiovascular standard medical care (such as drug therapy, health education,
mortality (risk ratio (RR) 0.74, 95% CI 0.64 to 0.86), hospital behavioural or psychological interventions, or surgery) but without
admissions (RR 0.82, 95% CI 0.70 to 0.96) and health-related quality any structured exercise training or advice on structured exercise
of life (Anderson 2016). However, many trials in this review were training.
in a mixed population of people with CHD (Anderson 2016). Given
the NICE key research recommendations, we believe there is a Types of outcome measures
good case for separating out the evidence for CR in stable angina.
We were interested in the following outcomes with a minimum
Our scoping searches have confirmed that no systematic review
follow-up of six months.
has been previously conducted which has specifically assessed the
impact of CR in a population in people with stable angina. Primary outcomes
OBJECTIVES • All-cause mortality
• Morbidity (myocardial infarction (MI); revascularisation (CABG
To assess the effects of exercise-based cardiac rehabilitation or PCI); or all-cause hospital admissions)
compared to usual care for adults with stable angina.
• Health-related quality of life (HRQL) assessed using validated
METHODS instruments (e.g. 36-Item Short Form Health Survey (SF-36),
EQ-5D)
Criteria for considering studies for this review • Exercise capacity assessed by validated outcome measure (e.g.
VO2peak, 6-minute walk test)
Types of studies
• Cardiovascular-related hospital admissions
We included randomised controlled trials (RCTs) (individual patient
allocation, cluster allocation, or cross-over) which compared Secondary outcomes
exercise-based CR with a usual care or a no exercise comparator. We
• Severity of angina, assessed using validated instruments (e.g.
only included RCTs with a follow-up period of at least six months,
Canadian Cardiovascular Society grading of angina pectoris;
in order to reflect current practice of guideline- and policy-writing,
New York Heart Association Functional Classification of Angina)
which is driven by long-term health benefits. Where studies had
mixed populations, we included those in which 50% or more of • Reported adverse events (clinical events relating to CR, e.g.
participants had stable angina. skeletomuscular injuries or arrhythmias, or withdrawal from the
intervention)
• Return to work
• Costs

Informed decisions.
Reporting one or more of the outcomes listed here in the trial was unclear) or 'do not retrieve'. If there were any disagreements, three
not an inclusion criterion for the review. additional authors (RST, JH and MG) were asked to arbitrate. We
retrieved the full-text study reports/publications and two review
Search methods for identification of studies authors (AD and LA) independently screened the full-texts and
identified studies for inclusion, and recorded reasons for exclusion
Electronic searches
of the ineligible studies. If there were any disagreements, three
We identified trials through systematic searches of the following review authors (RST, JH and MG) were asked to arbitrate. We
bibliographic databases up to 9 September 2016 and then updated identified and excluded duplicates and collated multiple reports of
this with a further search up to 2 October 2017: the same study so that each study rather than each report was the
unit of interest in the review. We recorded the selection process in
• CENTRAL Issue 9 of 12, 2017 (Cochrane Library) sufficient detail to complete a PRISMA flow diagram (Figure 1) and
• Database of Abstracts of Reviews of Effects (DARE) Issue 2 of 4, Characteristics of included studies table.
2015 (last issue, now ceased publication) (Cochrane Library)
• Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Data extraction and management
MEDLINE Daily and MEDLINE (Ovid, 1946 to 2 October 2017) The study characteristics and outcome data from included studies
• Embase (Ovid, 1980 to 2017 Week 40) were extracted independently by two reviewers (JH and shared
• CINAHL Plus (EBSCO, 1937 to 2 October 2017) between AD and LA), using a standardised data extraction form
• Conference Proceedings Citation Index—Science (CPCI-S) in which had been piloted on at least one of the studies included
Web of Science Core Collection (Thomson Reuters, 1990 to 2 in the review. Any disagreements were resolved by consensus
October 2017). or by consulting a third reviewer (RST). The following study
characteristics were extracted.
The search strategies were designed with reference to those of a
previous related systematic review of exercise-based CR for CHD • Methods: study design, total duration of study, number of study
(Anderson 2016a). The preliminary search strategy for MEDLINE centres and location, study setting, withdrawals, and date of
(Ovid) was adapted for use in the other databases (Appendix 1). study.
We searched databases using a strategy combining selected MeSH • Participants: N, mean age, age range, gender, severity of
terms and free-text terms relating to exercise-based rehabilitation condition, diagnostic criteria, inclusion criteria, and exclusion
and stable angina, with filters applied to limit to RCTs. We criteria.
used the Cochrane sensitivity-maximising RCT filter for MEDLINE, • Interventions: intervention, comparison, and co-interventions.
and applied terms recommended in the Cochrane Handbook for • Outcomes: primary and secondary outcomes specified and
Systematic Reviews of Interventions for Embase (Lefebvre 2011). We collected, and time points reported.
applied adaptations of this filter to CINAHL and Web of Science. • Notes: funding for trial, and notable conflicts of interest of trial
We translated the MEDLINE search strategy for use with the authors.
other databases using the appropriate controlled vocabulary as
applicable. AD transferred data into the Review Manager (RevMan 2014) file and
LL double-checked that data were entered correctly by checking
We searched all databases from their inception to the present, the study characteristics for accuracy against the study report.
imposed no restriction on language of publication and gave
consideration to variations in terms used and spellings of terms Assessment of risk of bias in included studies
in different countries so that the search strategy would not miss
studies because of such variations. LL, JH and AD independently assessed risk of bias for each study
using the criteria outlined in the Cochrane Handbook for Systematic
Searching other resources Reviews of Interventions (Higgins 2011). Any disagreements were
resolved by consensus and decisions were independently checked
We hand-searched reference lists, and conducted forward citation by a third review author (RT). We assessed the risk of bias according
searching of all primary studies and review articles for additional to the following domains.
references not identified by the electronic searches. We conducted
a search of trial registers on 30 November 2016: World • Random sequence generation.
Health Organization International Clinical Trials Registry Platform • Allocation concealment.
(WHO ICTRP; http://www.who.int/ictrp/en) and ClinicalTrials.gov
• Blinding of outcome assessment.
(https://clinicaltrials.gov) for ongoing clinical trials. We also
contacted experts in the field for unpublished and ongoing trials • Incomplete outcome data.
and contacted trial authors where necessary for any additional • Selective outcome reporting.
information. We also examined any relevant retraction statements • Other (specifically sources of funding and conflicts of interest).
and errata for included studies.
We also assessed two additional domains: whether the study
Data collection and analysis groups were balanced at baseline, and if the study groups received
comparable care (apart from the exercise component of the
Selection of studies
intervention). These criteria, agreed upon in advance by the review
Two review authors (AD and LA) independently screened titles and authors, have not been validated but have been used to assess
abstracts of all the potential studies we identified as a result of the quality in previous Cochrane reviews (Anderson 2016; Anderson
search and coded them as 'retrieve' (eligible, or potentially eligible/

Informed decisions.
2016a; Brown 2011; Sibilitz 2016; Taylor 2014; Taylor 2015). We occurred, and 3) appropriate statistical approaches had been used.
assessed these two domains as follows. If cluster trials had been included, consideration would have been
given to whether the reported data analysis had appropriately
Groups balanced at baseline taken account of the aggregate nature of the data.
• Low risk of bias: the characteristics of the participants in the
Dealing with missing data
intervention and control groups at baseline are reported to be
comparable or can be judged to be comparable (e.g. baseline We contacted investigators or study sponsors to verify key study
data reported in a table in the study report) in terms of likely characteristics and obtain missing numerical outcome data where
main prognostic factors. possible (for example when a study was identified as abstract only).
• Unclear risk of bias: whether the characteristics of the Where this was not possible, and the missing data were not thought
participants in the intervention and control groups are balanced to introduce serious bias, we explored the impact of including such
at baseline is not reported, and reported information is studies on the overall assessment of results by a sensitivity analysis.
inadequate to assess this (e.g. no table of baseline data in the
study report). Assessment of heterogeneity
• High risk of bias: there is evidence of substantive imbalance We explored heterogeneity amongst included studies qualitatively
in the baseline characteristics of the intervention and control (by comparing the characteristics of included studies) and
groups with regard to likely major prognostic factors. quantitatively (using the Chi2 test of heterogeneity and I2 statistic).
We considered that an I2 between 50% and 90% may represent
Groups received comparable treatment (except exercise) substantial heterogeneity (Higgins 2011).
• Low risk of bias: all co-interventions were delivered equally
across intervention and control groups. Assessment of reporting biases
• Unclear risk of bias: information to assess whether co- If we had been able to pool more than 10 trials, we had intended to
interventions were delivered equally across groups was create and examine a funnel plot and use the Egger test (Egger 1997)
insufficient. to explore possible small-study biases for the primary outcomes.
• High risk of bias: the co-interventions were not delivered equally However, this was not possible owing to the small number (n = 7)
across intervention and control groups. of included trials.
We graded each potential source of bias as high, low, or unclear and Data synthesis
provided a quote from the study report together with a justification We undertook a meta-analyses only where this was meaningful,
for our judgement in the 'Risk of bias' table. We summarised i.e. if the treatments, participants and the underlying clinical
the 'Risk of bias' judgements across different studies for each of question were similar enough for pooling to make sense. Data
the domains listed. Where information on risk of bias relates to from each study were pooled using a fixed-effect model, except
unpublished data or correspondence with an author, we noted this where substantial heterogeneity existed. If possible, we intended
in the 'Risk of bias' table. to pool the results for HRQL using a standardised mean difference.
If there was evidence of substantial statistical heterogeneity (P
When considering treatment effects, we took into account the risk
value less than 0.10, I2 above 50%) associated with an effect
of bias for the studies that contributed to that outcome.
estimate, we applied a random-effects model, which provided a
Assessment of bias in conducting the systematic review more conservative statistical comparison of the difference between
intervention and control because a confidence interval around
We conducted the review according to the published protocol and the effect estimate is wider than a confidence interval around a
reported any deviations from it, if occurring, in the Differences fixed-effect estimate. If a statistically significant difference was still
between protocol and review section of the systematic review. present using the random-effects model, we also reported the
fixed-effect pooled estimate and 95% confidence interval because
Measures of treatment effect
of the tendency of smaller trials, which are more susceptible
We processed data in accordance with the Cochrane Handbook for to publication bias, to be over-weighted with a random-effects
Systematic Reviews of Interventions (Higgins 2011). We analysed analysis (Heran 2008a; Heran 2008b).
dichotomous data as a risk ratio (RR) with 95% confidence intervals
(CIs) and continuous data as mean difference (MD) or standardised We processed data in accordance with the Cochrane Handbook for
mean difference (SMD) with 95% CIs. For outcomes that were Systematic Reviews of Interventions (Higgins 2011). We completed
measured by studies in a variety of ways (for example exercise data synthesis and analyses using Review Manager 5.3 software
capacity), the SMD with 95% CIs was used as the summary statistic. (RevMan 2014), and we planned to conduct a meta-regression
We entered data presented as a scale with a consistent direction of analysis using the 'metareg' command in Stata version 14.2
effect. (StataCorp 2013).
Unit of analysis issues 'Summary of findings' table
In accordance with Section 16.4 of the Cochrane Handbook for Two reviewers (LL and RST) independently employed the Grading
Systematic Reviews of Intervention (Higgins 2011), we included data of Recommendations Assessment, Development and Evaluation
from both periods of any cross-over trials identified, assuming (GRADE) approach (Schünemann 2011) to interpret result findings.
1) there had been a wash-out period considered long enough to We used the five GRADE considerations (study limitations,
reduce carry-over, 2) no irreversible events such as mortality had consistency of effect, imprecision, indirectness, and publication

Informed decisions.
bias) to assess the quality of a body of evidence as it related to the We sought to extract results of subgroup analyses, including
studies that contributed data to the meta-analyses and narrative participant-level subgroup analyses, if reported by individual
summaries for the pre-specified outcomes. Any discrepancies included studies, for example if a trial reports whether there
in judgements were resolved through discussion. One reviewer was a difference in the effectiveness of CR between males and
(LL) used GRADEpro GDT 2015 to import data from Review females. Given the anticipated small ratio of trials to covariates,
Manager to create a 'Summary of findings' table using the we had anticipated a meta-regression limited to univariate analysis
following pre-specified outcomes: all-cause mortality; myocardial (Higgins 2011). However, given the small number of trials (N = 7)
infarction (MI); all-cause hospital admissions; HRQL; return to work, included in this review, neither meta-regression or a stratified meta-
exercise capacity and adverse events. We justified all decisions analysis were deemed appropriate (Higgins 2011).
to downgrade the quality of evidence using footnotes, and made
comments to aid readers' understanding of the review where Sensitivity analysis
necessary. We had planned to compare meta-analysis results including all
studies versus only including those studies judged to have overall
Subgroup analysis and investigation of heterogeneity
low risk of bias (low risk in four or more domains). We had also
We anticipated length of follow-up to be a driver of intervention intended to conduct a sensitivity analysis excluding studies at high
effect, and therefore sought to stratify meta-analysis of each risk of bias and to produce funnel plots and tests of asymmetry to
outcome according to the length of trial duration, i.e. 'short-term' assess possible publication bias (Egger 1997). However, due to the
follow-up (6 to 12 months); 'medium-term' follow-up (13 to 36 small number of trials included in this review (N = 7) neither the
months); and 'long-term' follow-up (more than 36 months). We sensitivity analysis or funnel plots were undertaken.
also aimed to undertake univariate meta-regression to explore
heterogeneity and examine potential treatment effect modifiers. Reaching conclusions
We sought to test the a priori hypotheses that there may be We based our conclusions only on findings from the quantitative or
differences in the effect of exercise-based CR on all-cause mortality, narrative synthesis of included studies for this review. We avoided
morbidity, health related quality of life and exercise capacity across making recommendations for practice and our implications for
particular subgroups (Anderson 2016): research suggested priorities for future research and outlined what
the remaining uncertainties were in the area.
• type of CR: exercise-only CR versus comprehensive CR
(categorical variable); RESULTS
• 'dose' of exercise intervention (dose = number of weeks of
exercise training x average number of sessions per week x Description of studies
average duration of session in minutes): dose 1000 units or
more, versus dose less than 1000 units (continuous variable); See Characteristics of included studies and Characteristics of
excluded studies.
• follow-up period (continuous variable);
• year of publication: pre-1995 and post-1995 (continuous Results of the search
variable)—timing reflects the introduction of modern-day drug
therapy for the management of CHD; The electronic search yielded 3,841 titles and abstracts (3,585
for September 2016; 256 for October 2017 update). Following
• sample size (continuous variable); screening, 24 studies were evaluated for formal inclusion or
• setting: home- or centre-based CR (categorical variable); exclusion by retrieving the full-text publications. A total of seven
• study location: continent (categorical variable); randomised controlled trials (RCTs) were included for review.
• mean age of participants (continuous variable); Backwards and forwards searching of the reference lists of the
• percentage of male participants (continuous variable); and eligible publications did not detect any further publications for
inclusion. One ongoing trial protocol was identified (NCT01147952).
• percentage of post-MI participants (continuous variable).
The study selection process is summarised in the flow diagram
(Figure 1).

Informed decisions.
Figure 1. PRISMA flow diagram of trial selection
Included studies trials ranged from 50 to 66 years. All studies recruited a majority of
males (range: 74% to 100%), with four recruiting men only.
Overall, we included seven trials (eight publications) (Devi 2014;
Hambrecht 2004; Jiang 2007; Manchanda 2000; Raffo 1980; Schuler One study was based solely on a hospital-based CR programme
1992; Todd 1991) with 581 participants. One trial (Schuler 1992) (Todd 1991). Three studies initiated CR in the hospital followed
reported results from two publications in the same trial population. by home-based delivery (Hambrecht 2004; Manchanda 2000; Raffo
The original study (Schuler 1992) was included and analysed in 1980). Two studies were entirely home-based (Devi 2014; Jiang
this review. Although included, one trial provided no outcome data 2007) and used an on-line exercise goal setting intervention. In
relevant to this review (Jiang 2007). Detailed study characteristics all the included studies the primary mode of exercise was aerobic
and risks of bias assessment for the seven included studies are exercise - typically walking and cycling. The dose of exercise varied
provided in the Characteristics of included studies table. considerably across studies, in terms of overall duration (range:
6 weeks to 12 months), frequency (daily), session length (range:
Four studies (Devi 2014; Hambrecht 2004; Raffo 1980; Todd 1991)
11 to 90 minutes per session) and intensity (defined as 'moderate
were exercise-only intervention studies and three studies (Jiang
intensity' or 70% to 75% maximal heart rate). Intervention
2007; Manchanda 2000; Schuler 1992) were comprehensive cardiac
adherence and fidelity were either poorly reported or not reported
rehabilitation (CR), i.e. exercise plus education interventions. Five
at all so we were not able to assess the actual amounts of exercise or
studies were performed in European countries, one in China (Jiang
other CR that the CR participants undertook. Six studies compared
2007) and one in India (Manchanda 2000). All studies were relatively
CR to usual care which included medication, education and advice
small in size ranging from 24 to 113 participants with a median of
about diet and risk factors. One trial (Hambrecht 2004) compared
86 participants. The median intervention duration was 12 months
exercise training to percutaneous coronary intervention (PCI).
(range: 6 weeks to 12 months). Mean age of participants within the

Informed decisions.
Excluded studies Risk of bias in included studies

Seventeen studies identified in the search were excluded for Figure 2 and Figure 3 provide summaries of the risk of bias
reasons listed in the Characteristics of excluded studies table. The judgements presented as percentiles across all studies, and for
most common reasons for exclusion were a failure to include the each included study, respectively. We were unable to fully assess
appropriate population of people with stable angina. the potential for risk of bias in many instances due to there being
insufficient details reported in the studies. The reporting of details
tended to be poorer in studies published prior to 2000.
Figure 2. Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages
across all included studies.

Informed decisions.
Figure 3. Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Allocation as the studies did not describe the measures taken to ensure
concealment of group allocation.
In five studies there was an unclear risk of bias in the method
used to generate randomisation sequence (Hambrecht 2004; Blinding
Manchanda 2000; Raffo 1980; Schuler 1992; Todd 1991), with all
five studies reporting that the study was ‘randomised’ but not One study stated participants were not blinded (Devi 2014) and
providing adequate details for us to assess whether their method we judged this study to be at high risk of bias as the outcome
was appropriate. In the same five studies there was also an unclear assessments are likely to be influenced by the lack of blinding.
risk of bias in the methods used to conceal participant allocation, Blinding of participants were not reported in the remaining five

Informed decisions.
studies (Hambrecht 2004; Manchanda 2000; Raffo 1980; Schuler Effects of interventions
1992; Todd 1991). One study blinded outcome assessors to group
allocation (Hambrecht 2004) while another used procedures to See: Summary of findings for the main comparison Exercise-
ensure that assessment of exercise capacity was blinded (Raffo based cardiac rehabilitation compared to usual care for adults with
1980); both studies were judged to be at low risk of bias. The stable angina
outcome assessor was not blinded in one study and therefore we
Exercise-based cardiac rehabilitation compared to usual care
judged it to be at high risk of bias (Devi 2014). Blinding of outcome
for adults with stable angina
assessors was not reported in five studies (Jiang 2007; Manchanda
2000; Raffo 1980; Schuler 1992; Todd 1991), four of which were See Summary of findings for the main comparison. None of the
judged to be of unclear risk of bias (Jiang 2007; Manchanda 2000; included studies reported on the following outcome measures: all-
Schuler 1992; Todd 1991). cause hospital admissions or return to work.
Incomplete outcome data Primary Outcomes

Where reported, losses to follow-up and dropout were relatively Mortality
high, ranging from 15% to 58% across studies. We judged four
Three studies (Manchanda 2000; Schuler 1992; Todd 1991) (total of
studies (Devi 2014; Hambrecht 2004; Jiang 2007; Todd 1991) to be
195 participants) reported a total of four all-cause deaths with a
of low risk of bias as they described the number of and reasons
pooled risk ratio (RR) of 1.01 (95% confidence interval (CI) 0.18 to
for dropouts, which were balanced across groups. We judged
5.67, I2 = 0%, fixed-effect) (Analysis 1.1). We assessed the evidence
two studies to be at high risk of bias (Raffo 1980; Schuler 1992).
to be of very low-quality using GRADE, because of concerns about
Raffo 1980 had a high rate of dropout (58%). In Schuler 1992,
risk of bias (random sequence generation, allocation concealment,
dropouts were high in the intervention group (29%) due to patients
blinding of outcome assessment and selective reporting), concerns
experiencing adverse clinical events during exercise. One study
about applicability to review question (participants in all studies
(Manchanda 2000) was judged have unclear risk of bias as reporting
were limited to middle-aged men) and concerns about imprecision
was insufficient.
(small number of participants and confidence intervals including
Selective reporting potential for important harm or benefit); see Summary of findings
for the main comparison. One study (Schuler 1992) reported
We judged the risk of selective reporting to be unclear in five cardiovascular-related mortality in two participants in the CR group
studies where the study protocol was not available (Hambrecht and none in the control.
2004; Jiang 2007; Raffo 1980; Schuler 1992; Todd 1991). Risk of
bias was considered high in one further study where the protocol Morbidity
was not available; in the methods section of the study paper,
Myocardial infarction (MI)
participants are described as being assessed monthly but only
results at 12 months are reported (Manchanda 2000). We judged Three studies (Hambrecht 2004; Schuler 1992; Todd 1991) (total of
one study to be at high risk of bias because the primary outcome 254 participants) reported on the incidence of MI with a total of six
and two secondary outcomes described in the trial protocol were events (Analysis 1.2). There was a pooled RR of 0.33 in favour of CR
not reported (Devi 2014). (95% CI 0.07 to 1.63, I2 = 0%, fixed-effect). We assessed the evidence
to be of very low-quality using GRADE, because of concerns about
Other potential sources of bias risk of bias (sequence generation, allocation concealment, blinding
Groups balanced at baseline of outcome assessment, selective reporting, high loss to follow-up
and unbalanced groups at baseline), concerns about applicability
We considered the risk of bias associated with groups being to review question (participants in all studies were limited to
unbalanced at baseline as low for five studies (Devi 2014; middle-aged men), and concerns about imprecision (small number
Hambrecht 2004; Jiang 2007; Schuler 1992; Todd 1991). The risk of participants and confidence intervals including potential for
associated with groups being unbalanced at baseline was unclear important harm or benefit) (Summary of findings for the main
in one study (Raffo 1980). We judged one study (Manchanda 2000) comparison).
to be at high risk of bias as there was evidence of substantial
imbalance in the baseline characteristics of the intervention and Revascularisations (coronary artery bypass graft (CABG) or
control groups with regard to a likely prognostic factor (angina percutaneous coronary intervention (PCI))
episodes per week). Three studies (Hambrecht 2004; Manchanda 2000; Schuler
1992) (total of 256 participants) reported on the incidence of
Groups received comparable care (except the intervention)
revascularisations with a total of 28 events (Analysis 1.3). In total, six
We judged three studies (Hambrecht 2004; Todd 1991; Raffo 1980) revascularisations were reported among the CR groups in the three
to be at low risk of bias for this domain, because both groups studies, and 22 in the control groups, with a pooled RR for risk of
received comparable care except for the CR intervention. Three revascularisations of 0.27 in favour of CR (95% CI 0.11 to 0.64, I2 =
studies were judged to be at high risk of bias because groups did 0%, fixed-effect). We assessed the evidence to be of very low-quality
not receive comparable care (Devi 2014; Manchanda 2000; Schuler using GRADE, because of concerns about risk of bias (random
1992) and one study to be unclear risk of bias (Jiang 2007). sequence generation, allocation concealment, selective reporting
and high losses to follow-up), concerns about applicability to
review question (participants in all studies were limited to middle-
aged men) and concerns about imprecision (small number of
participants).

Informed decisions.
All-cause hospital admissions concerns about applicability to review question (participants in

No studies reported this outcome. all studies were limited to middle-aged men) and concerns about
imprecision (small number of participants). Data could not be
Health-related quality of life (HRQL) pooled in a meta-analysis because of scales used to report outcome
measures (i.e. NYHA is categorical whilst CCS is continuous).
One study (Devi 2014, 94 participants) reported HRQL using
validated instruments (Seattle angina questionnaire and MacNew Reported adverse events
questionnaire). Compared to control, improvements with CR at the
six-week follow-up were seen in emotional score (P = 0 .04) and Adverse events were only commented upon by one study
angina frequency (P = 0.002). Benefits in favour of CR in angina (Hambrecht 2004, 101 participants). The authors reported "no
frequency (P = 0.02) and social HRQL score (P = 0.02) were also adverse events" during the exercise training programme in the
observed at the six-month follow-up. We assessed the evidence for CR group. We assessed the evidence as very low quality using
this outcome as very low-quality using GRADE because of concerns GRADE because of concerns about risk of bias (random sequence
about risk of bias (blinding of outcome assessment, high losses to generation, allocation concealment and selective reporting),
follow-up, selective reporting and unbalanced groups at baseline) concerns about applicability to the review question (participants in
and concerns about imprecision (small number of participants). the study were limited to middle-aged men) and concerns about
Given the variation of outcomes it is not possible to consistently imprecision (small number of participants).
comment on the clinical importance of these results (Summary of Costs
findings for the main comparison).
One study (Hambrecht 2004) (101 participants) reported a
Exercise capacity difference in mean participant healthcare costs in favour of CR
Five studies (Hambrecht 2004; Manchanda 2000; Raffo 1980; (CR: USD 3708 versus control: USD 6086, P < 0.0001). These
Schuler 1992; Todd 1991) (total of 267 participants) reported costs included hospitalisations, repeat vascularisations, any other
exercise capacity with a range of validated measures (VO2 peak and cardiovascular events plus the costs of the provision of the CR
exercise training programme. We assessed this evidence as very
exercise duration) (Analysis 1.4). There was a small improvement
low-quality using GRADE because of concerns about risk of bias
in exercise capacity with CR compared to control (standardised
(random sequence generation, allocation concealment, high losses
mean difference (SMD) 0.45, 95% CI 0.20 to 0.70; I2 = 16%, to follow-up and selective reporting), concerns about applicability
fixed-effect). We assessed the evidence to be of low quality to review question (participants in all studies were limited to
using GRADE because of concerns about risk of bias (random middle-aged men) and concerns about imprecision (small number
sequence generation, allocation concealment, blinding of outcome of participants).
assessment and selective reporting, high losses to follow-up and
unbalanced groups at baseline) and concerns with imprecision due Return to work
to small number of participants (Summary of findings for the main
comparison). No studies reported this outcome.
Cardiovascular-related hospital admissions DISCUSSION

One study (Hambrecht 2004) (101 participants) reported that Summary of main results
one CR participant and seven control participants experienced
cardiovascular-related hospital admissions (RR 0.14, 95% CI: 0.02 This systematic review identified seven randomised trials involving
to 1.10 (Analysis 1.5)), with very low-quality evidence as assessed a total of 581 participants with a confirmed diagnosis of stable
using GRADE because of concerns about risk of bias (random angina. Five trials compared exercise-based cardiac rehabilitation
sequence generation, allocation concealment, high losses to (CR) with a no exercise control, with one trial including
follow-up and selective reporting), concerns about applicability percutaneous coronary intervention (PCI) as a comparator
to review question (participants in all studies were limited to (Hambrecht 2004). Four studies used exercise-only interventions
middle-aged men) and concerns about imprecision (small number (Devi 2014; Hambrecht 2004; Raffo 1980; Schuler 1992) and three
of participants). See Summary of findings for the main comparison. studies used comprehensive CR programmes including dietary
and risk-factor advice alongside exercise training. All exercise
Secondary Outcomes programmes were based on aerobic exercise, typically walking and
cycling.
Severity of angina
Manchanda 2000 (42 participants) reported a reduction in mean Trials had an intervention length of 6 weeks to 12 months and
New York Heart Association (NYHA) score from baseline to one follow-up length of 6 to 12 months. The comparison group in
year follow-up (2.6 to 1.4, P < 0.0001) with CR and an increase in all trials was usual care (without any form of structured exercise
mean NYHA in control (2.3 to 2.9, P = 0.004). Hambrecht 2004 (101 training or advice) or a no-exercise comparator. The mean age of
participants) reported an improvement in angina severity assessed participants within the trials ranged from 50 to 66.2 years, the
by mean Canadian Cardiovascular Society (CCS) score in both CR majority of participants being male (range: 74% to 100%).
(1.5 to 0.4, P < 0.001) and control (1.7 to 0.7, P < 0.001) We assessed Due to concerns about the small number of trials and their
the evidence as very low-quality using GRADE because of concerns small size, potential risk of bias and lack of applicability, we
about risk of bias (random sequence generation, allocation assessed the body of evidence for all but one outcome where
concealment, blinding of outcome assessment, selective reporting, data were reported to be of very low quality (all-cause mortality,
high losses to follow-up, and unbalanced groups at baseline), myocardial infarction, revascularisations, cardiovascular-related

Informed decisions.
hospital admissions, health-related quality of life, adverse events Potential biases in the review process
and costs). We are therefore uncertain about the impact of exercise-
based CR on these outcomes compared to usual care in people We conducted the review according to the methods provided
with stable angina. Based on low-quality evidence, there may be in the Cochrane Handbook for Systematic Review of Interventions
a small improvement in exercise capacity following exercise-based (Higgins 2011). We followed our peer-reviewed and pre-published
CR compared to usual care. No studies reported the outcomes of protocol in order to avoid biases during the conduct and write-up
return to work or all-cause hospital admissions. High-quality, well- of the review. In addition, we performed a comprehensive literature
reported randomised trials are needed to assess the benefits and search to identify published and unpublished trials. We contacted
harms of exercise-based CR for adults with stable angina. Such study authors for further information.
trials need to collect patient-relevant outcomes, including clinical
During the screening process, we found studies that included a
events and health-related quality of life. They should also assess
mixed population of people with coronary heart disease, but did
cost-effectiveness, and recruit participants that are reflective of the
not provide a separate reporting and analysis of the participants
real-world population of people with angina.
with stable angina. We were therefore unable to include these
studies. In many studies, we found clinical event data (e.g. mortality
Overall completeness and applicability of evidence
data) in the trial descriptions of losses to follow-up, rather than
The generalisability of this review is limited by the small number being formally stated as outcomes.
of randomised clinical trials, the low number of people with
angina and few observed events. Furthermore, included trials If in updated versions of this review we include data from studies
generally recruited primarily middle-aged men who were willing to where the majority of a mixed population had stable angina, we
participate in an exercise-based training programme and therefore will exclude these studies in a sensitivity analysis to explore their
the evidence lacks applicability to older and female populations. impact on the main analyses.
Adequately powered, high-quality, multi-centre randomised trials
An additional issue is that morbidity is considered as more than one
in a broader, more representative population of people with stable
primary outcome in our analyses (MI, CABG/PCI, all-cause hospital
angina are needed. Only one study reported cardiovascular-related
admissions). Likewise, two different dimensions of quality of life
hospital admissions, adverse events and costs, whilst a different
are reported. Therefore there are a total of eight measures of our
single study looked at health-related quality of life. None of the
primary outcomes. There is a strong risk of introducing multiplicity
included trials measured all-cause hospital admissions or return to
arising from the multiple measures of effects.
work. Future trials should collect patient-relevant outcomes and
also assess cost-effectiveness.
Agreements and disagreements with other studies or
Quality of the evidence reviews
Using GRADE methodology we assessed the quality of the evidence Our scoping searches confirmed that no systematic review has
for all outcomes where data were reported to be of very low-quality, been conducted specifically assessing the impact of exercise-based
with the exception of exercise capacity, which we assessed as being CR in a population of people with stable angina. A recent Cochrane
low quality (see Summary of findings for the main comparison). Review and meta-analysis of 63 trials, which randomised 14,486
participants with coronary heart disease (including angina) to
In terms of risk of bias, the majority of studies reported exercise-based CR or a no-exercise control, showed that exercise-
unclear randomisation processes and unclear concealment of based CR led to a reduction in cardiovascular mortality (risk ratio
randomisation. A lack of blinding resulted in a high risk of detection (RR) 0.74, 95% CI 0.64 to 0.86), hospital admissions (RR 0.82, 95% CI
bias in one trial, and high numbers of participants lost to follow- 0.70 to 0.96) and improved health-related quality of life (Anderson
up resulted in a risk of attrition bias in two trials. Two trials were 2016). The five trials of people with stable angina included in this
at high risk of outcome reporting bias. One trial was at high risk present Cochrane Review were included in this previous review.
of imbalance between groups at baseline and three were at high
risk of bias due to not receiving comparable care in addition to AUTHORS' CONCLUSIONS
the intervention. The reporting of details was poorer in the older
studies (from the year 2000 and earlier); this meant we had to assign Implications for practice
assessments of unclear risk of bias in many domains. The impact of exercise-based cardiac rehabilitation (CR) for adults
with stable angina is uncertain due to the quality of the evidence
Six outcomes (mortality, myocardial infarction, revascularisations,
being low to very low. However, it may be associated with
cardiovascular-related hospital admissions, severity of angina and
a small increase in exercise capacity compared to no exercise
costs) were assessed in trials consisting of middle-aged men
control.These findings are largely in contrast with current American
(over 50 years old), which raises concerns about indirectness and
College of Cardiology/American Heart Association and European
whether the review findings are applicable to women and older
Society of Cardiology guidelines, which recommend CR for people
populations.
with coronary heart disease including stable angina (Fihn 2012;
We also had concerns about imprecision, either due to the low Montalescot 2013; Smith 2011).
number of participants, or due to wide confidence intervals which
Implications for research
included potential for important harm or benefit (or both) for eight
outcomes (mortality, myocardial infarction, revascularisations, Given the substantial body of randomised trial evidence available
health-related quality of life, exercise capacity, cardiovascular in myocardial infarction patients, and those with post-coronary
hospital admissions, severity of angina and costs). artery bypass graft or percutaneous coronary intervention, it is

Informed decisions.
perhaps surprising that there is not currently a stronger evidence guidelines and report their methods and results according
base for exercise-based CR for stable angina. There is a need for to the Consolidated Standards of Reporting Trials (CONSORT)
well-conducted randomised controlled trials of exercise-based CR extension statement for non-pharmacological trials (Chan 2013;
compared to no intervention. Such trials should seek to recruit www.consort-statement.org).
representative samples of patients with stable angina. They should
also collect outcomes that include validated health-related quality ACKNOWLEDGEMENTS
of life measures, report clinical events including mortality and
hospital admission, and assess costs and cost-effectiveness. The review authors thank the Cochrane Heart editorial team for
their support. The review authors would also like to express their
Future trials should publish their study protocols according sincere thanks for the professional and timely handling of the
to the Recommendations for Interventional Trials (SPIRIT) review process by Helen Wakeford and Cochrane Fast-Track team.

Informed decisions.
REFERENCES
References to studies included in this review Byrkjeland 2015 {published data only}
Devi 2014 {published data only} Byrkjeland R, Njerve IU, Anderssen SH, Arnesen H, Seljeflot I,
Solheim S. Effects of exercise training on HbA1c and VO2peak
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CHARACTERISTICS OF STUDIES
Characteristics of included studies [ordered by study ID]
Devi 2014
Methods Study design: RCT
No. of centres: 1
Country: United Kingdom
Dates participants recruited: September 2008-February 2010
When randomised: after written consent and all baseline measures were collected (approximately 48
hours)
Maximum follow up: 6 months
Participants Inclusion criteria: confirmed diagnosis of stable angina, able to read and speak fluent English, had
regular access to the Internet, were computer literate and had not had conventional cardiac rehabilita-
tion within the previous year.
Exclusion criteria: unstable angina, significant cardiac arrhythmia, any co-morbidities preventing
physical activity, or were severely anxious/depressed. Severely anxious/depressed participants were
excluded by eliminating anyone with a history of being prescribed medication for either anxiety or de-
pression.
N randomised: total: 94; intervention: 48; comparator: 46 (47 randomised to comparator but 1
dropped out at baseline)
Diagnosis (% of participants):
• Angina pectoris: intervention: 100%; comparator: 100%

• Previous AMI: not reported
• Previous PCI: intervention: 35%; comparator: 49%
• Previous CABG: intervention: 21%; comparator: 14%
• Acute coronary event: not reported

Informed decisions.
Devi 2014 (Continued)

Age (mean ±SD): total: 66.24; intervention: 66.27±8.35; comparator: 66.20±10.06
Percentage male: total: 74%; intervention: 71%; comparator: 78%

Ethnicity: 91% White British, 9% other
Interventions Description: online web-based intervention with physical activity measured over a 2-day period using
a monitor.
The intervention was delivered at home via the Internet and called 'ActivateYourHeart'.
Individuals were given tailored goals for exercise.
The programme aimed to improve participants' cardiac risk profile within 4 stages and was designed to
be completed within 6 weeks. Baseline data were used to set individualised, tailored goals focused on
exercise, diet, emotions and smoking behaviour. The intervention used the following behaviour change
techniques: setting/reviewing behavioural goals, self-monitoring, feedback on behaviour, graded tasks,
social reward, providing information about health consequences, and reducing negative emotions.
Components: exercise, education and behaviour change techniques
Modality: being “physically active”. This was determined by online assessment by meeting goals (on-
line exercise diary).
Dose: individualised daily exercise (most commonly walking)
Length of session: not reported

Frequency: daily
Intensity: "moderate"
Resistance training included? Not reported
Total duration: 6 weeks
Intermittent nurse or exercise specialist support?
Programme users could initiate contact with cardiac rehabilitation nurses for advice and support via an
online email link or by joining a scheduled synchronized chat room held on a weekly basis. The cardiac
nurses were based at University Hospitals of Leicester.
Co-interventions: diet (e.g. eating more fruit/vegetables and reducing salt intake), emotions (e.g.
managing stress and other negative emotions), and smoking (e.g. reduce cigarette smoking if relevant)
goals were also set
Comparator:
Description: participants continued with treatment as usual from their GP and received no further
contact from the researcher until the 6-week follow-up. Usual care in primary care for this population
in the UK constitutes being placed on a CHD register and attending an annual check of risk factor man-
agement, usually with a practice nurse.
Co-interventions: not reported
Outcomes HRQL and anxiety and depression (assessed using validated instruments (Seattle Angina Questionnaire
(SAQ) and The MacNew questionnaire))
Notes The exercise was self-directed and documented by participants and not led by clinicians.
Trial was registered with the ISRCTN registry. Registration number: ISRCTN90110503
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence genera- Low risk "A computerized block randomization list was produced by our departmental
tion (selection bias) statistician"

Informed decisions.
Devi 2014 (Continued)
Allocation concealment Low risk "Allocation concealment was achieved by sequentially numbered sealed en-
(selection bias) velopes, opened after baseline data collection for each participant by the re-
searcher carrying out the fieldwork"
Blinding of outcome as- High risk "Participants and the outcome assessor were not blinded to group allocation"
sessment (detection bias)
All outcomes
Incomplete outcome data Low risk All withdrawals and dropouts described, with similar reasons for missing out-
(attrition bias) come data comparable across groups.
All outcomes
10/95 (11% attrition) dropped out at 6 weeks and 21/95 (23% attrition)
dropped out at 6 months
Selective reporting (re- High risk Two intended outcomes (cost and level of positivity) originally reported in the
porting bias) trial protocol were not reported or mentioned in the full report
Groups balanced at base- Low risk Demographic characteristics of both groups were well balanced
line
Groups received compara- High risk Intervention group participants were offered a 6-week web-based rehabilita-
ble care except the inter- tion programme while control group received usual care by GP that set individ-
vention ualized tailored goals focused on exercise (e.g. being physically active for 30
minutes, 5 times a week), diet (e.g. eating more fruit/vegetables and reducing
salt intake), emotions (e.g. managing stress and other negative emotions), and
smoking (e.g. reduce cigarette smoking if relevant).
"The program also contained information to help users understand heart dis-
ease. Program users could initiate contact with cardiac rehabilitation nurses
for advice and support via an online email link or by joining a scheduled syn-
chronized chat room held on a weekly basis."
Not offered to control group.
Hambrecht 2004
No. of centres: 1
Country: Germany
Dates participants recruited: March 1997-March 2001
When randomised: March 1997-March 2001
Participants Inclusion criteria: eligible participants had class I to III angina pectoris (classified according to the
Canadian Cardiovascular Society) with documented myocardial ischaemia during stress ECG and/or
99mTc scintigraphy. Only participants living within a 25 km radius of the host institution were recruit-
ed.
Exclusion criteria: acute coronary syndromes or recent myocardial infarction (< 2 months), left main
coronary artery stenosis > 25% or high-grade proximal left anterior descending artery stenosis, reduced
left ventricular function (ejection fraction < 40%), significant valvular heart disease, insulin-dependent
diabetes mellitus, smoking, and occupational, orthopaedic, and other conditions that precluded regu-
lar exercise. Participants after previous CABG or PCI within the last 12 months were also excluded.
N randomised: total: 101; intervention: 51; comparator: 50

Informed decisions.
Hambrecht 2004 (Continued)


• Previous AMI: intervention: 52%; comparator: 39%
• Previous PCI: not reported
• Previous CABG: not reported
• Acute coronary event: intervention: 52%; comparator: 39%
Age (mean ±SD): total: not reported; intervention: 62±1; comparator: 60±1
Percentage male: 100%

Ethnicity: not reported
Interventions Description: during the first 2 weeks, participants exercised in the hospital 6 times per day for 10 min-
utes on a bicycle ergometer at 70% of the symptom-limited maximal heart rate.
Before discharge from the hospital, a maximal symptom-limited ergospirometry was performed to cal-
culate the target heart rate for home training, which was defined as 70% of the maximal heart rate dur-
ing symptom-limited exercise.
participants were asked to exercise on their bicycle ergometer close to the target heart rate for 20 min-
utes per day and to participate in one 60-minute group training session of aerobic exercise per week.
Components: exercise only
Modality: bicycle ergometer
Dose: 48 x 7 x 20 mins
Length of session: 20 minutes

Frequency: daily
Intensity: not reported
Resistance training included? no
Total duration: 12 months
Intermittent nurse or exercise specialist support? Not reported
Co-interventions: participants recommended to receive acetylsalicyl acid, beta-blockers, an-

giotensin-converting enzyme inhibitors and statins (according to common guidelines)
Comparator:
Description:
The control group all received standard PCI (to target lesion performed 14.8 +/- 3.3 days post randomi-
sation) but no exercise.
Co-interventions:
All participants were given acetylsalicyclic acid (100 mg/d) and clopidogrel (300 mg/d) on the day be-
fore the procedure.
Outcomes Angina symptoms (CCS), exercise capacity, revascularisations, myocardial infarction, cost effective-
ness, combined clinical endpoint (death cardiac, stroke, CABG, PCI, AMI, worsening angina with objec-
tive evidence resulting in hospitalisation)
Notes Source of Funding: unconditional scientific grant from Aventis Germany
Conflicts of Interest: does not declare conflict of interest
Two-year results of this study are reported by Walther 2008.
Risk of bias

Informed decisions.
Hambrecht 2004 (Continued)
Random sequence genera- Unclear risk Unclear if clinician or participant-led treatment allocation: "Patients were ran-
tion (selection bias) domly assigned to either stent angioplasty or exercise training by drawing an
envelope with the treatment assignment enclosed"
Allocation concealment Unclear risk It is unclear if envelopes were sequentially numbered or opaque.
(selection bias)
Blinding of outcome as- Low risk "Initially and after 12 months, the angina pectoris status of all participants
sessment (detection bias) was classified according to CCS class by a physician blinded for patient assign-
All outcomes ment, and a symptom-limited ergospirometry was performed"
Incomplete outcome data Low risk All dropouts and withdrawals were described.
(attrition bias)
All outcomes Intervention: 4/51 lost to follow-up
Control: 3/50 lost to follow-up
No loss to follow-up for primary endpoint analysis
Selective reporting (re- Unclear risk Study protocol was not available
porting bias)
Groups balanced at base- Low risk "Both groups were comparable with regard to baseline characteristics and
line medical therapy (Table 1), which remained unchanged during follow-up"
Groups received compara- Low risk "The control group all received PCI as part of the study however repeat coro-
ble care except the inter- nary angiography was performed to assess the long-term result of the coro-
vention nary intervention in the PCI group and to monitor the progression of athero-
sclerosis in both groups."
Jiang 2007
No. of centres: 1
Country: China
Dates participants recruited: September 2002-December 2003
When randomised: unclear
Participants Inclusion criteria: first hospitalisation with either angina pectoris or myocardial infarction, willing to
participate in this study, able to speak, read and write Chinese, living at home with family after hospital
discharge, living in Chengdu and available for telephone follow-up, and with fasting blood sample tak-
en for lipid test within 24 hours of hospitalisation
Exclusion criteria: planning for surgical treatment; with pre-existing mobility problems; with hypothy-
roidism or nephrotic syndrome; with diagnosed psychosis or currently undergoing anti-psychosis treat-
ment; and with terminal illness
N Randomised: total: 167; intervention: 83; comparator: 84

Informed decisions.
Jiang 2007 (Continued)

• Angina pectoris: intervention: 67.5%; comparator: 69%
• Previous AMI: intervention: 32.5%; comparator: 31%
• Previous PCI: intervention: 33.7%; comparator: 23.8%
• Acute coronary event: intervention: 32.5%; comparator: 30.95%
Age (mean ±SD): total: not reported; intervention: 62.11±97.44; comparator: 61.37±7.61
Percentage male: total: 71.2%; intervention: 68.7%; comparator: 73.8%

Ethnicity: NR
Interventions Description: 12-week home-based cardiac rehabilitation intervention in two phases: hospital-based
patient/family education (topics included physical exercise) and home-based rehabilitation care which
included setting daily behavioural goals for walking performance.
Components: exercise and behaviour change

Modality: walking
Dose: NR
Length of session: NR
Frequency: NR
Intensity: NR
Resistance training included? No
Total duration: 12 weeks
Intermittent nurse or exercise specialist support? Patients were supervised, coached and supported
by an experienced cardiac nurse throughout a 12-week period. Follow-up care was via home visits and
telephone calls.
Co-interventions: education given regarding CHD, medication management, angina prevention and
management, smoking cessation and family support. Family members were encouraged and instruct-
ed to participate in lifestyle change and provide support to patient.
Comparator:
Description: routine care
Co-interventions: none
Outcomes Exercise capacity (Jenkins Activity Checklist for Walking)
Notes Source of funding: The Hong Kong Polytechnic University, Hong Kong, China.
No usable data for our review was measured in this study.
Risk of bias
Random sequence genera- Low risk "Computer-generalized random table"

tion (selection bias)
Allocation concealment Unclear risk Not reported

(selection bias)
Blinding of outcome as- Unclear risk Not reported

All outcomes

Informed decisions.
Jiang 2007 (Continued)
Incomplete outcome data Low risk Intervention: 9/83 (11%) lost to follow-up
(attrition bias)
All outcomes Control: 17/84 (20%) lost to follow-up
Selective reporting (re- Unclear risk No protocol available

porting bias)
Groups balanced at base- Low risk No differences between groups

line
Groups received compara- Unclear risk Intervention received education about a variety of topics (CHD and self-man-
ble care except the inter- agement principles, medication management, angina prevention and man-
vention agement, dietary management, smoking cessation and family support) in ad-
dition to exercise
Manchanda 2000
No. of centres: 1
Country: India
Dates participants recruited: NR
When randomised: NR
Participants Inclusion criteria: have chronic stable angina and angiographically proven CAD
Exclusion criteria: participants with recent (within last six months) myocardial infarction or unstable
angina

• Previous AMI: intervention: 33%; comparator:29%
• Previous CABG: intervention: 10%; comparator:5%
• Acute coronary event: NR
Age (mean ±SD): total: NR; intervention:51±9; comparator:52±10

Interventions Description: yoga lifestyle intervention programme, including yoga exercises, dietary management,
moderate aerobic exercise and stress management.
Participants and their spouses spent 4 days at a yoga residential centre undergoing training in yoga
and various yogic lifestyle techniques. They did yoga exercises at home for 90 mins/day.
Intervention consisted of yogic lifestyle techniques and stress management (health rejuvenation exer-
cises, breathing exercises, relaxation exercises, stretch relaxation, and meditation), dietary control and
moderate aerobic exercises.

Informed decisions.
Manchanda 2000 (Continued)

Components: exercises, psychosocial support and diet advice
Modality: yogic exercises and moderate aerobic exercises
Dose: 48 x 7 x 90 mins
Frequency: daily
Intensity: "moderate"
Resistance training included? NR
Yoga specialist support on a fortnightly basis; going to the hospital for assessment on a monthly basis.
Co-interventions: relaxation, reflection, stress management, diet advice
Comparator:
Description:
Usual care (including medical therapy, risk factor control, diet advice and moderate aerobic exertion)
Co-interventions:
None described
Outcomes All-cause mortality, severity of angina, revascularisation, exercise capacity
Notes Source of Funding: Central Research Institute of Yoga, Ministry of Health, Government of India
Conflicts of Interest: NR
Risk of bias
Random sequence genera- Unclear risk Not reported


(selection bias)
Blinding of outcome as- Unclear risk Not reported

All outcomes
Incomplete outcome data Unclear risk Withdrawals and drop outs not described
(attrition bias)
All outcomes
Selective reporting (re- High risk The study protocol was not available. In the methods section, participants are
porting bias) described as being assessed monthly but only results at 12 months are report-
ed.
Groups balanced at base- High risk Participants in yoga group baseline experienced more angina episodes/week
line
Groups received compara- High risk "The active group was treated with a user-friendly program consisting of yoga,
ble care except the inter- control of risk factors, diet control and moderate aerobic exercise. The con-
vention trol group was managed by conventional methods, i.e. risk factor control and
American Heart Association step I diet."

Informed decisions.
Raffo 1980
No. of centres: 1
Country: not reported
Dates participants recruited: not reported
When randomised: on entry to study
Participants Inclusion criteria: diagnosis of stable angina pectoris
Exclusion criteria: participants with hypertension, valve disease, cardiac arrhythmia, and participants
on digoxin, beta-blocker, or nifedipine therapy

Age (mean ±SD): total: 50; intervention: 51 (not reported); comparator: 49 (not reported)
Percentage male: total: 88%; intervention: 83%; comparator: 92%

Interventions Description: the participants randomised into the training group undertook the Canadian Air Force
programme (5BX/XBX) under supervision in the hospital which required only 11 to 12 minutes of daily
physical training.
The programme lasted six months, and during hospital sessions the participants exercised with elec-
trodes attached in CM5 position.
The participants started training at the lowest physical capacity level, and progressed by increasing
this level according to their age and sex. If the level of exercise was well tolerated the patient was asked
to perform the same level at home during the week and return so that the level could be adjusted un-
der supervision.
If, during the performance of an increased level of exercise, anginal pain and/or ischaemic ST depres-
sion occurred, the participants were maintained at the previous level of exercise.
Components: exercise
Modality: Canadian Air Force Programme
Dose: 24 x 7 x 11
Length of session: 11-12 minutes (daily)
Frequency: daily (at home)
Intensity: training was started at lowest physical capacity level, and progressed by increasing this lev-
el according to age and sex.
Resistance training included? Not reported
Intermittent nurse or exercise specialist support? Not reported
Co-interventions: advice and usual care from consultant cardiologist

Informed decisions.
Raffo 1980 (Continued)

Comparator:
Description: normal daily activities
Co-interventions: advice and usual care from consultant cardiologist
Outcomes Exercise capacity
Notes Sources of Funding: British Heart Foundation and the Wellcome Trust
Conflicts of interest: NR
Risk of bias
Random sequence genera- Unclear risk "On entry to the study, the patients were randomised into two groups." Ran-
tion (selection bias) domisation process not described

(selection bias)
Blinding of outcome as- Low risk Assessment of repeatability of test was blinded: "…HR/ST thresholds obtained
sessment (detection bias) were used for analysis of repeatability of the test, in a blinded fashion as was
All outcomes previously described; all tracings were copied and the five used in the repeata-
bility tests were randomly interspersed by a person other than the observer."
Incomplete outcome data High risk Intervention: 0/12 (0%) lost to follow-up
(attrition bias)
“In the control group an independent decision to start medical treatment with
drugs was made during routine cardiological follow-up on the basis of deterio-
ration of symptoms.”
porting bias)
Groups balanced at base- Unclear risk No significant differences in baseline characteristics however these were only
line data on age, gender and duration of exercise, no other clinical data gathered.
Groups received compara- Low risk “Clinically, the two groups were managed identically by the consultant cardi-
ble care except the inter- ologist (WW). Each patient was advised to stop smoking and avoid increases in
vention body weight.”
Schuler 1992
Methods Study design: RCT (same trial as Niebauer 1995)
No. of centres: 1
Country: Germany
Dates participants recruited: NR
When randomised: after introductory study familiarising participants with aims of study, randomisa-
tion process and alternative therapeutic approaches, and after written consent obtained

Informed decisions.
Schuler 1992 (Continued)

Participants Inclusion criteria: male gender, stable symptoms, willingness to participate in the study for at least 12
months, coronary artery stenoses well documented by angiography, and permanent residence within
25 km of the training facilities at Heidelberg.
Exclusion criteria: unstable angina pectoris, left main coronary artery stenosis > 25% luminal diame-
ter reduction, severely depressed left ventricular function (ejection fraction < 35%), significant valvu-
lar heart disease, insulin-dependent diabetes mellitus, primary hypercholesterolemia (type II hyper-
lipoproteinemia, low density lipoprotein > 210 mg/dl), and occupational, orthopaedic, and other con-
ditions precluding regular participation in exercise sessions
Diagnosis (% of participants): AMI 66%

Age (mean ±SD):
Total: not reported; intervention: 52.8±5.8; comparator: 54.2±7.7

Interventions Description: regular physical exercise and low fat diet (diet advice given during initial 3-week stay on
metabolic ward). Daily exercise at home on a cycle ergometer for a minimum of 20 minutes close to
their target heart rates, which were determined as 75% of the maximal heart rate during symptom-lim-
ited exercise.
In addition, participants were expected to participate in at least two group training sessions consisting
of intensive physical exercise of 60 minutes each week.
Components: exercise, educational and behavioural
Modality: cycle ergometer

Dose: 48 x 7x 30 mins (daily exercise) plus 48 x 2 60 mins (weekly exercise)
Length of session: 30 minutes minimum
Frequency: daily
Intensity: 75% maximal heart rate during symptom-limited exercise
Instructions, given during initial 3 weeks on a metabolic ward, on how to lower the fat content of their
regular diet. Information sessions conducted at regular intervals five times a year for participants and
their spouses to discuss dietary, psychosocial, and exercise-related problems. In addition, participants
were offered opportunities to discuss personal questions and problems after each training session.
Does not state who delivers this. Not performed for control group.
Co-interventions: regular anti-anginal medication (including beta blocking agents), low cholesterol di-
et and advice (as above)
Comparator:

Informed decisions.
Schuler 1992 (Continued)

Description: usual care rendered by private physicians. participants assigned to the control group
spent 1 week on the metabolic ward, where they received identical instructions about the necessity
of regular physical exercise and how to lower fat consumption. They were served a low-fat diet corre-
sponding to the American Heart Association recommendations, phase 1, and they were encouraged to
participate in local coronary exercise groups. Adherence to these guidelines was left to their own initia-
tive
Co-interventions: participants in control group asked not to take lipid lowering medications
Outcomes All-cause mortality, myocardial infarction, revascularisations, exercise capacity, adverse events
Notes Source of funding: grant from Bundesministerium fir Forschung und Technologie, Bonn, FRG.
Risk of bias
Random sequence genera- Unclear risk Process of sequence generation not described
Allocation concealment Unclear risk "Sealed envelopes were used to randomize participants between intervention
(selection bias) and control groups."
Blinding of outcome as- Unclear risk No details of blinding for outcomes were reported.
All outcomes
Incomplete outcome data High risk Intervention: 16/56 (29 %) lost to follow-up
(attrition bias)
porting bias)
Groups balanced at base- Low risk No significant differences in baseline characteristics

line
Groups received compara- High risk "Patients assigned to the control group spent 1 week on the metabolic ward,
ble care except the inter- where they received identical instructions about the necessity of regular phys-
vention ical exercise and how to lower fat consumption. They were served a low-fat
diet corresponding to the American Heart Association recommendations,
phase 1,30 and they were encouraged to participate in local coronary exer-
cise groups. Adherence to these guidelines, however, was left to their own ini-
tiative, and "usual care" was rendered by their private physicians. They were
asked not to take lipid-lowering medications."
In addition to receiving exercise and dietary advice, the intervention group al-
so received regular information sessions "conducted at regular intervals five
times a year for participants and their spouses to
discuss dietary, psychosocial, and exercise-related problems".
Todd 1991
No. of centres: 1
Country: United Kingdom

Informed decisions.
Todd 1991 (Continued)

Dates participants recruited: not reported
When randomised: after study by planar thallium scintigraphy, they were then randomised.
Participants Inclusion criteria: < 60 years old, male, chronic stable angina ≥ 6 months’ duration and a positive exer-
cise tolerance test
Exclusion criteria: previous myocardial infarction, coronary bypass surgery or angioplasty, recent un-
stable angina, diabetes mellitus, uncontrolled hypertension, valvular heart disease and physical handi-
cap

• Previous PCI: intervention: 0%; comparator: 0%
• Previous CABG: intervention: 0%; comparator: 0%
Age (mean ±SD): total: 52; intervention: 53; comparator: 51

Interventions Description: the training group undertook the Canadian Airforce Program for Physical Fitness. This is
a brief 11 -minute daily exercise program of 5 callisthenic exercises requiring no equipment. It was pre-
scribed for daily home use, with exercise levels increasing in intensity at weekly intervals to achieve a
progressive increase in physical fitness. Participants moved to the next level if the previous level could
be completed within 11 minutes without excessive chest pain or dyspnoea. No limit was placed on the
maximum exercise level.
A weekly hospital supervised session was used to initiate new participants and monitor early progress
Components: exercise
Modality: brief "callisthenic exercises"
Dose: 48 x 7 x 11
Frequency: daily
Intensity: increasing intensity with no limit on maximum exercise level
Intermittent nurse or exercise specialist support? Yes
Co-interventions: initial weekly hospital visit for monitoring. Subsequent attendance optional.
Comparator:
Description:
The control subjects were informed that mild exercise may be beneficial and were advised with respect
to diet and smoking habits. They were formally followed up at 3-month intervals throughout the study,
as was the exercise group, but were granted open access to the controlling physician at any time in or-
der to counteract possible bias resulting from weekly contact with the exercise group.
Co-interventions: openly invited to hospital
Outcomes All-cause mortality, myocardial infarction, exercise capacity

Informed decisions.
Todd 1991 (Continued)
Notes
Risk of bias
Random sequence genera- Unclear risk "After thallium scintigraphy, patients were randomly allocated to training and
tion (selection bias) control groups"
No description of randomisation process

(selection bias)
Blinding of outcome as- Unclear risk Blinding not reported

All outcomes
Incomplete outcome data Low risk All withdrawals and drop outs described
(attrition bias)
All outcomes Intervention: 3/20 (15%) lost to follow-up
Control: 4/20 (20%) lost to follow-up
porting bias)
Groups balanced at base- Low risk "There were no significant differences between the groups”
line
Groups received compara- Low risk Control group received advice on exercise, smoking and diet
ble care except the inter-
vention
AMI: acute myocardial infarction

CABG: coronary artery bypass graft
CAD: coronary artery disease
CCS: Canadian Cardiovascular Society
CHD: coronary heart disease
ECG: electrocardiogram
GP: general practitioner
HRQL: health-related quality of life
N: number
NR: not reported
PCI: percutaneous coronary intervention
RCT: randomised controlled trial
SD: standard deviation
Characteristics of excluded studies [ordered by study ID]
Study Reason for exclusion
Back 2008 Participants receive exercise + PCI or no exercise + PCI and so we had concern that co-intervention
(PCI) would confound the comparison.
Byrkjeland 2015 Mixed population—angina population < 50%

Informed decisions.
Study Reason for exclusion
Jiang 2013 Comparator received exercise
Johnson 2009 Mixed population—angina population < 50%
Kay 2000 Comparator received exercise
Linxue 1999 Mixed population—angina population < 50%
Malmborg 1974 Follow-up only 4 months
Menna 1977 Conference abstract - paper not published in full. Unable to contact authors to check for inclusion
due to age of publication.
Michalsen 2006 No structured exercise component
Myers 1987 Population included mixed CHD
Onishi 2010 Mixed population—angina population < 50%
Sullivan 1985 Population did not have angina
Wang 2014 No structured exercise component
Weberg 2013 Mixed population—angina population < 50%
CHD: coronary heart disease

PCI: percutaneous coronary intervention
Characteristics of ongoing studies [ordered by study ID]
NCT00350922
Trial name or title A Clinical Trial of a Self-Management Education Program for People With Chronic Stable Angina
Methods RCT
Participants Adults with chronic stable angina
Interventions Chronic Angina Self-Management Program
Outcomes SF-36; Seattle Angina Questionnaire
Starting date September 2003
Contact information https://clinicaltrials.gov/ct2/show/NCT00350922 (last accessed 01 Sept 2017)
Notes
NCT01147952
Trial name or title The Effect of Exercise on Peripheral Blood Gene Expression in Angina

Informed decisions.
NCT01147952 (Continued)
Methods RCT
Participants Adults with stable angina
Interventions Exercise training
Outcomes Seattle Angina questionnaire (SAQ)
Starting date Not reported
Contact information BMC Public Health 2010;10:620.
Notes
DATA AND ANALYSES
Comparison 1. Exercise versus no exercise for stable angina
Outcome or subgroup title No. of studies No. of partici- Statistical method Effect size
pants
1 All-cause mortality 3 195 Risk Ratio (M-H, Fixed, 95% CI) 1.01 [0.18, 5.67]
2 Acute myocardial infarction 3 254 Risk Ratio (M-H, Fixed, 95% CI) 0.33 [0.07, 1.63]
(AMI)
3 Revascularisation procedure 3 256 Risk Ratio (M-H, Fixed, 95% CI) 0.27 [0.11, 0.64]
(CABG or PCI)
4 Exercise capacity 5 267 Std. Mean Difference (IV, Fixed, 0.45 [0.20, 0.70]
95% CI)
5 Cardiovascular-related hospital 1 101 Risk Ratio (M-H, Fixed, 95% CI) 0.14 [0.02, 1.10]
admissions
Analysis 1.1. Comparison 1 Exercise versus no exercise for stable angina, Outcome 1 All-cause mortality.
Study or subgroup Exercise Control Risk Ratio Weight Risk Ratio
n/N n/N M-H, Fixed, 95% CI M-H, Fixed, 95% CI
Manchanda 2000 0/21 0/21 Not estimable
Todd 1991 0/20 1/20 60.21% 0.33[0.01,7.72]
Schuler 1992 2/56 1/57 39.79% 2.04[0.19,21.82]
Total (95% CI) 97 98 100% 1.01[0.18,5.67]

Total events: 2 (Exercise), 2 (Control)
Heterogeneity: Tau2=0; Chi2=0.81, df=1(P=0.37); I2=0%
Test for overall effect: Z=0.01(P=0.99)
Favours Exercise 0.01 0.1 1 10 100 Favours Control

Informed decisions.
Analysis 1.2. Comparison 1 Exercise versus no exercise for

stable angina, Outcome 2 Acute myocardial infarction (AMI).
Hambrecht 2004 0/51 1/50 25.31% 0.33[0.01,7.84]
Schuler 1992 0/56 3/57 57.98% 0.15[0.01,2.75]
Todd 1991 1/20 1/20 16.71% 1[0.07,14.9]
Total (95% CI) 127 127 100% 0.33[0.07,1.63]

Analysis 1.3. Comparison 1 Exercise versus no exercise for stable

angina, Outcome 3 Revascularisation procedure (CABG or PCI).
Hambrecht 2004 3/51 10/50 45.77% 0.29[0.09,1.01]
Manchanda 2000 1/21 8/21 36.26% 0.13[0.02,0.91]
Schuler 1992 2/56 4/57 17.97% 0.51[0.1,2.67]
Total (95% CI) 128 128 100% 0.27[0.11,0.64]

Test for overall effect: Z=2.95(P=0)
Analysis 1.4. Comparison 1 Exercise versus no exercise for stable angina, Outcome 4 Exercise capacity.
Study or subgroup Exercise Control Std. Mean Difference Weight Std. Mean Difference
N Mean(SD) N Mean(SD) Fixed, 95% CI Fixed, 95% CI
Hambrecht 2004 43 26.2 (5.3) 33 22.8 (5.2) 28.13% 0.65[0.18,1.11]
Manchanda 2000 21 413 (132) 21 374 (151) 16.51% 0.27[-0.34,0.88]
Raffo 1980 12 14.1 (3.3) 5 9.6 (2.5) 4.46% 1.37[0.21,2.54]
Schuler 1992 40 2 (0.4) 52 1.9 (0.5) 35.69% 0.22[-0.2,0.63]
Todd 1991 20 9.7 (2.8) 20 8 (3.1) 15.21% 0.56[-0.07,1.2]
Total *** 136 131 100% 0.45[0.2,0.7]

Heterogeneity: Tau2=0; Chi2=4.77, df=4(P=0.31); I2=16.21%
Test for overall effect: Z=3.57(P=0)
Favours Control -2 -1 0 1 2 Favours Exercise

Informed decisions.
Analysis 1.5. Comparison 1 Exercise versus no exercise for stable

angina, Outcome 5 Cardiovascular-related hospital admissions.
Hambrecht 2004 1/51 7/50 100% 0.14[0.02,1.1]
Total (95% CI) 51 50 100% 0.14[0.02,1.1]

Heterogeneity: Not applicable
APPENDICES
Appendix 1. Search strategy

CENTRAL and DARE
#1 MeSH descriptor: [Angina Pectoris] this term only
#2 MeSH descriptor: [Angina, Unstable] this term only
#3 angina*
#4 stenocardia*
#5 angor pectoris
#6 #1 or #2 or #3 or #4 or #5
#7 MeSH descriptor: [Exercise Therapy] explode all trees
#8 MeSH descriptor: [Sports] this term only
#9 MeSH descriptor: [Physical Exertion] this term only
#10 rehabilitat*
#11 (physical* near/5 (fit* or train* or therap* or activit*))
#12 MeSH descriptor: [Exercise] explode all trees
#13 (train* near/5 (strength* or aerobic* or exercise*))
#14 ((exercise* or fitness) near/3 (treatment or intervent* or program*))
#15 MeSH descriptor: [Rehabilitation] explode all trees
#16 kinesiotherap*
#17 MeSH descriptor: [Physical Education and Training] this term only
#18 MeSH descriptor: [Patient Education as Topic] this term only
#19 (patient* near/5 educat*)
#20 ((lifestyle or life-style) near/5 (interven* or program* or treatment*))
#21 MeSH descriptor: [Self Care] this term only
#22 (self near/5 (manag* or care or motivate*))

Informed decisions.
#23 MeSH descriptor: [Psychotherapy] explode all trees
#24 psychotherap*
#25 (psycholog* near/5 intervent*)
#26 MeSH descriptor: [Counseling] this term only
#27 (counselling or counseling)
#28 ((behavior* or behaviour*) near/5 (modify or modificat* or therap* or change))
#29 (psycho-educat* or psychoeducat*)
#30 (motivat* near/5 (intervention or interv*))
#31 MeSH descriptor: [Health Education] this term only
#32 (health near/5 educat*)
#33 (psychosocial or psycho-social)
#34 (cognitive near/2 behav*)
#35 #7 or #8 or #9 or #10 or #11 or #12 or #13 or #14 or #15 or #16 or #17 or #18 or #19 or #20 or #21 or #22 or #23 or #24 or #25 or #26 or
#27 or #28 or #29 or #30 or #31 or #32 or #33 or #34
#36 #6 and #35
MEDLINE
1 angina pectoris/ or angina, stable/
2 angina.tw.
3 stenocardia*.tw.
4 angor pectoris.tw.
5 1 or 2 or 3 or 4
6 exp Exercise Therapy/
7 Sports/
8 Physical Exertion/
9 rehabilitat*.tw.
10 (physical* adj5 (fit* or train* or therap* or activit*)).tw.
11 exp Exercise/
12 (train* adj5 (strength* or aerobic* or exercise*)).tw.
13 ((exercise* or fitness) adj3 (treatment or intervent* or program*)).tw.
14 exp Rehabilitation/
15 kinesiotherap*.tw.
16 "Physical Education and Training"/
17 Patient Education as Topic/
18 (patient* adj5 educat*).tw.
19 ((lifestyle or life-style) adj5 (interven* or program* or treatment*)).tw.

Informed decisions.
20 Self Care/
21 (self adj5 (manag* or care or motivate*)).tw.
22 exp Psychotherapy/
23 psychotherap*.tw.
24 (psycholog* adj5 intervent*).tw.
25 Counseling/
26 (counselling or counseling).tw.
27 ((behavior* or behaviour*) adj5 (modify or modificat* or therap* or change)).tw.
28 (psycho-educat* or psychoeducat*).tw.
29 (motivat* adj5 (intervention or interv*)).tw.
30 Health Education/
31 (health adj5 educat*).tw.
32 (psychosocial or psycho-social).tw.
33 (cognitive adj2 behav*).tw.
34 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15 or 16 or 17 or 18 or 19 or 20 or 21 or 22 or 23 or 24 or 25 or 26 or 27 or 28 or 29 or
30 or 31 or 32 or 33
35 randomized controlled trial.pt.
36 controlled clinical trial.pt.
37 randomized.ab.
38 placebo.ab.
39 drug therapy.fs.
40 randomly.ab.
41 trial.ab.
42 groups.ab.
43 35 or 36 or 37 or 38 or 39 or 40 or 41 or 42
44 exp animals/ not humans.sh.
45 43 not 44
46 5 and 34 and 45
Embase
1. angina pectoris/ or stable angina pectoris/
2. angina.tw.
3. stenocardia*.tw.
4. angor pectoris.tw.
5. 1 or 2 or 3 or 4
6. exp kinesiotherapy/

Informed decisions.
7. sport/
8. exp exercise/
9. rehabilitat*.tw.
10. (physical* adj5 (fit* or train* or therap* or activit*)).tw.
11. (train* adj5 (strength* or aerobic* or exercise*)).tw.
12. ((exercise* or fitness) adj3 (treatment or intervent* or program*)).tw.
13. kinesiotherap*.tw.
14. exp rehabilitation/
15. physical education/
16. patient education/
17. (patient* adj5 educat*).tw.
18. ((lifestyle or life-style) adj5 (interven* or program* or treatment*)).tw.
19. self care/
20. (self adj5 (manag* or care or motivate*)).tw.
21. exp psychotherapy/
22. psychotherap*.tw.
23. (psycholog* adj5 intervent*).tw.
24. counseling/
25. (counselling or counseling).tw.
26. ((behavior* or behaviour*) adj5 (modify or modificat* or therap* or change)).tw.
27. (psycho-educat* or psychoeducat*).tw.
28. (motivat* adj5 (intervention or interv*)).tw.
29. health education/
30. (health adj5 educat*).tw.
31. (psychosocial or psycho-social).tw.
32. (cognitive adj2 behav*).tw.
33. 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15 or 16 or 17 or 18 or 19 or 20 or 21 or 22 or 23 or 24 or 25 or 26 or 27 or 28 or 29 or 30 or 31 or 32
34. random$.tw.
35. factorial$.tw.
36. crossover$.tw.
37. cross over$.tw.
38. cross-over$.tw.
39. placebo$.tw.
40. (doubl$ adj blind$).tw.
41. (singl$ adj blind$).tw.

Informed decisions.
42. assign$.tw.
43. allocat$.tw.
44. volunteer$.tw.
45. crossover procedure/
46. double blind procedure/
47. randomized controlled trial/
48. single blind procedure/
49. 34 or 35 or 36 or 37 or 38 or 39 or 40 or 41 or 42 or 43 or 44 or 45 or 46 or 47 or 48
50. (animal/ or nonhuman/) not human/
51. 49 not 50
52. 5 and 33 and 51
CINAHL
S46 S5 AND S33 AND S45
S45 S34 OR S35 OR S36 OR S37 OR S38 OR S39 OR S40 OR S41 OR S42 OR S43 OR S44
S44 TX allocat* random*
S43 (MH "Quantitative Studies")
S42 (MH "Placebos")
S41 TX placebo*
S40 TX random* allocat*
S39 (MH "Random Assignment")
S38 TX randomi* control* trial*
S37 TX ( (singl* n1 blind*) or (singl* n1 mask*) ) or TX ( (doubl* n1 blind*) or (doubl* n1 mask*) ) or TX ( (tripl* n1 blind*) or (tripl* n1 mask*) )
or TX ( (trebl* n1 blind*) or (trebl* n1 mask*) )
S36 TX clinic* n1 trial*
S35 PT Clinical trial
S34 (MH "Clinical Trials+")
S33 S6 OR S7 OR S8 OR S9 OR S10 OR S11 OR S12 OR S13 OR S14 OR S15 OR S16 OR S17 OR S18 OR S19 OR S20 OR S21 OR S22 OR S23 OR
S24 OR S25 OR S26 OR S27 OR S28 OR S29 OR S30 OR S31 OR S32
S32 TX (cognitive n2 behav*)
S31 TX (psychosocial or psycho-social)
S30 TX (health n5 educat*)
S29 (MH "Health Education")
S28 TX (motivat* n5 (intervention or interv*))
S27 TX (psycho-educat* or psychoeducat*)
S26 TX ((behavior* or behaviour*) n5 (modify or modificat* or therap* or change))
S25 TX (counselling or counseling)

Informed decisions.
S24 (MH "Counseling")
S23 TX (psycholog* n5 intervent*)
S22 TX psychotherap*
S21 (MH "Psychotherapy+")
S20 TX (self n5 (manag* or care or motivate*))
S19 (MH "Self Care")
S18 TX ((lifestyle or life-style) n5 (interven* or program* or treatment*))
S17 TX (patient* n5 educat*)
S16 (MH "Patient Education")
S15 (MH "Physical Education and Training")
S14 TX kinesiotherap*
S13 TX rehabilitat*
S12 (MH "Rehabilitation+")
S11 TX ((exercise* or fitness) n3 (treatment or intervent* or program*))
S10 TX (train* n5 (strength* or aerobic* or exercise*))
S9 TX (physical* n5 (fit* or train* or therap* or activit*))
S8 (MH "Exercise+")
S7 (MH "Sports")
S6 (MH "Therapeutic Exercise+")
S5 S1 OR S2 OR S3 OR S4
S4 TX angor pectoris
S3 TX stenocardia*
S2 TX angina
S1 (MH "Angina Pectoris") OR (MH "Angina, Unstable")
CPCI-S
#47 AND #46 AND #4
# 47 TS=(random* or blind* or allocat* or assign* or trial* or placebo* or crossover* or cross-over*)
# 46 #45 OR #44 OR #43 OR #42 OR #41 OR #40 OR #39 OR #38 OR #37 OR #36 OR #35 OR #34 OR #33 OR #32 OR #31 OR #30 OR #29 OR
#28 OR #27 OR #26 OR #25 OR #24 OR #23 OR #22 OR #21 OR #20 OR #19 OR #18 OR #17 OR #16 OR #15 OR #14 OR #13 OR #12 OR #11 OR
#10 OR #9 OR #8 OR #7 OR #6 OR #5
# 45 TS=(cognitive NEAR/2 behav*)
# 44 TS=(psychosocial or psycho-social)
# 43 TS=(health NEAR/5 educat*)
# 42 TS=(motivat* NEAR/5 interv*)
# 41 TS=(psycho-educat* or psychoeducat*)
# 40 TS=(behaviour* NEAR/5 change)

Informed decisions.
# 39 TS=(behaviour* NEAR/5 therap*)
# 38 TS=(behaviour* NEAR/5 modificat*)
# 37 TS=(behaviour* NEAR/5 modify)
# 36 TS=(behavior* NEAR/5 change)
# 35 TS=(behavior* NEAR/5 therap*)
# 34 TS=(behavior* NEAR/5 modificat*)
# 33 TS=(behavior* NEAR/5 modify)
# 32 TS=(counselling or counseling)
# 31 TS=(psycholog* NEAR/5 intervent*)
# 30 TS=psychotherap*
# 29 TS=(self NEAR/5 motivate*)
# 28 TS=(self NEAR/5 care)
# 27 TS=(self NEAR/5 manag*)
# 26 TS=(life-style NEAR/5 treatment*)
# 25 TS=(life-style NEAR/5 program*)
# 24 TS=(life-style NEAR/5 interven*)
# 23 TS=(lifestyle NEAR/5 treatment*)
# 22 TS=(lifestyle NEAR/5 program*)
# 21 TS=(lifestyle NEAR/5 interven*)
# 20 TS=(patient* NEAR/5 educat*)
# 19 TS=kinesiotherap*
# 18 TS=(fitness NEAR/3 program*)
# 17 TS=(fitness NEAR/3 intervent*)
# 16 TS=(fitness NEAR/3 treatment)
# 15 TS=(exercise* NEAR/3 program*)
# 14 TS=(exercise* NEAR/3 intervent*)
# 13 TS=(exercise* NEAR/3 treatment)
# 12 TS=(train* NEAR/5 exercise*)
# 11 TS=(train* NEAR/5 aerobic*)
# 10 TS=(train* NEAR/5 strength*)
# 9 TS=(physical* NEAR/5 activit*)
# 8 TS=(physical* NEAR/5 therap*)
# 7 TS=(physical* NEAR/5 train* )
# 6 TS=(physical* NEAR/5 fit*)
# 5 TS=rehabilitat*

Informed decisions.
# 4 #3 OR #2 OR #1
# 3 TS=angor pectoris
# 2 TS=stenocardia*
# 1 TS=angina
WHO's ICTRP
"Cardiac rehabilitation"
rehabilitation AND "angina"
exercise AND "angina"
Clinicaltrials.gov
"Cardiac rehabilitation"
rehabilitation AND angina
exercise AND angina
CONTRIBUTIONS OF AUTHORS
LL contributed to writing the protocol, undertook the 'Risk of bias' assessment, conducted the GRADE analysis and led the writing of the
final review manuscript.
LA led writing of the protocol, undertook study selection and data extraction and contributed to writing the final review manuscript.
AD contributed to writing the protocol and manuscript, undertook study selection, data extraction and 'Risk of bias' assessment, and
approved the final review manuscript.
JH provided clinical expertise, assisted in writing the protocol, undertook study selection, data extraction and 'Risk of bias' assessment.
MG contributed to writing the protocol and provided clinical expertise.
RST led the statistical analysis, conducted the GRADE analysis, edited the review and contributed to writing the final review manuscript.
All authors approved the final review.
DECLARATIONS OF INTEREST
LL declares she has no conflicts of interest.
AD declares she has no conflicts of interest.
JH declares he has no conflicts of interest.
LA is an author on a number of other Cochrane reviews on cardiac rehabilitation (CR).
MG declares she has no conflicts of interest.
RST is an author on a number of other Cochrane reviews on CR and is currently the co-chief investigator on the programme of research
with the overarching aims of developing and evaluating a home-based CR intervention for people with heart failure and their carers (NIHR
PGfAR RP-PG-0611-12004).
SOURCES OF SUPPORT
Internal sources
• University of Exeter Medical School, UK.
External sources
• The Cochrane Heart Group US Satellite is supported by intramural support from the Northwestern University Feinberg School of
Medicine and the Northwestern University Clinical and Translational Science (NUCATS) Institute (UL1TR000150)., USA.

Informed decisions.
• This project was supported by the National Institute for Health Research, via Cochrane Incentive funding to the Heart Group. The views
and opinions expressed therein are those of the authors and do not necessarily reflect those of the Systematic Reviews Programme,
NIHR, NHS or the Department of Health, UK.
DIFFERENCES BETWEEN PROTOCOL AND REVIEW

In addition to the outcomes stated in the protocol, we took the decision to extract data for one additional outcome measure, adverse events
associated with exercise, as we decided that this is an outcome important to patients.
INDEX TERMS
Medical Subject Headings (MeSH)

*Exercise; Angina, Stable [*rehabilitation]; Cardiac Rehabilitation [*methods]; Cause of Death; Hospitalization [statistics & numerical
data]; Myocardial Infarction [epidemiology]; Publication Bias; Quality of Life; Randomized Controlled Trials as Topic
MeSH check words

Aged; Female; Humans; Male; Middle Aged


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Cochrane

Exercise-based cardiac rehabilitation for adults with stable angina

Long L, Anderson L, Dewhirst AM, He J, Bridges C, Gandhi M, Taylor RS

Long L, Anderson L, Dewhirst AM, He J, Bridges C, Gandhi M, Taylor RS.

Exercise-based cardiac rehabilitation for adults with stable angina (Review)

Exercise-based cardiac rehabilitation for adults with stable angina (Review) i

Exercise-based cardiac rehabilitation for adults with stable angina

Editorial group: Cochrane Heart Group.

Data collection and analysis

Exercise-based cardiac rehabilitation for adults with stable angina (Review) 1

PLAIN LANGUAGE SUMMARY

Exercise-based cardiac rehabilitation for people with stable angina

Quality of the evidence

Exercise-based cardiac rehabilitation for adults with stable angina (Review) 2

Patient or population: adults with stable angina

Cochrane Database of Systematic Reviews

Return to work No studies were found that looked at return to work.

GRADE Working Group grades of evidence

Cochrane Database of Systematic Reviews

Exercise-based cardiac rehabilitation for adults with stable angina (Review) 5

Exercise-based cardiac rehabilitation for adults with stable angina (Review) 6

Why it is important to do this review Types of participants

Exercise-based cardiac rehabilitation for adults with stable angina (Review) 7

Exercise-based cardiac rehabilitation for adults with stable angina (Review) 8

Unit of analysis issues 'Summary of findings' table

Exercise-based cardiac rehabilitation for adults with stable angina (Review) 9

Exercise-based cardiac rehabilitation for adults with stable angina (Review) 10

Figure 1. PRISMA flow diagram of trial selection

Exercise-based cardiac rehabilitation for adults with stable angina (Review) 11

Excluded studies Risk of bias in included studies

Exercise-based cardiac rehabilitation for adults with stable angina (Review) 12

Exercise-based cardiac rehabilitation for adults with stable angina (Review) 13

Incomplete outcome data Primary Outcomes

Exercise-based cardiac rehabilitation for adults with stable angina (Review) 14

All-cause hospital admissions concerns about applicability to review question (participants in

Cardiovascular-related hospital admissions DISCUSSION

Exercise-based cardiac rehabilitation for adults with stable angina (Review) 15

Exercise-based cardiac rehabilitation for adults with stable angina (Review) 16

Exercise-based cardiac rehabilitation for adults with stable angina (Review) 17

Exercise-based cardiac rehabilitation for adults with stable angina (Review) 18

Sullivan 1985 {published data only} BHF 2014

References to ongoing studies Clark 2012

Anderson 2016a Egger 1997

Exercise-based cardiac rehabilitation for adults with stable angina (Review) 19

GRADEpro GDT 2015 Lewin 2010

Hambrecht 2000 Montalescot 2013

Hemingway 2006 NACR 2016

Heran 2008a NHLBI 2012

Exercise-based cardiac rehabilitation for adults with stable angina (Review) 20

StataCorp 2013 [Computer program] Taylor 2015

Taylor 2010 Vos 2012

Characteristics of included studies [ordered by study ID]

Country: United Kingdom

Dates participants recruited: September 2008-February 2010

Maximum follow up: 6 months

• Angina pectoris: intervention: 100%; comparator: 100%

Exercise-based cardiac rehabilitation for adults with stable angina (Review) 21

Devi 2014 (Continued)

Percentage male: total: 74%; intervention: 71%; comparator: 78%

Individuals were given tailored goals for exercise.