Lindsey Anderson

Exercise-based cardiac rehabilitation for coronary heart disease

BACKGROUNDnCoronary heart disease (CHD) is the single most common cause of death globally. However, with falling CHD mortality rates, an increasing number of people live with CHD and may need support to manage their symptoms and prognosis. Exercise-based cardiac rehabilitation (CR) aims to improve the health and outcomes of people with CHD. This is an update of a Cochrane systematic review previously published in 2011.nnnOBJECTIVESnTo assess the effectiveness and cost-effectiveness of exercise-based CR (exercise training alone or in combination with psychosocial or educational interventions) compared with usual care on mortality, morbidity and HRQL in patients with CHD.To explore the potential study level predictors of the effectiveness of exercise-based CR in patients with CHD.nnnSEARCH METHODSnWe updated searches from the previous Cochrane review, by searching Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 6, 2014) from December 2009 to July 2014. We also searched MEDLINE (Ovid), EMBASE (Ovid), CINAHL (EBSCO) and Science Citation Index Expanded (December 2009 to July 2014).nnnSELECTION CRITERIAnWe included randomised controlled trials (RCTs) of exercise-based interventions with at least six months follow-up, compared with a no exercise control. The study population comprised men and women of all ages who have had a myocardial infarction (MI), coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI), or who have angina pectoris, or coronary artery disease. We included RCTs that reported at least one of the following outcomes: mortality, MI, revascularisations, hospitalisations, health-related quality of life (HRQL), or costs.nnnDATA COLLECTION AND ANALYSISnTwo review authors independently screened all identified references for inclusion based on the above inclusion and exclusion criteria. One author extracted data from the included trials and assessed their risk of bias; a second review author checked data. We stratified meta-analysis by the duration of follow up of trials, i.e. short-term: 6 to 12 months, medium-term: 13 to 36 months, and long-term: > 3 years.nnnMAIN RESULTSnThis review included 63 trials which randomised 14,486 people with CHD. This latest update identified 16 new trials (3872 participants). The population included predominantly post-MI and post-revascularisation patients and the mean age of patients within the trials ranged from 47.5 to 71.0 years. Women accounted for fewer than 15% of the patients recruited. Overall trial reporting was poor, although there was evidence of an improvement in quality of reporting in more recent trials.As we found no significant difference in the impact of exercise-based CR on clinical outcomes across follow-up, we focused on reporting findings pooled across all trials at their longest follow-up (median 12 months). Exercise-based CR reduced cardiovascular mortality compared with no exercise control (27 trials; risk ratio (RR) 0.74, 95% CI 0.64 to 0.86). There was no reduction in total mortality with CR (47 trials, RR 0.96, 95% CI 0.88 to 1.04). The overall risk of hospital admissions was reduced with CR (15 trials; RR 0.82, 95% CI 0.70 to 0.96) but there was no significant impact on the risk of MI (36 trials; RR 0.90, 95% CI 0.79 to 1.04), CABG (29 trials; RR 0.96, 95% CI 0.80 to 1.16) or PCI (18 trials; RR 0.85, 95% CI 0.70 to 1.04).There was little evidence of statistical heterogeneity across trials for all event outcomes, and there was evidence of small study bias for MI and hospitalisation, but no other outcome. Predictors of clinical outcomes were examined across the longest follow-up of studies using univariate meta-regression. Results show that benefits in outcomes were independent of participants CHD case mix (proportion of patients with MI), type of CR (exercise only vs comprehensive rehabilitation) dose of exercise, length of follow-up, trial publication date, setting (centre vs home-based), study location (continent), sample size or risk of bias.Given the heterogeneity in outcome measures and reporting methods, meta-analysis was not undertaken for HRQL. In five out of 20 trials reporting HRQL using validated measures, there was evidence of significant improvement in most or all of the sub-scales with exercise-based CR compared to control at follow-up. Four trial-based economic evaluation studies indicated exercise-based CR to be a potentially cost-effective use of resources in terms of gain in quality-adjusted life years.The quality of the evidence for outcomes reported in the review was rated using the GRADE method. The quality of the evidence varied widely by outcome and ranged from low to moderate.nnnAUTHORS CONCLUSIONSnThis updated Cochrane review supports the conclusions of the previous version of this review that, compared with no exercise control, exercise-based CR reduces the risk of cardiovascular mortality but not total mortality. We saw a significant reduction in the risk of hospitalisation with CR but not in the risk of MI or revascularisation. We identified further evidence supporting improved HRQL with exercise-based CR. More recent trials were more likely to be well reported and include older and female patients. However, the population studied in this review still consists predominantly of lower risk individuals following MI or revascularisation. Further well conducted RCTs are needed to assess the impact of exercise-based CR in higher risk CHD groups and also those presenting with stable angina. These trials should include validated HRQL outcome measures, explicitly report clinical event outcomes including mortality and hospital admissions, and assess costs and cost-effectiveness.

Exercise-Based Cardiac Rehabilitation for Coronary Heart Disease: Cochrane Systematic Review and Meta-Analysis

BACKGROUNDnAlthough recommended in guidelines for the management of coronary heart disease (CHD), concerns have been raised about the applicability of evidence from existing meta-analyses of exercise-based cardiac rehabilitation (CR).nnnOBJECTIVESnThe goal of this study is to update the Cochrane systematic review and meta-analysis of exercise-based CR for CHD.nnnMETHODSnThe Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, and Science Citation Index Expanded were searched to July 2014. Retrieved papers, systematic reviews, and trial registries were hand-searched. We included randomized controlled trials with at least 6 months of follow-up, comparing CR to no-exercise controls following myocardial infarction or revascularization, or with a diagnosis of angina pectoris or CHD defined by angiography. Two authors screened titles for inclusion, extracted data, and assessed risk of bias. Studies were pooled using random effects meta-analysis, and stratified analyses were undertaken to examine potential treatment effect modifiers.nnnRESULTSnA total of 63 studies with 14,486 participants with median follow-up of 12 months were included. Overall, CR led to a reduction in cardiovascular mortality (relative risk: 0.74; 95% confidence interval: 0.64 to 0.86) and the risk of hospital admissions (relative risk: 0.82; 95% confidence interval: 0.70 to 0.96). There was no significant effect on total mortality, myocardial infarction, or revascularization. The majority of studies (14 of 20) showed higher levels of health-related quality of life in 1 or more domains following exercise-based CR compared with control subjects.nnnCONCLUSIONSnThis study confirms that exercise-based CR reduces cardiovascular mortality and provides important data showing reductions in hospital admissions and improvements in quality of life. These benefits appear to be consistent across patients and intervention types and were independent of study quality, setting, and publication date.

Home-based versus centre-based cardiac rehabilitation

BACKGROUNDnCardiovascular disease is the most common cause of death globally. Traditionally, centre-based cardiac rehabilitation programmes are offered to individuals after cardiac events to aid recovery and prevent further cardiac illness. Home-based cardiac rehabilitation programmes have been introduced in an attempt to widen access and participation. This is an update of a review previously published in 2009 and 2015.nnnOBJECTIVESnTo compare the effect of home-based and supervised centre-based cardiac rehabilitation on mortality and morbidity, exercise-capacity, health-related quality of life, and modifiable cardiac risk factors in patients with heart disease.nnnSEARCH METHODSnWe updated searches from the previous Cochrane Review by searching the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid), Embase (Ovid), PsycINFO (Ovid) and CINAHL (EBSCO) on 21 September 2016. We also searched two clinical trials registers as well as previous systematic reviews and reference lists of included studies. No language restrictions were applied.nnnSELECTION CRITERIAnWe included randomised controlled trials, including parallel group, cross-over or quasi-randomised designs) that compared centre-based cardiac rehabilitation (e.g. hospital, gymnasium, sports centre) with home-based programmes in adults with myocardial infarction, angina, heart failure or who had undergone revascularisation.nnnDATA COLLECTION AND ANALYSISnTwo review authors independently screened all identified references for inclusion based on pre-defined inclusion criteria. Disagreements were resolved through discussion or by involving a third review author. Two authors independently extracted outcome data and study characteristics and assessed risk of bias. Quality of evidence was assessed using GRADE principles and a Summary of findings table was created.nnnMAIN RESULTSnWe included six new studies (624 participants) for this update, which now includes a total of 23 trials that randomised a total of 2890 participants undergoing cardiac rehabilitation. Participants had an acute myocardial infarction, revascularisation or heart failure. A number of studies provided insufficient detail to enable assessment of potential risk of bias, in particular, details of generation and concealment of random allocation sequencing and blinding of outcome assessment were poorly reported.No evidence of a difference was seen between home- and centre-based cardiac rehabilitation in clinical primary outcomes up to 12 months of follow up: total mortality (relative risk (RR) = 1.19, 95% CI 0.65 to 2.16; participants = 1505; studies = 11/comparisons = 13; very low quality evidence), exercise capacity (standardised mean difference (SMD) = -0.13, 95% CI -0.28 to 0.02; participants = 2255; studies = 22/comparisons = 26; low quality evidence), or health-related quality of life up to 24 months (not estimable). Trials were generally of short duration, with only three studies reporting outcomes beyond 12 months (exercise capacity: SMD 0.11, 95% CI -0.01 to 0.23; participants = 1074; studies = 3; moderate quality evidence). However, there was evidence of marginally higher levels of programme completion (RR 1.04, 95% CI 1.00 to 1.08; participants = 2615; studies = 22/comparisons = 26; low quality evidence) by home-based participants.nnnAUTHORS CONCLUSIONSnThis update supports previous conclusions that home- and centre-based forms of cardiac rehabilitation seem to be similarly effective in improving clinical and health-related quality of life outcomes in patients after myocardial infarction or revascularisation, or with heart failure. This finding supports the continued expansion of evidence-based, home-based cardiac rehabilitation programmes. The choice of participating in a more traditional and supervised centre-based programme or a home-based programme may reflect local availability and consider the preference of the individual patient. Further data are needed to determine whether the effects of home- and centre-based cardiac rehabilitation reported in the included short-term trials can be confirmed in the longer term and need to consider adequately powered non-inferiority or equivalence study designs.

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

BACKGROUNDnOverviews are a new approach to summarising evidence and synthesising results from related systematic reviews.nnnOBJECTIVESnTo conduct an overview of Cochrane systematic reviews to provide a contemporary review of the evidence for delivery of cardiac rehabilitation, to identify opportunities for merging or splitting existing Cochrane reviews, and to identify current evidence gaps to inform new cardiac rehabilitation systematic review titles.nnnMETHODSnWe searched The Cochrane Database of Systematic Reviews (2014, Issue 10) to identify systematic reviews that addressed the objectives of this overview. We assessed the quality of included reviews using the Revised Assessment of Multiple Systematic Reviews (R-AMSTAR) measurement tool and the quality of the evidence for reported outcomes using the GRADE framework. The focus of the data presentation was descriptive with detailed tabular presentations of review level and trial level characteristics and results.nnnMAIN RESULTSnWe found six Cochrane systematic reviews and judged them to be of high methodological quality. They included 148 randomised controlled trials (RCTs) in 98,093 participants. Compared with usual care alone, the addition of exercise-based cardiac rehabilitation in low-risk people after myocardial infarction or percutaneous coronary intervention or with heart failure appeared to have no impact on mortality, but did reduce hospital admissions and improved health-related quality of life. Psychological- and education-based interventions alone appeared to have little or no impact on mortality or morbidity but may have improved health-related quality of life. Home- and centre-based programmes were equally effective in improving quality of life outcomes at similar healthcare costs. Selected interventions can increase the uptake of cardiac rehabilitation programmes whilst there is currently only weak evidence to support interventions that improve adherence to cardiac rehabilitation programmes. The quality of the primary RCTs in the included systematic reviews was variable, and limitations in the methodological quality of the RCTs led to downgrading of the quality of the evidence, which varied widely by review and by outcome.nnnAUTHORS CONCLUSIONSnExercise-based cardiac rehabilitation is an effective and safe therapy to be used in the management of clinically stable people following myocardial infarction or percutaneous coronary intervention or who have heart failure. Future RCTs of cardiac rehabilitation need to improve their reporting methods and reflect the real world practice better including the recruitment of higher risk people and consideration of contemporary models of cardiac rehabilitation delivery, and identify effective interventions for enhancing adherence to rehabilitation.

The effectiveness and cost-effectiveness of enzyme and substrate replacement therapies: a longitudinal cohort study of people with lysosomal storage disorders.

OBJECTIVESnTo determine natural history and estimate effectiveness and cost of enzyme replacement therapy (ERT) and substrate replacement therapy (SRT) for patients with Gaucher disease, Fabry disease, mucopolysaccharidosis type I (MPS I), mucopolysaccharidosis type II (MPS II), Pompe disease and Niemann-Pick type C (NPC) disease.nnnDESIGNnCohort study including prospective and retrospective clinical- and patient-reported data. Age- and gender-adjusted treatment effects were estimated using generalised linear mixed models. Treated patients contributed data before and during treatment. Untreated patients contributed natural history data.nnnSETTINGnNational Specialised Commissioning Group-designated lysosomal storage disorder (LSD) treatment centres in England.nnnPARTICIPANTSnConsenting adults and children with a diagnosis of Gaucher disease (n = 272), Fabry disease (n = 499), MPS I (n = 126), MPS II (n = 58), NPC (n = 58) or Pompe disease (n = 93) who had attended a treatment centre in England.nnnINTERVENTIONSnERT and SRT.nnnMAIN OUTCOME MEASURESnClinical outcomes chosen by clinicians to reflect disease progression for each disorder; patient-reported quality-of-life (QoL) data; cost of treatment and patient-reported service-use data; numbers of hospitalisations, outpatient and general practitioner appointments; medication use; data pertaining to associated family/carer costs and QoL impacts.nnnRESULTSnSeven hundred and eleven adults and children were recruited. In those with Gaucher disease (n = 175) ERT was associated with improved platelet count, haemoglobin, liver function and reduced risk of enlarged liver or spleen. No association was found between ERT and QoL. In patients with Fabry disease (n = 311) increased time on ERT was associated with small decreases in left ventricular mass and improved glomerular filtration rate, but not with changes in risk of stroke/transient ischaemic attacks or the need for a hearing aid. There was a statistically significant association between duration of ERT use and worsening QoL and fatigue scores. We found no statistical difference in estimates of treatment effectiveness between the two preparations, agalsidase beta (Fabrazyme(®), Genzyme) (n = 127) and agalsidase alpha (Replagal(®), Shire HGT) (n = 91), licensed for this condition. In Pompe disease (n = 77) our data provide some evidence of a beneficial effect on muscle strength and mobility as measured by a 6-minute walk test in adult-onset patients; there were insufficient data from infantile-onset Pompe patients to estimate associations between ERT and outcome. Among subjects with MPS I (n = 68), 42 of the 43 patients with MPS I subtype Hurlers disease had undergone a bone marrow transplant. No significant associations were found between ERT and any outcome measure for the MPS I subtype Scheie disease and heparan sulphate patients. An association between duration of ERT and growth in children was the only statistically significant finding among patients with MPS II (n = 39). There were insufficient data for patients with NPC disease to draw any conclusions regarding the effectiveness of SRT. The current annual cost to the NHS of the different ERTs means that between 3.6 and 17.9 discounted quality-adjusted life-years (QALYs) for adult patients and between 2.6 and 10.5 discounted QALYs for child patients would need to be generated for each year of being on treatment for ERTs to be considered cost-effective by conventional criteria.nnnCONCLUSIONSnThese data provide further evidence on the effectiveness of ERT in people with LSDs. However, the results need to be interpreted in light of the fact that the data are observational and the relative lack of power due to the small numbers of patients with MPS I, MPS II, Pompe disease and NPC disease. Future work should aim to effectively address the unanswered questions and this will require agreement on a common set of outcome measures and their consistent collection across all treatment centres.nnnFUNDINGnThis project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 16, No. 39. See the HTA programme website for further project information.

Long-term effectiveness of enzyme replacement therapy in Fabry disease: results from the NCS-LSD cohort study

ObjectivesTo determine the effectiveness of enzyme replacement therapy (ERT) for adults and children with Fabry disease.DesignCohort study including prospective and retrospective clinical data. Age- and gender-adjusted treatment effects were estimated using generalised linear mixed models. Treated patients contributed data before and during treatment and untreated patients contributed natural history data.ParticipantsConsenting adults (Nu2009=u2009289) and children (Nu2009=u200922) with a confirmed diagnosis of Fabry disease attending a specialist Lysosomal Storage Disorder treatment centre in England. At recruitment 211 adults and seven children were on ERT (range of treatment duration, 0 to 9.7 and 0 to 4.2xa0years respectively).Outcome measuresClinical outcomes chosen to reflect disease progression included left ventricular mass index (LVMI); proteinuria; estimated glomerular filtration rate (eGFR); pain; hearing and transient ischaemic attacks (TIA)/stroke.ResultsWe found evidence of a statistically significant association between time on ERT and a small linear decrease in LVMI (pu2009=u20090.01); a reduction in the risk of proteinuria after adjusting for angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (pu2009<u20090.001) and a small increase in eGFR in men and women without pre-treatment proteinuria (pu2009=u20090.01 and pu2009<u20090.001 respectively). The same analyses in children provided no statistically significant results. No associations between time on ERT and pain, risk of needing a hearing aid, or risk of stroke or TIAs, were found.ConclusionsThese data provide some further evidence on the long-term effectiveness of ERT in adults with Fabry disease, but evidence of effectiveness could not be demonstrated in children.

Effectiveness of enzyme replacement therapy in adults with late-onset Pompe disease: results from the NCS-LSD cohort study

ObjectivesTo determine the effectiveness of enzyme replacement therapy (ERT) for adults with late-onset Pompe disease.DesignA longitudinal cohort study including prospective and retrospective clinical outcome data. Age- and gender-adjusted treatment effects were estimated using generalised linear mixed models. Treated patients contributed data before and during treatment. Untreated patients contributed natural history data.ParticipantsConsenting adults (Nu2009=u200962) with a diagnosis of late-onset Pompe disease who attended a specialist treatment centre in England. This cohort represented 83xa0% of all patients in the UK with a confirmed diagnosis of this rare condition. At study entry, all but three patients were receiving ERT (range of treatment duration, 0 to 3.1xa0years).Outcome measuresPercent predicted forced vital capacity (%FVC); ventilation dependency; mobility; 6xa0min walk test (6MWT); muscle strength and body mass index (BMI).ResultsAn association was found between time on ERT and significant increases in the distance walked in the 6MWT (pu2009<u20090.001) and muscle strength scores (pu2009<u20090.001). Improvements in both these measures were seen over the first 2xa0years of treatment with ERT. No statistically significant relationship was found between time on ERT and respiratory function or in BMI.ConclusionsThese data provide some further evidence of the effectiveness of ERT in adults with late-onset Pompe disease.SynopsisThe results of this longitudinal cohort study of 62 adults with late-onset Pompe disease, provide further evidence on the effectiveness of ERT in this rare condition.

The NCS-LSD cohort study: a description of the methods and analyses used to assess the long-term effectiveness of enzyme replacement therapy and substrate reduction therapy in patients with lysosomal storage disorders

Lysosomal storage disorders (LSDs) comprise more than 50 extremely rare, inherited metabolic diseases resulting from a deficiency of specific lysosomal enzymes required for normal macromolecular metabolism. The National Collaborative Study for Lysosomal Storage Disorders (NCS-LSD), was a longitudinal cohort study which collected prospective and retrospective clinical data, and patient-reported data from adults and children with a confirmed diagnosis of Gaucher disease, Fabry disease, mucopolysaccharidosis type I (MPS I), mucopolysaccharidosis type II (MPS II), Pompe disease and Niemann Pick disease type C (NPC) in the UK. The study aimed to determine the natural history of these conditions and estimate the effectiveness and cost of therapies. Clinical outcomes were chosen to reflect disease progression. Age- and gender-adjusted treatment effects were estimated using generalised linear mixed models. Treated patients contributed data before and during treatment while untreated patients contributed natural history data. A total of 711 adults and children were recruited to this study from the seven LSD treatment centres in England. Data was collected from 2008 to 2011. This paper describes the methods used to collect and analyse clinical data for this study. The clinical findings are reported separately in a series of condition-specific articles in this issue.

Cochrane corner: cardiac rehabilitation for people with heart disease

Cardiac rehabilitation (CR) has been defined as: ‘the coordinated sum of activities required to influence favourably the underlying cause of cardiovascular disease, as well as to provide the best possible physical, mental and social conditions, so that the patients may, by their own efforts, preserve or resume optimal functioning in their community and through improved health behaviour, slow or reverse progression of disease’.1While exercise training is a cornerstone of CR, it is recommended that ‘comprehensive’ programmes also include education (eg, provision of information about a healthy lifestyle) and psychological intervention (eg, counselling to reduce stress).nnThe first systematic reviews and meta-analyses of CR were published more than 20u2005years ago, and reported a 20%–25% reduction in all-cause and cardiovascular mortality, pooling data from up to 22 randomised trials, comparing exercise-based CR and no-exercise control in over 4300 patients with postmyocardial infarction. In 2001, Jolliffe et al 2 published the first Cochrane review of exercise-based CR, including 32 randomised controlled trials (RCTs) in 8440 patients with postmyocardial infarction and revascularisation. Since then, a further five Cochrane reviews of CR have been published—exercise-based rehabilitation for heart failure, home-based versus centre-based CR, psychological interventions for coronary heart disease, patient education in the management of coronary heart disease and promoting patient uptake and adherence in CR. The portfolio of Cochrane CR review remains dynamic with the publication of regular review updates.nnThe development of this portfolio of Cochrane reviews reflects many of the key areas of evolution in the model provision of CR, and how this model can vary across international healthcare jurisdictions. These include …

Psychological interventions for coronary heart disease: Cochrane systematic review and meta-analysis

Background Although psychological interventions are recommended for the management of coronary heart disease (CHD), there remains considerable uncertainty regarding their effectiveness. Design Systematic review and meta-analysis of randomised controlled trials (RCTs) of psychological interventions for CHD. Methods The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL and PsycINFO were searched to April 2016. Retrieved papers, systematic reviews and trial registries were hand-searched. We included RCTs with at least 6 months of follow-up, comparing the direct effects of psychological interventions to usual care for patients following myocardial infarction or revascularisation or with a diagnosis of angina pectoris or CHD defined by angiography. Two authors screened titles for inclusion, extracted data and assessed risk of bias. Studies were pooled using random effects meta-analysis and meta-regression was used to explore study-level predictors. Results Thirty-five studies with 10,703 participants (median follow-up 12 months) were included. Psychological interventions led to a reduction in cardiovascular mortality (rfcelative risk 0.79, 95% confidence interval [CI] 0.63 to 0.98), although no effects were observed for total mortality, myocardial infarction or revascularisation. Psychological interventions improved depressive symptoms (standardised mean difference [SMD] –0.27, 95% CI –0.39 to –0.15), anxiety (SMD –0.24, 95% CI –0.38 to –0.09) and stress (SMD –0.56, 95% CI –0.88 to –0.24) compared with controls. Conclusions We found that psychological intervention improved psychological symptoms and reduced cardiac mortality for people with CHD. However, there remains considerable uncertainty regarding the magnitude of these effects and the specific techniques most likely to benefit people with different presentations of CHD.