Exercise for intermittent claudication.

BACKGROUND: Exercise programmes are a relatively inexpensive, low-risk option compared with other, more invasive therapies for treatment of leg pain on walking (intermittent claudication (IC)). This is the fourth update of a review first published in 1998. OBJECTIVES: Our goal was to determine whether an exercise programme was effective in alleviating symptoms and increasing walking treadmill distances and walking times in people with intermittent claudication. Secondary objectives were to determine whether exercise was effective in preventing deterioration of underlying disease, reducing cardiovascular events, and improving quality of life. SEARCH METHODS: For this update, the Cochrane Vascular Information Specialist searched the Specialised Register (last searched 15 November 2016) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 10) via the Cochrane Register of Studies Online, along with trials registries. SELECTION CRITERIA: Randomised controlled trials of an exercise regimen versus control or versus medical therapy for people with IC due to peripheral arterial disease (PAD). We included any exercise programme or regimen used for treatment of IC, such as walking, skipping, and running. Inclusion of trials was not affected by duration, frequency, or intensity of the exercise programme. Outcome measures collected included treadmill walking distance (time to onset of pain or pain-free walking distance and maximum walking time or maximum walking distance), ankle brachial index (ABI), quality of life, morbidity, or amputation; if none of these was reported, we did not include the trial in this review. DATA COLLECTION AND ANALYSIS: For this update (2017), RAL and AH selected trials and extracted data independently. We assessed study quality by using the Cochrane 'Risk of bias' tool. We analysed continuous data by determining mean differences (MDs) and 95% confidence intervals (CIs), and dichotomous data by determining risk ratios (RRs) and 95% CIs. We pooled data using a fixed-effect model unless we identified significant heterogeneity, in which case we used a random-effects model. We used the GRADE approach to assess the overall quality of evidence supporting the outcomes assessed in this review. MAIN RESULTS: We included two new studies in this update and identified additional publications for previously included studies, bringing the total number of studies meeting the inclusion criteria to 32, and involving a total of 1835 participants with stable leg pain. The follow-up period ranged from two weeks to two years. Types of exercise varied from strength training to polestriding and upper or lower limb exercises; supervised sessions were generally held at least twice a week. Most trials used a treadmill walking test for one of the primary outcome measures. The methodological quality of included trials was moderate, mainly owing to absence of relevant information. Most trials were small and included 20 to 49 participants. Twenty-seven trials compared exercise versus usual care or placebo, and the five remaining trials compared exercise versus medication (pentoxifylline, iloprost, antiplatelet agents, and vitamin E) or pneumatic calf compression; we generally excluded people with various medical conditions or other pre-existing limitations to their exercise capacity.Meta-analysis from nine studies with 391 participants showed overall improvement in pain-free walking distance in the exercise group compared with the no exercise group (MD 82.11 m, 95% CI 71.73 to 92.48, P < 0.00001, high-quality evidence). Data also showed benefit from exercise in improved maximum walking distance (MD 120.36 m, 95% CI 50.79 to 189.92, P < 0.0007, high-quality evidence), as revealed by pooling data from 10 studies with 500 participants. Improvements were seen for up to two years.Exercise did not improve the ABI (MD 0.04, 95% CI 0.00 to 0.08, 13 trials, 570 participants, moderate-quality evidence). Limited data were available for the outcomes of mortality and amputation; trials provided no evidence of an effect of exercise, when compared with placebo or usual care, on mortality (RR 0.92, 95% CI 0.39 to 2.17, 5 trials, 540 participants, moderate-quality evidence) or amputation (RR 0.20, 95% CI 0.01 to 4.15, 1 trial, 177 participants, low-quality evidence).Researchers measured quality of life using Short Form (SF)-36 at three and six months. At three months, the domains 'physical function', 'vitality', and 'role physical' improved with exercise; however this was a limited finding, as it was reported by only two trials. At six months, meta-analysis showed improvement in 'physical summary score' (MD 2.15, 95% CI 1.26 to 3.04, P = 0.02, 5 trials, 429 participants, moderate-quality evidence) and in 'mental summary score' (MD 3.76, 95% CI 2.70 to 4.82, P < 0.01, 4 trials, 343 participants, moderate-quality evidence) secondary to exercise. Two trials reported the remaining domains of the SF-36. Data showed improvements secondary to exercise in 'physical function' and 'general health'. The other domains - 'role physical', 'bodily pain', 'vitality', 'social', 'role emotional', and 'mental health' - did not show improvement at six months.Evidence was generally limited in trials comparing exercise versus antiplatelet therapy, pentoxifylline, iloprost, vitamin E, and pneumatic foot and calf compression owing to small numbers of trials and participants.Review authors used GRADE to assess the evidence presented in this review and determined that quality was moderate to high. Although results showed significant heterogeneity between trials, populations and outcomes were comparable overall, with findings relevant to the claudicant population. Results were pooled for large sample sizes - over 300 participants for most outcomes - using reproducible methods. AUTHORS' CONCLUSIONS: High-quality evidence shows that exercise programmes provided important benefit compared with placebo or usual care in improving both pain-free and maximum walking distance in people with leg pain from IC who were considered to be fit for exercise intervention. Exercise did not improve ABI, and we found no evidence of an effect of exercise on amputation or mortality. Exercise may improve quality of life when compared with placebo or usual care. As time has progressed, the trials undertaken have begun to include exercise versus exercise or other modalities; therefore we can include fewer of the new trials in this update.

Tools developed and disseminated by guideline producers to promote the uptake of their guidelines.

BACKGROUND: The uptake of clinical practice guidelines (CPGs) is inconsistent, despite their potential to improve the quality of health care and patient outcomes. Some guideline producers have addressed this problem by developing tools to encourage faster adoption of new guidelines. This review focuses on the effectiveness of tools developed and disseminated by guideline producers to improve the uptake of their CPGs. OBJECTIVES: To evaluate the effectiveness of implementation tools developed and disseminated by guideline producers, which accompany or follow the publication of a CPG, to promote uptake. A secondary objective is to determine which approaches to guideline implementation are most effective. SEARCH METHODS: We searched the Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL); NHS Economic Evaluation Database, HTA Database; MEDLINE and MEDLINE In-Process and other non-indexed citations; Embase; PsycINFO; CINAHL; Dissertations and Theses, ProQuest; Index to Theses; Science Citation Index Expanded, ISI Web of Knowledge; Conference Proceedings Citation Index - Science, ISI Web of Knowledge; Health Management Information Consortium (HMIC), and NHS Evidence up to February 2016. We also searched trials registers, reference lists of included studies and relevant websites. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and cluster-RCTs, controlled before-and-after studies (CBAs) and interrupted time series (ITS) studies evaluating the effects of guideline implementation tools developed by recognised guideline producers to improve the uptake of their own guidelines. The guideline could target any clinical area. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the risk of bias of each included study using the Cochrane 'Risk of bias' criteria. We graded our confidence in the evidence using the approach recommended by the GRADE working group. The clinical conditions targeted and the implementation tools used were too heterogenous to combine data for meta-analysis. We report the median absolute risk difference (ARD) and interquartile range (IQR) for the main outcome of adherence to guidelines. MAIN RESULTS: We included four cluster-RCTs that were conducted in the Netherlands, France, the USA and Canada. These studies evaluated the effects of tools developed by national guideline producers to implement their CPGs. The implementation tools evaluated targeted healthcare professionals; none targeted healthcare organisations or patients.One study used two short educational workshops tailored to barriers. In three studies the intervention consisted of the provision of paper-based educational materials, order forms or reminders, or both. The clinical condition, type of healthcare professional, and behaviour targeted by the CPG varied across studies.Two of the four included studies reported data on healthcare professionals' adherence to guidelines. A guideline tool developed by the producers of a guideline probably leads to increased adherence to the guidelines; median ARD (IQR) was 0.135 (0.115 and 0.159 for the two studies respectively) at an average four-week follow-up (moderate certainty evidence), which indicates a median 13.5% greater adherence to guidelines in the intervention group. Providing healthcare professionals with a tool to improve implementation of a guideline may lead to little or no difference in costs to the health service. AUTHORS' CONCLUSIONS: Implementation tools developed by recognised guideline producers probably lead to improved healthcare professionals' adherence to guidelines in the management of non-specific low back pain and ordering thyroid-function tests. There are limited data on the relative costs of implementing these interventions.There are no studies evaluating the effectiveness of interventions targeting the organisation of care (e.g. benchmarking tools, costing templates, etc.), or for mass media interventions. We could not draw any conclusions about our second objective, the comparative effectiveness of implementation tools, due to the small number of studies, the heterogeneity between interventions, and the clinical conditions that were targeted.

Exercise for intermittent claudication.

BACKGROUND: Exercise programmes are a relatively inexpensive, low-risk option compared with other more invasive therapies for leg pain on walking (intermittent claudication (IC)). This is an update of a review first published in 1998. OBJECTIVES: The prime objective of this review was to determine whether an exercise programme in people with intermittent claudication was effective in alleviating symptoms and increasing walking treadmill distances and walking times. Secondary objectives were to determine whether exercise was effective in preventing deterioration of underlying disease, reducing cardiovascular events and improving quality of life. SEARCH METHODS: For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched September 2013) and CENTRAL (2013, Issue 8). SELECTION CRITERIA: Randomised controlled trials of an exercise regimen versus control or versus medical therapy in people with IC due to peripheral arterial disease. Any exercise programme or regimen used in the treatment of intermittent claudication was included, such as walking, skipping and running. Inclusion of trials was not affected by the duration, frequency or intensity of the exercise programme. Outcome measures collected included treadmill walking distance (time to onset of pain or pain-free walking distance and maximum walking time or maximal walking distance), ankle brachial index (ABI), quality of life, morbidity or amputation; if none of these were reported the trial was not included in this review. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed trial quality. MAIN RESULTS: Eleven additional studies were included in this update making a total of 30 trials which met the inclusion criteria, involving a total of 1816 participants with stable leg pain. The follow-up period ranged from two weeks to two years. The types of exercise varied from strength training to polestriding and upper or lower limb exercises; generally supervised sessions were at least twice a week. Most trials used a treadmill walking test for one of the outcome measures. Quality of the included trials was moderate, mainly due to an absence of relevant information. The majority of trials were small with 20 to 49 participants. Twenty trials compared exercise with usual care or placebo, the remainder of the trials compared exercise to medication (pentoxifylline, iloprost, antiplatelet agents and vitamin E) or pneumatic calf compression; people with various medical conditions or other pre-existing limitations to their exercise capacity were generally excluded.Overall, when taking the first time point reported in each of the studies, exercise significantly improved maximal walking time when compared with usual care or placebo: mean difference (MD) 4.51 minutes (95% confidence interval (CI) 3.11 to 5.92) with an overall improvement in walking ability of approximately 50% to 200%. Walking distances were also significantly improved: pain-free walking distance MD 82.29 metres (95% CI 71.86 to 92.72) and maximum walking distance MD 108.99 metres (95% CI 38.20 to 179.78). Improvements were seen for up to two years, and subgroup analyses were performed at three, six and 12 months where possible. Exercise did not improve the ABI (MD 0.05, 95% CI 0.00 to 0.09). The effect of exercise, when compared with placebo or usual care, was inconclusive on mortality, amputation and peak exercise calf blood flow due to limited data. No data were given on non-fatal cardiovascular events.Quality of life measured using the Short Form (SF)-36 was reported at three and six months. At three months, physical function, vitality and role physical all significantly improved with exercise, however this was a limited finding as this measure was only reported in two trials. At six months five trials reported outcomes of a significantly improved physical summary score and mental summary score secondary to exercise. Only two trials reported improvements in other domains, physical function and general health.Evidence was generally limited for exercise compared with antiplatelet therapy, pentoxifylline, iloprost, vitamin E and pneumatic foot and calf compression due to small numbers of trials and participants. AUTHORS' CONCLUSIONS: Exercise programmes are of significant benefit compared with placebo or usual care in improving walking time and distance in people with leg pain from IC who were considered to be fit for exercise intervention.

Garlic for peripheral arterial occlusive disease.

BACKGROUND: Commercially available preparations of garlic have been reported to have beneficial effects on some of the risk factors associated with atherosclerosis. OBJECTIVES: To assess the effects of garlic (both dried and non-powdered preparations) for the treatment of peripheral arterial occlusive disease. SEARCH METHODS: For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched January 2013) and CENTRAL (2012, Issue 12). SELECTION CRITERIA: Randomised trials of garlic therapy in patients with lower limb atherosclerosis were included. The main outcomes were objective measures of progression of underlying atherosclerosis (e.g. ankle pressure measurements, treadmill testing) and subjective measures (e.g. symptom progression). DATA COLLECTION AND ANALYSIS: Two review authors (RJ and JK) independently extracted data and assessed trial quality. One author (RJ) contacted investigators to obtain information needed for the review that could not be found in published reports. MAIN RESULTS: One eligible trial with 78 participants was found. Both men and women (aged 40 to 75) were included. The follow-up period was short, 12 weeks only.After twelve weeks of treatment, pain-free walking distance increased from 161 to 207 metres in the group receiving garlic and from 172 to 203 metres in the placebo group. This was not a statistically significant difference. There was no difference in change of systolic or diastolic blood pressure, heart rate, ankle and brachial pressures. No severe side effects were observed and nine patients taking garlic (28%) and four patients taking placebo (12%) complained of a noticeable garlic smell.Three trials were excluded from the review because they did not include any clinical measurements. AUTHORS' CONCLUSIONS: One small trial of short duration found no statistically significant effect of garlic on walking distance.

Steroid sex hormones for lower limb atherosclerosis.

BACKGROUND: There is accumulating evidence that steroid sex hormones have a beneficial effect on a number of risk factors for peripheral arterial disease. OBJECTIVES: The objective of this review was to determine whether exogenous steroid sex hormones are an effective treatment for patients with lower limb atherosclerosis. SEARCH METHODS: For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched August 2012) and CENTRAL 2012, Issue 7. There were no language restrictions. SELECTION CRITERIA: We selected randomised or quasi-randomised controlled trials of steroid sex hormones in patients with lower limb atherosclerosis. DATA COLLECTION AND ANALYSIS: Both authors extracted data and assessed trial quality independently. Whenever possible investigators were contacted to obtain information needed for the review that could not be found in published reports. MAIN RESULTS: Four trials appeared to meet the inclusion criteria, but one was excluded because of poor methodology. The three remaining trials compared testosterone treatment with placebo in a total of 109 subjects with intermittent claudication or critical leg ischaemia. The most recent trial to meet the inclusion criteria dated from 1971. No trials were available which investigated the potentially beneficial effects of oestrogenic hormones in women with lower limb atherosclerosis.Testosterone therapy produced no significant improvement in tests of walking distance or in a variety of other objective tests for peripheral arterial disease, including venous filling time, muscle blood flow and plethysmography. The relative risk for subjective improvement in symptoms using the combined trial results was also non-significant (relative risk (RR) 1.10, 95% confidence interval (CI) 0.81 to 1.48). AUTHORS' CONCLUSIONS: There is no evidence to date that short-term testosterone treatment is beneficial in subjects with lower limb atherosclerosis. However, this might reflect limited data rather than the lack of a real effect.

Aspirin for prevention of cardiovascular events in a general population screened for a low ankle brachial index: a randomized controlled trial.

CONTEXT: A low ankle brachial index (ABI) indicates atherosclerosis and an increased risk of cardiovascular and cerebrovascular events. Screening for a low ABI can identify an asymptomatic higher risk group potentially amenable to preventive treatments. OBJECTIVE: To determine the effectiveness of aspirin in preventing events in people with a low ABI identified on screening the general population. DESIGN, SETTING, AND PARTICIPANTS: The Aspirin for Asymptomatic Atherosclerosis trial was an intention-to-treat double-blind randomized controlled trial conducted from April 1998 to October 2008, involving 28,980 men and women aged 50 to 75 years living in central Scotland, free of clinical cardiovascular disease, recruited from a community health registry, and had an ABI screening test. Of those, 3350 with a low ABI (< or = 0.95) were entered into the trial, which was powered to detect a 25% proportional risk reduction in events. INTERVENTIONS: Once daily 100 mg aspirin (enteric coated) or placebo. MAIN OUTCOME MEASURES: The primary end point was a composite of initial fatal or nonfatal coronary event or stroke or revascularization. Two secondary end points were (1) all initial vascular events defined as a composite of a primary end point event or angina, intermittent claudication, or transient ischemic attack; and (2) all-cause mortality. RESULTS: After a mean (SD) follow-up of 8.2 (1.6) years, 357 participants had a primary end point event (13.5 per 1000 person-years, 95% confidence interval [CI], 12.2-15.0). No statistically significant difference was found between groups (13.7 events per 1000 person-years in the aspirin group vs 13.3 in the placebo group; hazard ratio [HR], 1.03; 95% CI, 0.84-1.27). A vascular event comprising the secondary end point occurred in 578 participants (22.8 per 1000 person-years; 95% CI, 21.0-24.8) and no statistically significant difference between groups (22.8 events per 1000 person-years in the aspirin group vs 22.9 in the placebo group; HR, 1.00; 95% CI, 0.85-1.17). There was no significant difference in all-cause mortality between groups (176 vs 186 deaths, respectively; HR, 0.95; 95% CI, 0.77-1.16). An initial event of major hemorrhage requiring admission to hospital occurred in 34 participants (2.5 per 1000 person-years) in the aspirin group and 20 (1.5 per 1000 person-years) in the placebo group (HR, 1.71; 95% CI, 0.99-2.97). CONCLUSION: Among participants without clinical cardiovascular disease, identified with a low ABI based on screening a general population, the administration of aspirin compared with placebo did not result in a significant reduction in vascular events. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN66587262.

Exercise for intermittent claudication.

BACKGROUND: Exercise programmes are a relatively inexpensive, low-risk option compared with other more invasive therapies for leg pain on walking (intermittent claudication (IC)). OBJECTIVES: To determine the effects of exercise programmes on IC, particularly in respect of reduction of symptoms on walking and improvement in quality of life. SEARCH STRATEGY: The Cochrane Peripheral Vascular Diseases Group searched their Specialised Register (last search February 2008) and the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library 2008, Issue 1. SELECTION CRITERIA: Randomised controlled trials of exercise regimens in people with IC due to peripheral arterial disease. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed trial quality. MAIN RESULTS: Twenty-two trials met the inclusion criteria involving a total of 1200 participants with stable leg pain. Follow-up period was from two weeks to two years. There was some variation in the exercise regimens used, all recommended at least two sessions weekly of mostly supervised exercise. All trials used a treadmill walking test for one of the outcome measures. Quality of the included trials was good, though the majority of trials were small with 20 to 49 participants. Fourteen trials compared exercise with usual care or placebo; patients with various medical conditions or other pre-existing limitations to their exercise capacity were generally excluded.Compared with usual care or placebo, exercise significantly improved maximal walking time: mean difference (MD) 5.12 minutes (95% confidence interval (CI) 4.51 to 5.72;) with an overall improvement in walking ability of approximately 50% to 200%; exercise did not affect the ankle brachial pressure index (ABPI) (MD -0.01, 95% CI -0.05 to 0.04). Walking distances were also significantly improved: pain-free walking distance MD 82.19 metres (95% CI 71.73 to 92.65) and maximum walking distance MD 113.20 metres (95% CI 94.96 to 131.43). Improvements were seen for up to two years. The effect of exercise compared with placebo or usual care was inconclusive on mortality, amputation and peak exercise calf blood flow due to limited data.Evidence was generally limited for exercise compared with surgical intervention, angioplasty, antiplatelet therapy, pentoxifylline, iloprost and pneumatic foot and calf compression due to small numbers of trials and participants. Angioplasty may produce greater improvements than exercise in the short term but this effect may not be sustained. AUTHORS' CONCLUSIONS: Exercise programmes were of significant benefit compared with placebo or usual care in improving walking time and distance in selected patients with leg pain from IC.