Improvement In Maximum Walking Distance Research Articles

Network Meta‐Analysis Comparing the Outcomes of Treatments for Intermittent Claudication Tested in Randomized Controlled Trials

BackgroundNo network meta‐analysis has considered the relative efficacy of cilostazol, home exercise therapy, supervised exercise therapy (SET), endovascular revascularization (ER), and ER plus SET (ER+SET) in improving maximum walking distance (MWD) over short‐ (<1 year), moderate‐ (1 to <2 years), and long‐term (≥2 years) follow‐up in people with intermittent claudication.Methods and ResultsA systematic literature search was performed to identify randomized controlled trials testing 1 or more of these 5 treatments according to Preferred Reporting Items for Systematic Review and Meta‐Analysis guidelines. The primary outcome was improvement in MWD assessed by a standardized treadmill test. Secondary outcomes were adverse events and health‐related quality of life. Network meta‐analysis was performed using the gemtc R statistical package. The Cochrane collaborative tool was used to assess risk of bias. Forty‐six trials involving 4256 patients were included. At short‐term follow‐up, home exercise therapy (mean difference [MD], 89.4 m; 95% credible interval [CrI], 20.9–157.7), SET (MD, 186.8 m; 95% CrI, 136.4–237.6), and ER+SET (MD, 326.3 m; 95% CrI, 222.6–430.6), but not ER (MD, 82.5 m; 95% CrI, −2.4 to 168.2) and cilostazol (MD, 71.1 m; 95% CrI, −24.6 to 167.9), significantly improved MWD (in meters) compared with controls. At moderate‐term follow‐up, SET (MD, 201.1; 95% CrI, 89.8–318.3) and ER+SET (MD, 368.5; 95% CrI, 195.3–546.9), but not home exercise therapy (MD, 99.4; 95% CrI, −174.0 to 374.9) or ER (MD, 84.2; 95% CrI, −35.3 to 206.4), significantly improved MWD (in meters) compared to controls. At long‐term follow‐up, none of the tested treatments significantly improved MWD compared to controls. Adverse events and quality of life were reported inconsistently and could not be meta‐analyzed. Risk of bias was low, moderate, and high in 4, 24, and 18 trials respectively.ConclusionsThis network meta‐analysis suggested that SET and ER+SET are effective at improving MWD over the moderate term (<2 year) but not beyond this. Durable treatments for intermittent claudication are needed.

Lower Extremity Intermittent Negative Pressure for Intermittent Claudication. Follow-Up after 24 Weeks of Treatment

Treatment with lower extremity intermittent negative pressure (INP) of -40 mm Hg for one hour twice daily for 12 weeks, increases walking capacity in patients with intermittent claudication (IC). However, the effects of INP treatment beyond 12 weeks have not been elucidated. The aim of the present study was to investigate the clinical effects of INP treatment after 24 weeks in patients with IC. This was a follow-up study after a randomized sham-controlled trial, where patients randomized to the active treatment group were offered to continue treatment for 12 additional weeks (24 weeks in total). Treatment with -40 mm Hg INP was applied in a pressure chamber sealed around the lower leg, and the patients were instructed to treat themselves at home one hour in the morning and one hour in the evening. Pain free walking distance (PWD), maximal walking distance (MWD), resting ankle-brachial index (ABI) and post exercise ABI were measured at baseline, after 12 and 24 weeks. Ten out of 32 patients (31%) from the active treatment group in the initial trial were included in this follow-up study. At baseline, PWD was (mean ±SD) 151 ± 91 m and MWD was 362 ±159 m. There was a significant increase in both PWD and MWD after 24 weeks of treatment, compared to baseline (ANOVA; P= 0.006 and P= 0.012, respectively). Post hoc tests revealed that PWD increased significantly from baseline to 12 weeks (mean 81 m; 95% CI [6, 156]; P = 0.032), and that MWD increased significantly from 12 to 24 weeks (mean 145 m; 95% CI [22, 268]; P = 0.018). There were no significant changes in resting ABI or post exercise ABI during the 24-week treatment period (ANOVA; P= 0.157 and P= 0.450, respectively). Both PWD and MWD improved after treatment with - 40 mm Hg INP for one hour twice daily for 24 weeks, compared to baseline. The main improvement in PWD occurred during the first 12 weeks of treatment, whereas the main improvement in MWD occurred between 12 and 24 weeks of treatment.

The Effect of Arterial Disease Level on Outcomes of Supervised Exercise Therapy for Intermittent Claudication: A Prospective Cohort Study.

To assess whether level of arterial obstruction determines the effectiveness of SET in patients with IC. Guidelines advocate SET before invasive treatment for IC, but early revascularization remains widespread, especially in patients with aortoiliac disease. Patients were recruited from 10 Dutch centers between October 2017 and October 2018. Participants received SET first, followed by endovascular or open revascularization in case of insufficient effect. They were grouped according to level of stenosis (aortoiliac, femoropopliteal, multilevel, or rest group with no significant stenosis). Changes from baseline walking performance (maximal and functional walking distance on a treadmill test, 6-minute walk test) and vascular quality of life questionnaire-6 at 3 and 6 months were compared, after multivariate adjustment for possible confounders. Freedom from revascularization was estimated with Kaplan-Meier analysis. Some 267 patients were eligible for analysis (aortoiliac n = 70, 26%; femoropopliteal n = 115, 43%; multilevel n = 69, 26%; rest n = 13, 5%). No between group differences in walking performance or vascular quality of life questionnaire-6 were found. Mean improvement in maximal walking distance after 6 months was 439 m [99% confidence interval (CI) 297-581], 466 m (99% CI 359-574), 353 m (99% CI 210-496), and 403 m (99% CI 58-749), respectively (P = 0.40). Freedom from intervention was 73.9% for aortoiliac disease and 88.6% for femoropopliteal disease (hazard ratio 2.46, 99% CI 0.96 - 6.30, P = 0.013). Short-term effectiveness of SET for IC is not determined by the location of stenosis. Although aortoiliac disease patients improved walking performance and health-related quality of life similarly compared to other arterial disease level groups, they underwent revascularization more often.

A systematic review of lower extremity electrical stimulation for treatment of walking impairment in peripheral artery disease.

Lower extremity peripheral artery disease (PAD) induces an ischemic pain in the lower limbs and leads to walking impairment. Electrical stimulation has been used in patients with PAD, but no systematic review has been proposed to address the efficacy of the technique as a treatment for walking impairment in PAD. A systematic search was performed to identify trials focused on electrical stimulation for the treatment of walking impairment in patients with PAD in the Cochrane Central Register, PubMed, Embase, and the Web of Science. Studies were included where the primary outcomes were pain-free walking distance and/or maximal walking distance. When appropriate, eligible studies were independently assessed for quality using the Cochrane Collaboration's tool for assessing risk of bias. Five studies eligible for inclusion were identified, of which only two were randomized controlled studies. Trial heterogeneity prevented the use of the GRADE system and the implementation of a meta-analysis. Three types of electrical stimulation have been used: neuromuscular electrical stimulation (NMES, n = 3), transcutaneous electrical stimulation (n = 1), and functional electrical stimulation (n = 1). The two available randomized controlled studies reported a significant improvement in maximal walking distance (+40 m/+34% and +39 m/+35%, respectively) following a program of NMES. Owing to the low number of eligible studies, small sample size, and the risk of bias, no clear clinical indication can be drawn regarding the efficacy of electrical stimulation for the management of impaired walking function in patients with PAD. Future high-quality studies are required to define objectively the effect of electrical stimulation on walking capacity.

Meta-analysis of clinical trials examining the benefit of structured home exercise in patients with peripheral artery disease.

Supervised exercise is recommended for the management of peripheral artery disease (PAD); however, the uptake is limited. Structured home exercise programmes may be more feasible, but their effectiveness is unclear. This systematic review and meta-analysis examined the benefit of structured home exercise programmes for treating PAD in comparison to controls not receiving an exercise programme. A literature search was conducted to identify RCTs comparing structured home exercise with controls not receiving an exercise programme among patients with PAD. To be included, studies had to report outcomes from treadmill or corridor walking tests, or objective assessment of physical activity. Inverse variance-weighted meta-analysis was performed to compare changes in maximum walking distance and intermittent claudication onset distance in treadmill tests, walking distance during a 6-min walking test, and physical activity measured using a pedometer or accelerometer. Summarized results are presented in terms of standard deviation differences. Eleven randomized trials involving 807 patients were included. Follow-up ranged from 2 to 24 months; only one trial included follow-up beyond 12 months. Meta-analyses showed that structured home exercise programmes led to significant improvements in maximum walking distance (mean difference (MD) 0·32, 95 per cent c.i. 0·15 to 0·50; P < 0·001), intermittent claudication onset distance (MD 0·45, 0·27 to 0·62; P < 0·001), walking distance in a 6-min walking test (MD 0·28, 0·09 to 0·47; P = 0·004) and physical activity (MD 0·27, 0·11 to 0·43; P = 0·001). This meta-analysis suggests that structured home exercise programmes are effective at improving walking performance and physical activity in the short term for patients with PAD.

Wearable Sensor Technology Efficacy in Peripheral Vascular Disease (wSTEP): A Randomized Controlled Trial.

To evaluate the effect of using wearable activity monitors (WAMs) in patients with intermittent claudication (IC) within a single-center randomized controlled trial. WAMs allow users to set daily activity targets and monitor their progress. They may offer an alternative treatment to supervised exercise programs (SEPs) for patients with IC. Thirty-seven patients with IC were recruited and randomized into intervention or control group. The intervention consisted of a feedback-enabled, wrist-worn activity monitor (WAM) in addition to access to SEP. The control group was given access to SEP only. The outcome measures were maximum walking distance (MWD), claudication distance (CD), and quality of life as measured by the VascuQol questionnaire. Participants were assessed upon recruitment, and at 3, 6, and 12 months. Patients in the WAM group showed significant improvement in MWD at 3 and 6 months (80-112 m, to 178 m; P < 0.001), which was sustained at 12 months. The WAM group also increased CD (40 vs 110 m; P < 0.001) and VascuQol score (4.7 vs 5.8; P = 0.004). The control group saw a temporary increase in VascuQol score at 6 months (4.5 vs 4.7; P = 0.028), but no other improvements in MWD or CD were observed. Significantly higher improvements in MWD were seen in the WAM group compared with that in the control group at 6 months (82 vs -5 m; P = 0.009, r = 0.47) and 12 months (69 vs 7.5 m; P = 0.011, r = 0.52). The study demonstrates the significant, sustained benefit of WAM-led technologies for patients with IC. This potentially resource-sparing intervention is likely to provide a valuable adjunct or alternative to SEP.

The Improvement of Walking Ability Following Stroke.

Gait velocity and maximum walking distance are central parameters for measuring the success of rehabilitation of gait after a stroke. The goal of this study was to provide an overview of current evidence on the rehabilitation of gait after a stroke. A systematic review of randomized, controlled trials was carried out using network meta-analysis. The primary endpoint was gait velocity; secondary end- points were the ability to walk, maximum walking distance, and gait stability. The following interventions were analyzed: no gait training, conventional gait training (reference category), training on a treadmill with or without body weight support, training on a treadmill with or without a speed paradigm, and electromechanically assisted gait training with end-effector or exoskeleton apparatus. The systematic search yielded 40 567 hits. 95 randomized, controlled trials involving a total of 4458 post-stroke patients were included in the meta-analysis. With respect to the primary endpoint of gait velocity, gait training assisted by end- effector apparatus led to significant improvement (mean difference [MD] = 0.16 m/s; 95% confidence interval [0.04; 0.28]). None of the other interventions improved gait velocity to any significant extent. With respect to one of the secondary endpoints, maximum walking distance, both gait training assisted by end-effector apparatus and treadmill training with body weight support led to significant improvement (MD = 47 m, [4; 90], and MD = 38 m, [4; 72], respectively). A network meta-analysis could not be performed with respect to the ability to walk (a different secondary endpoint) because of substantial inconsistencies in the data. The interventions did not differ significantly with respect to safety. In comparison to conventional gait rehabilitation, gait training assisted by end-effector apparatus leads to a statistically significant and clinically relevant improvement in gait velocity and maximum walking distance after stroke, while treadmill training with body weight support leads to a statistically significant and clinically relevant improvement in maximum walking distance.

Extracorporeal shockwave therapy for intermittent claudication: Medium-term outcomes from a double-blind randomised placebo-controlled pilot trial.

NCT02652078.

Combination of endovascular revascularization and supervised exercise therapy for intermittent claudication: a systematic review and meta-analysis.

Peripheral arterial disease is a major health concern in the Western world, often treated with endovascular revascularization (EVR) or supervised exercise therapy (SET). In this systematic review and meta-analysis, we assessed the outcomes after combination treatment of EVR and SET, compared with EVR or SET alone. We performed a systematic search of Embase, Medline, Web of Science, Cochrane Central and Google Scholar. Only randomized controlled trials comparing combination treatment with EVR or SET only, for patients with intermittent claudication due to femoropopliteal or aortoiliac peripheral artery disease, were included. Primary outcome was maximum walking distance (MWD) at 6 and 12 months' follow-up. Secondary outcomes included pain-free walking distance (PFWD), quality of life and adverse events. Pooled estimates of difference in walking distance between EVR plus SET, EVR only and SET only were calculated using random effects models. Our search yielded 812 articles, of which 7 were finally included in the systematic review. Three studies reported the outcomes of combination treatment versus SET and three more reported the outcomes of combination versus EVR. Follow-up ranged between 6 and 24 months. Combination treatment was associated with a greater MWD at 6 months compared to EVR only or SET only, with a standardized mean difference (SMD) of 0.86 (95% CI: 0.15, 1.57) and 0.41 (95% CI: 0.17, 0.66), respectively. At twelve months no significant difference in maximum walking distance was observed between combination treatment compared to EVR (SMD 0.96 [95% CI: -0.44, 2.37]) or SET (SMD 0.52 [95% CI: -0.17, 1.20]). Compared to EVR only, the combination treatment was associated with a greater PFWD walking distance at 12 months (SMD 0.73 [95% CI 0.01, 1.45]). Most studies reported only minor differences in quality of life in favor of the combination treatment, or no difference at all. Combination treatment of endovascular revascularization followed by SET shows a greater improvement in maximum walking distance at 6 months' follow-up compared to EVR only or SET only, while this difference was no longer present after 12 months.

How Well Do Randomized Controlled Trials Reflect Standard Care: A Comparison between Scientific Research Data and Standard Care Data in Patients with Intermittent Claudication undergoing Supervised Exercise Therapy.

ObjectiveThe aim of the present study was to assess the degree and impact of patient selection of patients with intermittent claudication undergoing supervised exercise therapy in Randomized Controlled Trials (RCTs) by describing commonly used exclusion criteria, and by comparing baseline characteristics and treatment response measured as improvement in maximum walking distance of patients included in RCTs and patients treated in standard care.MethodsWe compared data from RCTs with unselected standard care data. First, we systematically reviewed RCTs that investigated the effect of supervised exercise therapy in patients with intermittent claudication. For each of the RCTs, we extracted and categorized the eligibility criteria and their justifications. To assess whether people in RCTs (n = 1,440) differed from patients treated in daily practice (n = 3,513), in terms of demographics, comorbidity and walking capacity, we assessed between group-differences using t-tests. To assess differences in treatment response, we compared walking distances at three and six months between groups using t-tests. Differences of ≥15% were set as a marker for a clinically relevant difference.ResultsAll 20 included RCTs excluded large segments of patients with intermittent claudication. One-third of the RCTs eligibility criteria were justified. Despite, the numerous eligibility criteria, we found that baseline characteristics were largely comparable. A statistically significant and (borderline) clinically relevant difference in treatment response after three and six months between trial participants and standard care patients was found. Improvements in maximum walking distance after three and six months were significantly and clinically less in trial participants.ConclusionsThe finding that baseline characteristics of patients included in RCTs and patients treated in standard care were comparable, may indicate that RCT eligibility criteria are used implicitly by professionals when referring patients to standard physiotherapy care. The larger treatment response reported in standard physiotherapy care compared to clinical trials, might suggest that scientific studies underestimate the benefits of supervised exercise therapy in patients with intermittent claudication.

Endovascular Revascularization and Supervised Exercise for Peripheral Artery Disease and Intermittent Claudication

Supervised exercise is recommended as a first-line treatment for intermittent claudication. Combination therapy of endovascular revascularization plus supervised exercise may be more promising but few data comparing the 2 therapies are available. To assess the effectiveness of endovascular revascularization plus supervised exercise for intermittent claudication compared with supervised exercise only. Randomized clinical trial of 212 patients allocated to either endovascular revascularization plus supervised exercise or supervised exercise only. Data were collected between May 17, 2010, and February 16, 2013, in the Netherlands at 10 sites. Patients were followed up for 12 months and the data were analyzed according to the intention-to-treat principle. A combination of endovascular revascularization (selective stenting) plus supervised exercise (n = 106) or supervised exercise only (n = 106). The primary end point was the difference in maximum treadmill walking distance at 12 months between the groups. Secondary end points included treadmill pain-free walking distance, vascular quality of life (VascuQol) score (1 [worst outcome] to 7 [best outcome]), and 36-item Short-Form Health Survey (SF-36) domain scores for physical functioning, physical role functioning, bodily pain, and general health perceptions (0 [severe limitation] to 100 [no limitation]). Endovascular revascularization plus supervised exercise (combination therapy) was associated with significantly greater improvement in maximum walking distance (from 264 m to 1501 m for an improvement of 1237 m) compared with the supervised exercise only group (from 285 m to 1240 m for improvement of 955 m) (mean difference between groups, 282 m; 99% CI, 60-505 m) and in pain-free walking distance (from 117 m to 1237 m for an improvement of 1120 m vs from 135 m to 847 m for improvement of 712 m, respectively) (mean difference, 408 m; 99% CI, 195-622 m). Similarly, the combination therapy group demonstrated significantly greater improvement in the disease-specific VascuQol score (1.34 [99% CI, 1.04-1.64] in the combination therapy group vs 0.73 [99% CI, 0.43-1.03] in the exercise group; mean difference, 0.62 [99% CI, 0.20-1.03]) and in the score for the SF-36 physical functioning (22.4 [99% CI, 16.3-28.5] vs 12.6 [99% CI, 6.3-18.9], respectively; mean difference, 9.8 [99% CI, 1.4-18.2]). No significant differences were found for the SF-36 domains of physical role functioning, bodily pain, and general health perceptions. Among patients with intermittent claudication after 1 year of follow-up, a combination therapy of endovascular revascularization followed by supervised exercise resulted in significantly greater improvement in walking distances and health-related quality-of-life scores compared with supervised exercise only. Netherlands Trial Registry Identifier: NTR2249.

Intensive walking exercise for lower extremity peripheral arterial disease: A systematic review and meta-analysis.

Supervised treadmill exercise is the recommended therapy for peripheral arterial disease (PAD) patients with intermittent claudication (IC). However, most PAD patients do not exhibit typical symptoms of IC. The aim of the present study was to explore the efficacy and safety of intensive walking exercise in PAD patients with and without IC. The PubMed, Embase and Cochrane Library databases were systematically searched. Randomized controlled trials comparing the effects of intensive walking exercise with usual care in patients with PAD were included for systematic review and meta-analysis. Eighteen trials with 1200 patients were eligible for the present analysis. Compared with usual care, intensive walking exercise significantly improved the maximal walking distance (MWD), pain-free walking distance, and the 6-min walking distance in patients with PAD (P < 0.00001 for all). Subgroup analyses indicated that a lesser improvement in MWD was observed in the subgroup with more diabetes patients, and that the subgroup with better baseline walking ability exhibited greater improvement in walking performance. In addition, similar improvements in walking performance were observed for exercise programs of different durations and modalities. No significant difference was found in adverse events between the intensive walking and usual care groups (relative risk 0.84; 95% confidence interval 0.51, 1.39; P = 0.50). Regardless of exercise length and modality, regularly intensive walking exercise improves walking ability in PAD patients more than usual care. The presence of diabetes may attenuate the improvements in walking performance in patients with PAD following exercise.

Supervised vs unsupervised exercise for intermittent claudication: A systematic review and meta-analysis

Supervised exercise (SE) is widely accepted as an effective therapy for intermittent claudication (IC), but its use is limited by cost. Unsupervised exercise (UE) represents a less costly alternative. We assessed the comparative effectiveness of SE vs UE in patients with IC. We searched PubMed, EMBASE, and the Cochrane Database of Systematic Reviews and identified 27 unique studies (24 randomized controlled trials, 4 observational studies) that evaluated the comparative effectiveness of SE vs UE in 2074 patients with IC. Compared with UE, SE was associated with a moderate improvement in maximal walking distance at 6 months (effect size 0.77, 95% CI 0.36-1.17, P < .001) and 12 months (effect size 0.56, 95% CI 0.34-0.77, P < .001). Supervised exercise also improved claudication distance to a moderate extent compared with UE at 6 months (effect size 0.63, 95% CI 0.40-0.85, P < .001) and 12 months (effect size 0.41, 95% CI 0.18-0.65, P = .001). There was no difference in the Short Form-36 quality of life at 6 months (effect size -0.05, 95% CI -0.50 to 0.41, P = .84) or walking impairment questionnaire distance (effect size 0.24, 95% CI -0.03 to 0.50, P = .08) or speed (effect size 0.26, 95% CI -0.06 to 0.59, P = .11). In claudication patients, SE is more effective than UE at improving maximal walking and claudication distances, yet there is no difference in general quality of life or patient-reported community-based walking. Further studies are needed to investigate the relationship between functional gain and disease-specific quality of life.

Treatment of hypertension in peripheral arterial disease

Peripheral arterial disease (PAD) causes considerable morbidity and mortality. Hypertension is a risk factor for PAD. Treatment for hypertension must be compatible with the symptoms of PAD. Controversy regarding the effects of beta-adrenoreceptor blockade for hypertension in patients with PAD has led many physicians to stop prescribing beta-adrenoreceptor blockers. Little is known about the effects of other classes of anti-hypertensive drugs in the presence of PAD. This is the second update of a Cochrane review first published in 2003. To determine the effects of anti-hypertensive drugs in patients with both raised blood pressure and symptomatic PAD in terms of the rate of cardiovascular events and death, symptoms of claudication and critical leg ischaemia, and progression of atherosclerotic PAD as measured by ankle brachial index (ABI) changes and the need for revascularisation (reconstructive surgery or angioplasty) or amputation. For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Cochrane Peripheral Vascular Diseases Group Specialised Register (last searched March 2013) and CENTRAL (2013, Issue 2). Randomised controlled trials (RCTs) of at least one anti-hypertensive treatment against placebo or two anti-hypertensive medications against each other, with interventions lasting at least one month. Trials had to include patients with symptomatic PAD. Data were extracted by one author (DAL) and checked by the other (GYHL). Potentially eligible studies were excluded when the results presentation prevented adequate extraction of data and enquiries to authors did not yield raw data. Eight RCTs were included with a total of 3610 PAD patients. Four studies compared a recognised class of anti-hypertensive treatment with placebo and four studies compared two anti-hypertensive treatments with each other. Studies were not pooled due to the variation of the comparisons and the outcomes presented. Overall the quality of the available evidence was unclear, primarily as a result of a lack of detail in the study reports on the randomisation and blinding procedures and incomplete outcome data. Two studies compared angiotensin converting enzyme (ACE) inhibitors against placebo. In one study there was a significant reduction in the number of cardiovascular events in patients receiving ramipril (odds ratio (OR) 0.72, 95% confidence interval (CI) 0.58 to 0.91; n = 1725). In the second trial using perindopril (n = 52) there was a marginal increase in claudication distance but no change in ABI and a reduction in maximum walking distance. A trial comparing the calcium antagonist verapamil versus placebo in patients undergoing angioplasty (n = 96) suggested that verapamil reduced restenosis (per cent diameter stenosis (± SD) 48.0% ± 11.5 versus 69.6% ± 12.2; P < 0.01), although this was not reflected in the maintenance of a high ABI (0.76 ± 0.10 versus 0.72 ± 0.08 for verapamil versus placebo). Another study (n = 80) demonstrated no significant difference in arterial intima-media thickness (IMT) in men receiving the thiazide diuretic hydrochlorothiazide (HCTZ) compared to those receiving the alpha-adrenoreceptor blocker doxazosin (-0.12 ± 0.14 mm and -0.08 ± 0.13 mm, respectively; P = 0.66). A study (n = 36) comparing telmisartan to placebo found a significant improvement in maximum walking distance at 12 months with telmisartan (median (interquartile range (IQR)) 191 m (157 to 226) versus 103 m (76 to 164); P < 0.001) but no differences in ABI (median (IQR) 0.60 (0.60 to 0.77) versus 0.52 (0.48 to 0.67)) or arterial IMT (median (IQR) 0.08 cm (0.07 to 0.09) versus 0.09 cm (0.08 to 0.10)). Two studies compared the beta-adrenoreceptor blocker nebivolol with either the thiazide diuretic HCTZ or with metoprolol. Both studies found no significant differences in intermittent or absolute claudication distance, ABI, or all-cause mortality between the anti-hypertensives. A subgroup analysis of PAD patients (n = 2699) in a study which compared a calcium antagonist-based strategy (verapamil slow release (SR) ± trandolapril) to a beta-adrenoreceptor blocker-based strategy (atenolol ± hydrochlorothiazide) found no significant differences in the composite endpoints of death, non-fatal myocardial infarction or non-fatal stroke with or without revascularisation (OR 0.90, 95% CI 0.76 to 1.07 and OR 0.96, 95% CI 0.82 to 1.13, respectively). Evidence on the use of various anti-hypertensive drugs in people with PAD is poor so that it is unknown whether significant benefits or risks accrue. However, lack of data specifically examining outcomes in PAD patients should not detract from the overwhelming evidence on the benefit of treating hypertension and lowering blood pressure.

Trimetazidine improves exercise performance in patients with peripheral arterial disease

Trimetazidine, an inhibitor of free fatty acids (FFA) oxidation, shifts cardiac and muscle metabolism from FFA to glucose utilization. This effect results in a greater production of high energy phosphates and ultimately into an anti-ischemic effect. Whether the anti-ischemic cardiac effects of trimetazidine (TMZ) can be translated to skeletal muscle in patients with claudication is unknown. We investigated the effectiveness of TMZ on functional performance in patients with peripheral arterial disease (PAD) and claudication. One hundred patients with claudication were enrolled in a parallel, double-blind, 3 months study. Patients were randomized to receive TMZ or matching placebo and were included in a domiciliary exercise program, consisting in daily sessions of aerobic and isotonic exercise for at least five days a week. All patients underwent a treadmill test, evaluating maximal walking distance (MWD), and ankle–brachial index (ABI) at baseline and after 3 months. ABI was similar in the two groups at baseline and did not significantly change at the end of the study in either groups (0.83 + 0.04 vs 0.85 + 0.03, TMZ vs placebo, respectively). MWD improved in all patients with exercise training; however, a greater improvement in MWD was observed with TMZ compared to placebo (23% vs 14%, p < 0.0001). Physical training ameliorates functional performance in PAD. The adjunct of TMZ to exercise induces a greater improvement in MWD, suggesting that the inhibition of FFA oxidation improves functional capacity in patients with PAD and claudication.

PAW25 A single-centre, pilot, randomised controlled trial of recombinant human erythropoietin in primary progressive multiple sclerosis

IntroductionThere is currently no disease modifying therapy for PPMS, which constitutes 10–15% of MS cases. rhEPO is has previously been suggested to have a neuroprotective role in an open label,...

Functional Outcome of Hypogastric Revascularisation for Prevention of Buttock Claudication in Patients with Peripheral Artery Occlusive Disease

We have defined proximal lower limb ischaemia as a decrease in Exercise-transcutaneous oxygen pressure (TcPO 2) lower than minus 15 mmHg at the buttock level in patients with peripheral artery occlusive disease. The purpose of this study was to objectively evaluate the benefits of direct versus indirect revascularisation of internal iliac arteries (IIAs) for prevention of buttock claudication in this population. We retrospectively reviewed the charts of proximal ischaemia patients who underwent revascularisation and both preoperative and postoperative stress TcPO 2 testing. Revascularisation procedures were classified as either direct revascularisation, including percutaneous transluminal angioplasty and internal iliac artery bypass, resulting in a direct inflow in a patent IIA (group 1) or indirect revascularisation, including aortobifemoral bypass and recanalisation of the femoral junction on the ischaemic side, resulting in indirect inflow from collateral arteries in the hypogastric territory (group 2). Patency was checked 3 months after revascularisation in all cases. Treadmill exercise stress tests were performed before and after revascularisation using the same protocol designed to assess pain, determine maximum walking distance (MWD) and measure TcPO 2 during exercise. In addition, ankle–brachial indices (ABIs) were calculated. Between May 2001 and March 2008, a total of 93 patients with objectively documented proximal ischaemia underwent 145 proximal revascularisation procedures using conventional open techniques in 109 cases and endovascular techniques in 36. Direct revascularisation was performed on 50 limbs (35%) (group 1) and indirect revascularisation on 95 limbs (65%) (group 2). The mean interval between revascularisation and stress testing was 60 ± 74 days preoperatively and 149 ± 142 days postoperatively. No postoperative thrombosis was observed. Buttock claudication following revascularisation was more common in group 2 ( p < 0.001). No difference was observed between the two groups with regard to improvement in MWD (365 / 294 m) and ABI (0.20/0.22). Disappearance of proximal ischaemia was more common after direct revascularisation ( p < 0.01). The extent of lesions graded according to the TASC II classification appeared not to be predictive of improvement in assessment criteria following revascularisation. Conversely, patency of the superficial femoral artery was correlated with improvement ( p < 0.01). This study indicates that direct revascularisation, if feasible, provides the best functional outcome for prevention of buttock claudication.

Intermittent Claudication: Exercise-increased Walking Distance is Not Related to Improved Cardiopulmonary Fitness

ObjectivesTo assess if exercise training improves the symptoms of intermittent claudication by improvement in cardiopulmonary fitness. MethodsClaudication distance (CD), maximum walking distance (MWD), calf endurance (repetitive heel raises), cardiovascular fitness (VO2 peak), and ankle-brachial pressure index (ABPI) were measured in 16 subjects with intermittent claudication before, and following an 8-week treadmill training programme. ResultsTraining resulted in a median increase in CD of 65.5m (p<0.01), MWD of 339.5m (p<0.001) and HR of 19 (p<0.03). Notably, improvements in MWD correlated with those in HR (p=0.001; R=0.75). There was no training-associated change in VO2 peak (median increase of only 0.35ml/kg/min; p=0.60) or ABPI (median increase of only 0.01; p=0.64). ConclusionIn this study, overall improvement in claudication was not related to an improvement in cardiopulmonary fitness.

Cost effectiveness of cilostazol compared with naftidrofuryl and pentoxifylline in the treatment of intermittent claudication in the UK

ABSTRACTObjective: To estimate the cost effectiveness of cilostazol (Pletal) compared to naftidrofuryl and pentoxifylline (Trental) in the treatment of intermittent claudication in the UK.* Pletal is a registered trade name of Otsuka America Pharmaceutical, Inc. and marketed in the UK by Otsuka Pharmaceuticals UK, Ltd, London, UK† Trental is a registered trade name of Aventis Phrmaceuticals Inc and marketed in the UK by Aventis Pharma Ltd, Kent, UKDesign and setting: This was a modelling study on the management of patients with intermittent claudication who are 40 years of age or above and have at least six months history of symptomatic intermittent claudication, secondary to lower extremity arterial occlusive disease. The study was performed from the perspective of the UK's National Health Service (NHS).Methods: Clinical outcomes attributable to managing intermittent claudication were obtained from the published literature and resource utilisation estimates were derived from a panel of vascular surgeons. Using decision analytical techniques, a decision model was constructed depicting the management of intermittent claudication with cilostazol, naftidrofuryl and pentoxifylline over 24 weeks in the UK. The model was used to estimate the cost effectiveness (at 2002/2003 prices) of cilostazol relative to the other treatments.Main outcome measures and results: Starting treatment with cilostazol instead of naftidrofuryl is expected to increase the percentage improvement in maximal walking distance by 32% (from 57% to 75%) for a 12% increase in NHS costs (from £801 to £895). Treatment with cilostazol instead of pentoxifylline is expected to increase the percentage improvement in maximal walking distance by 67% (from 45% to 75%) and reduce NHS costs by 2% (from £917 to £895). Treatment with naftidrofuryl instead of pentoxifylline is expected to increase the percentage improvement in maximal walking distance by 27% (from 45% to 57%) and decrease NHS costs by 14% (from £917 to £801).Conclusion: Within the limitations of our model, starting treatment with cilostazol is expected to be a clinically more effective strategy for improving maximal walking distance at 24 weeks than starting treatment with naftidrofuryl or pentoxifylline and potentially the most cost effective strategy. Moreover, the acquisition cost of a drug should not be used as an indication of the cost effectiveness of a given method of care.

Treatment of intermittent claudication with beraprost sodium, an orally active prostaglandin I2analogue: A double-blinded, randomized, controlled trial

ObjectivesIn the current study, we hypothesized that beraprost would: 1) improve treadmill exercise performance and quality of life; and 2) decrease rates of ischemic events in patients with intermittent claudication. BackgroundPrevious trials with beraprost sodium, an orally active prostaglandin I2analogue, in the treatment of claudication in patients with peripheral arterial disease (PAD) have been inconsistent. MethodsPatients with intermittent claudication (n = 897) were randomized to receive either 40 μg three times a day of beraprost with meals (n = 385) or placebo (n = 377) in a double-blinded manner for one year. The primary efficacy parameter was treadmill-measured maximum walking distance, as assessed at three and six months after randomization. Secondary efficacy parameters included treadmill-measured pain-free walking distance and change in quality of life. ResultsThere was no significant improvement in maximum walking distance in the beraprost group (16.7%) as compared with the placebo group (14.6%, p = NS). Administration of beraprost did not improve the pain-free walking distance (p = NS between treatment groups), and there was no improvement in the quality-of-life measures between the treatment groups. The incidence of critical cardiovascular events was 7.3% in the beraprost group and 11.4% in the placebo group (p = NS). There was a significant reduction in the combination of cardiovascular death and myocardial infarction in the beraprost group (p = 0.01). ConclusionsDespite previous investigations suggesting efficacy, these results indicate that beraprost is not an effective treatment to improve symptoms of intermittent claudication in patients with PAD. The potential benefit of beraprost on critical cardiovascular events would require confirmation in a larger prospective investigation.