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The effect of exercises on walking distance of patients with intermittent claudication: a study of randomized clinical trials.

BACKGROUND AND PURPOSE: There is no consensus about the indication for exercises for patients with intermittent claudication of the lower extremity and the characteristics of an exercise program to improve walking distance. The effect of walking is assessed by a systematic review of randomized clinical trials. METHODS: Literature databases were accessed using the relevant key words. The references of identified articles were screened for additional studies. A checklist was developed to screen the studies with respect to the variables of interest. A methodological assessment form was developed to assess the methodological quality of the studies (maximum possible score: 100). RESULTS: Eighty-two articles were identified, of which 21 studies were considered relevant for inclusion in the review. Following the analysis of the articles, 11 studies were for various reasons eliminated, leaving 10 studies for the systematic review. The score for methodological quality of the studies ranged from 47 to 75 (mean = 62.5, SD = 8.5). Percentage of improvement in walking distance or time ranged from 28% to 210% (mean = 105%, SD = 55.8%). CONCLUSION AND DISCUSSION: All studies showed that walking exercises improved walking distance in patients with intermittent claudication. Further research is needed to determine the optimal exercise program, the effect of adherence to the treatment protocol, and the duration of the effects following a formal exercise program.

Exercise Therapy↗

Jean-François Bouley (Bouley jeune). Pioneer investigator in intermittent claudication.

Reports of pathologic investigations as to the cause of intermittent claudication in horses were made in France in October, 1831, by veterinarian Jean-François Bouley. Obstructive clots in the femoral arteries were found to be responsible for the muscular changes causing limping. Bouley's work in the horse was used by Charcot in 1858 to understand the mechanism of claudication in the case of a soldier with gunshot wound in whom a traumatic aneurysm, clotting, and ischemia of the legs developed. This was not, however, the first medically reported case of human claudication from vascular occlusive disease; the one reported by Barth in 1835 seems to be the first. According to Dejerine in 1911, the disease in the horse appeared to be due to invasion of the vessels by a parasitic round worm; earlier he had ascribed some cases of human claudication to impaired circulation of the spinal cord. It was not until 1949, however, that Verbiest elaborated the concept of spinal stenosis to explain one type of human claudication.

Animals↗

The effects of acebutolol and metoprolol on walking distances and distal blood pressure in hypertensive patients with intermittent claudication.

The effects of acebutolol (with intrinsic sympathomimetic activity (ISA] and metoprolol (without ISA) on arm blood pressure, ankle systolic blood pressure, claudication distances (CD) and maximal walking distances (MWD) were compared in patients with essential hypertension and intermittent claudication. Fourteen patients participated in a long-term, open, randomized cross-over study. After randomization the patients received either acebutolol, 200 mg b.i.d., or metoprolol, 100 mg b.i.d. After eight weeks the drugs were shifted and after another eight weeks they were withdrawn. Arm and ankle blood pressure, CD and MWD were determined before randomization and after 4, 8, 12 and 16 weeks, and again 4-6 weeks after withdrawal of the drugs. The arm blood pressure was reduced by 20/13 mmHg after acebutolol and by 22/21 mmHg after metoprolol. In spite of a significant decrease in arm blood pressure there were no significant changes in ankle blood pressure, CD or MWD after the two drugs. After withdrawal of the drugs and after the arm blood pressure had returned to the control value no significant changes were seen in CD, MWD or ankle blood pressure. It is concluded that beta-blockers have no deleterious effect on CD, MWD or ankle blood pressure in patients with hypertension and intermittent claudication. No effect of ISA was demonstrated.

Acebutolol↗

A new functional test in the diagnostic evaluation of neurogenic intermittent claudication.

A new functional test using downhill walking is described and evaluated in relation to the myelographical examination in 23 consecutive patients with neurogenic intermittent claudication. Discomfort and changes of the neurological status, emerging during the walk, were accepted as test results. They were noted in a decision matrix and the positive and the negative predictive values (PPV and NPV, respectively) calculated. The PPV of any symptom or any deterioration of the neurological status, resulting from this test as signs of a myelographical abnormality, was calculated to be 86 and 89 per cent, respectively, the corresponding NPV's being 50 and 40 per cent, respectively. The NPV of these parameters as signs of a myelographically verified lumbar spinal stenosis was calculated to be 100 per cent, the corresponding PPV's being 38 and 44 per cent, respectively. The development of "symptom-march" or of bilateral neurological signs during the walk was found to be of approximately the same diagnostical value. We conclude, that this function test may serve as a screening procedure in patients complaining of neurogenic intermittent claudication.

Adult↗

Effect of treadmill exercise on blood gases and acid-base balance in patients with intermittent claudication.

Blood gases and lactate and pyruvate concentration were measured in arterial and popliteal venous blood in 6 control subjects and 34 patients with intermittent claudication before, during, and after treadmill exercise of 10 min duration. Oxygen saturation, oxygen extraction, base excess, and standard bicarbonate were calculated. The transition from resting supine position to upright position on the treadmill caused the popliteal venous oxygen saturation to fall from 49.4% to 26.3%. In patients, during exercise a further decrease (to 11%) was observed. During treadmill exercise the popliteal venous PO2 did not fall below 16.5 +/- 1.1 mm Hg in the controls. Individual values during exercise varied between 6.4 mm Hg and 17.9 mm Hg in patients. A critical oxygen pressure was reached in 10 patients. Lactate concentration was found to increase to values as high as 14 mmol/l in popliteal venous blood. The lactate-pyruvate ratio varied between 12.9 and 106.3 during exercise, and the corresponding values for venous blood pH were 7.38 and 6.92. Changes in the PCO2, lactate, and pH in arterial and popliteal venous blood showed a significant correlation. The decrease in the base excess was greater than the corresponding increase in the blood lactate concentration. It is concluded that analysis of the acid-base balance in patients with intermittent claudication is best carried out by the regional catheterization technique.

Acid-Base Equilibrium↗

Clinical and hemodynamic effects of stepwise lowering of hemoglobin concentration in patients with intermittent claudication.

This study evaluates the effect of stepwise lowering of the hemoglobin (Hb) concentration on maximal walking distance (MWD) and hemodynamics in patients with intermittent claudication. The results in a study group (n = 6) were compared with those of a control group (n = 6) whose members were not subjected to venesections. An average decrease of Hb concentration from 151 +/- 4 to 121 +/- 3 g/L did not significantly influence MWD, the result being 282 +/- 62 meters before venesections and 255 +/- 54 meters after three to five (mean four) repeated venesections. Transcutaneous oxygen pressure was measured at the dorsum of the foot before and after exercise and did not change with a gradual decrease of the Hb concentration. Maximal heart rate, painfree walking distance, ankle pressure, and blood lactate concentration were also unchanged. An average venesection volume of about 1.4 liters whole blood within fourteen days, without isovolemic replacement, did not change the blood volume, which was 5.1 +/- 0.4 liters before and 5.0 +/- 0.5 liters after venesections. In conclusion, hemodilution accomplished by venesections did not have a clinically or physiologically beneficial effect in patients with severe intermittent claudication. However, hemodynamics and clinical symptoms were not affected by a considerable decrease in the arterial oxygen content within the normal Hb concentration range.

Aged↗

Cessation of smoking in patients with intermittent claudication. Effects on the risk of peripheral vascular complications, myocardial infarction and mortality.

The effects of cessation of smoking were studied in 343 patients with intermittent claudication. One year after the initial examination 39 (11%) had stopped smoking and 304 (89%) continued to smoke. The outcome in these two groups was compared. They were comparable regarding baseline characteristics. Rest pain did not develop in any of the non-smokers. In smokers the cumulative proportion with rest pain was 16% after seven years (p less than 0.05). The cumulative proportions with myocardial infarctions after 10 years were 11 and 53%; the cumulative rates of cardiac deaths 6 and 43%; and the 10-year survival 82 and 46% among non-smokers and smokers, respectively. In multivariate Cox regression analyses the association between smoking and infarction (p less than 0.05) and cardiac death (p less than 0.05) was significant. The survival curves deviated and when they were compared after one year's follow-up the association between smoking and mortality was significant (p less than 0.05). The findings provide further evidence for the fact that it is of utmost importance that patients with intermittent claudication stop smoking.

Aged↗

Effect of simvastatin versus placebo on treadmill exercise time until the onset of intermittent claudication in older patients with peripheral arterial disease at six months and at one year after treatment.

Simvastatin significantly increased treadmill exercise time until onset of intermittent claudication from baseline by 54 seconds (a 24% increase, p <0.0001) at 6 months after treatment and by 95 seconds (a 42% increase, p <0.0001) at 1 year after treatment. At 6 months and 1 year after treatment with placebo, treadmill exercise time until onset of intermittent claudication was not significantly different from baseline exercise time.

Aged↗

[Comparison of the effectiveness of intra-arterial and intravenous administration of buflomedil in patients with intermittent claudication].

Buflomedil is a vasoactive agent widely used in the treatment of peripheral arterial disease. 42 patients with peripheral obliterative arterial disease (POAD) in the intermittent claudication stage were treated in a randomized controlled study with 200 mg Buflomedil either intraarterially or intravenously. The infusions with this vasoactive agent were given daily for 15 days, on weekends the patients took 300 mg Buflomedil orally twice. Painfree walking distance on a treadmill was below 75 m at entrance. The treatment was controlled by treadmill test and systolic blood pressure gradients. The painfree walking distance was improved in the i.v. group from 38.7 to 91.7 m (+137%); in the i.a. group from 43.4 to 126m (+190%). There was a significant difference between the increases of painfree walking distances in both groups. No changes of doppler gradients occured. The result of this controlled study confirm that i.a. administered Buflomedil increases painfree walking distances more pronounced than i.v. infusions in patients with intermittent claudication due to POAD.

Clinical Trials as Topic↗

[Neurogenic intermittent claudication].

In the period 1971-1981 operations were carried out in 1114 cases of discopathy or lumbar spondylosis. Three patients in this group had pains of the type of intermittent claudication as the main symptoms. In all these cases narrowing of the vertebral canal was found in the lumbar part caused in two cases by degenerative changes and herniation of the intervertebral discs, and in a third case it was due to an extensive connective tissue scar at the site of previously done laminectomy. The nerve roots of the cauda were relieved from pressure surgically and in all cases pains disappeared. The authors discuss factors contributing to the development of neurogenic intermittent claudication.

Adult↗

Treatment of intermittent claudication with mesoglycan--a placebo-controlled, double-blind study.

OBJECTIVE: To assess the effect of treatment with mesoglycan, a sulphated polysaccharide compound, on the walking capacity of patients with stage II peripheral arterial disease. METHODS: Non-diabetic outpatients with intermittent claudication, duplex ultrasound evidence of peripheral atherosclerosis, ankle/arm index <0.80, systolic ankle pressure >50 mmHg, and absolute walking distance (AWD) between 100 and 300 m (standardised treadmill test) were eligible. After a 5-week run-in on single-blind placebo, patients were randomised to double-blind treatment with mesoglycan, 30 mg/day intramuscularly for 3 weeks followed by 100 mg/day orally for 20 weeks, or matching placebo. All patients received low-dose aspirin and lifestyle instructions. Clinical response was defined as an AWD increase at Week 23 >50% over baseline. Health-related quality of life and ischaemic events were assessed as secondary efficacy variables. RESULTS: 242 patients were randomised and 237 were assessed for clinical response. Patients achieving clinical response were 59/118 with mesoglycan (50.0%) and 31/119 with placebo (26.1%; p <0.001). Geometric mean AWD increased from 192 to 298 m with mesoglycan, and from 192 to 238 m with placebo (p <0.001). Pain-free walking distance showed a non-significant increase with mesoglycan (p = 0.057). Changes in quality of life scores were in favour of mesoglycan. The rate of ischaemic events was 1/120 on mesoglycan and 6/122 on placebo (p = 0.053). The rate of non-ischaemic adverse events leading to treatment discontinuation was 7/120 and 4/122, respectively. CONCLUSION: Treatment with mesoglycan improves the walking capacity of patients with intermittent claudication, and might confer additional antithrombotic protection over that of aspirin.

Aged↗

Above-knee prosthetic femoropopliteal bypass for intermittent claudication. Results of the initial and secondary procedures.

OBJECTIVES: [corrected] to report the results of primary and secondary prosthetic above-knee femoropopliteal bypass for intermittent claudication. DESIGN: a retrospective study in a University hospital. PATIENTS: one hundred and twelve operations performed in 103 patients (26 women) between January 1990 and June 1997. METHODS: a comparison of primary assisted patency was made between Dacron and PTFE, between men and women and between operations performed early and late in the study period. Patency of secondary procedures was also studied. RESULTS: there were no operative deaths. The 5-year survival rate was 81% and equal to that of a demographically matched population. The primary assisted graft patency was 58% after two years. Women had a significantly better graft patency than men (79% vs. 49%). The type of graft and the date of the operation did not influence the outcome. Forty of the 55 occluded grafts were subjected to a redo procedure with a 1-year patency of 29%. CONCLUSIONS: the results after prosthetic above-knee femoropopliteal bypass procedures are disappointing, and a controversy persists as to whether this operation should be performed for intermittent claudication. The results of secondary procedures are even worse, and perhaps should only be considered in patients suffering critical ischaemia.

Adult↗

Delayed respiratory response to exercise of short duration in patients with severe intermittent claudication due to bilateral atherosclerotic vascular disease: normalization after aorto-bifemoral bypass operation.

To investigate the respiratory response to exercise in patients with severe intermittent claudication, eight male patients, aged 57 years (range 43-73), with bilateral multi-segment atherosclerotic vascular disease, median maximum walking distance 50 m (range 20-200) and ankle-to-arm pressure index 0.4 (range 0.3-0.6), were studied before and after aorto-bifemoral bypass operation. Ventilation, CO2 output and O2 intake were recorded in the sitting position during 20 min of rest, 1 min of leg exercise on a bicycle ergometer [4.9 kJ (500 kpm)], and 20 min of recovery and rest. Before operation, maximal ventilation and CO2 output per minute were observed 2-4 min after cessation of work, while afterwards peak values were found during the work or the first minute of recovery. Pre-operatively, the extra ventilation and CO2 output during the work and recovery period and the recovery times of the ventilation and CO2 output per minute were markedly increased. Afterwards these values were clearly reduced towards normal. It is concluded that patients with severe intermittent claudication show a characteristic delay and prolonged rise in the respiratory response to exercise of short duration, which closely corresponds to the previously described pattern of outflow of hypoxia-generated metabolites from the exercising muscles. The pattern of respiratory response after operation reflects the fact that these patients also suffer from atherosclerotic heart dysfunction.

Adult↗

Medical treatment in intermittent claudication.

A variety of measures advocated in the treatment of intermittent claudication are critically reviewed. Daily leg exercises increase the walking ability but the mechanism of this effect remains controversial. To date, doubt persists whether drugs, either vasodilating or antithrombotic, are of any clinical value in this condition.

Exercise Therapy↗

The systemic effects of intermittent claudication are reversed by angioplasty.

INTRODUCTION: exercise in patients with intermittent claudication causes systemic effects, the consequences of which are unknown. This study investigates whether successful PTA reverses the systemic effects. PATIENTS AND METHODS: ten patients with IC were recruited prior to PTA. Having emptied their bladders and rested for 1 h, pre-exercise blood and urine samples were collected. Patients underwent treadmill exercise to maximum walking time and blood samples were collected at 10, 20 and 30 min. A second urine sample was collected at 60 min. Total antioxidant capacity (TAC) and von Willebrands Factor (vWF) were measured in blood and albumin/creatinine ratio (ACR) and retinol binding protein/creatinine ratio (RBP/Cr) in urine. Patients were recalled 2 weeks after successful angioplasty and the protocol repeated. Following PTA patients walked for a maximum of 5 min. RESULTS: there was no significant change in vWF. Exercise in claudicants induced a significant increase in median ACR (pre/post exercise=0.85 p =0.03) and in median RBP/Cr (pre/post exercise=1.8 p =0.04). These changes were no longer evident after successful PTA. TAC was significantly different before and after angioplasty at all time intervals. CONCLUSION: successful PTA reverses glomerular effects of exercise in claudicants. Future work should investigate the use of PTA in conjunction with exercise in the treatment of peripheral vascular disease.

Adult↗

The effects of physical training and flunarizine on walking capacity in intermittent claudication.

The clinical significance of drugs improving red cell deformability is not confirmed. We established the effect of physical training alone and combined with flunarizine on intermittent claudication. Twelve patients aged 48-73 years were included in the study. Pain-free walking distance on treadmill, ankle/arm pressure ratio and transcutaneous oxygen tension were measured. Walking distance increased significantly (p less than 0.05) by 130% from 75 m to 173 m during the first year when the patients were on programmed physical training. Ankle/arm pressure ratio also increased significantly (p less than 0.05) from 0.46 to 0.55 during this period. The increase in walking distance ceased when the programmed physical training was discontinued for 6 months. During the following double-blind, cross-over medication period the patients were given flunarizine 5 mg b.i.d. and placebos in randomized order for 3 months each. They also continued the same programmed physical training as during the first year. Walking distance increased, albeit not significantly, with time to 392 m after the second medication period. There was no difference, however, between flunarizine and placebo. Ankle/arm pressure ratio was of the same magnitude as at the beginning of the trial. Oxygen tension measurements did not give consistent results. We conclude that programmed physical training increased walking distance as a function of time. Flunarizine had no effect on the performance of patients with intermittent claudication.

Aged↗

Intermittent claudication incites systemic neutrophil activation and increased vascular permeability.

Reperfusion following severe ischaemia incites a systemic response involving neutrophil activation and vascular injury. Recent work suggests that intermittent claudication may also be capable of inducing similar changes, reversible by revascularization. This observation may have implications for the treatment of claudication and explain the high associated cardiovascular mortality. This hypothesis was investigated using an in vivo model. Rats underwent repeated hindlimb stimulation after common iliac artery ligation. Intravital fluorescence microscopy was used to observe postcapillary venules of the tibialis anterior muscle in the hindlimb. This revealed a bilateral increase in leucocyte-endothelial adhesion and vascular permeability to albumin after unilateral subtotal ischaemia and muscle stimulation, associated with increased urinary albumin excretion. These results provide further evidence supporting the association of intermittent claudication with potentially deleterious systemic manifestations.

Animals↗

A double-blind, placebo-controlled study of the effects of policosanol in patients with intermittent claudication.

This study was undertaken to evaluate the efficacy and tolerability of policosanol, a new cholesterol-lowering drug with concomitant antiplatelet effects, in patients with intermittent claudication. After a baseline period of 6 weeks, 62 patients were randomized to receive, under double-blind conditions, either placebo (31 patients) or policosanol (31), 10 mg twice daily. Walking distances in a treadmill (constant speed 3.2 km/hr, slope 10 degrees) were assessed before and after 6 months of treatment. Both groups were similar at randomization. Policosanol increased significantly (p < 0.01) the initial claudication distance from 132.5+/-13.5 m (baseline) to 205.7+/-36.3 m (after therapy) and the absolute claudication distance (p<0.0001) from 229.5+/-22.0 m to 365.4+/-46.9 m; meanwhile both variables remained unchanged in the placebo group (p<0.05). The reduction of lower limb symptoms showed a greater benefit in the policosanol group. There was no significant change in either group in the ankle/arm pressure ratio. The treatment was well tolerated. There were 10 discontinuations (seven placebo, three policosanol) from the study. Six withdrawals occurred because of adverse events (AE); all were in placebo patients. There were five serious vascular AEs in the placebo group but none in the policosanol group (p<0.05). Overall, 12/31 (38.7%) placebo patients and 3/31 (9.7%) policosanol patients experienced AEs after randomization, which showed a lesser incidence of AEs in the policosanol group (p<0.01). The present study demonstrates a beneficial effect of policosanol in patients with intermittent claudication.

Adult↗