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Ginkgo biloba extract for the treatment of intermittent claudication: a meta-analysis of randomized trials.

PURPOSE: The optimal treatment of intermittent claudication has not yet been identified. Ginkgo biloba extract has been reported to have beneficial effects. We performed a meta-analysis of the efficacy of Ginkgo biloba extract for intermittent claudication based on the results of randomized, placebo-controlled, double-blind trials. METHODS: Literature searches of MEDLINE, EMBASE, BIOSIS, AMED, CISCOM, and the Cochrane Library were performed to identify studies on the topic. Manufacturers of commercial Ginkgo biloba products and authors of original publications and reviews were contacted to provide additional information. No language restrictions were imposed. RESULTS: Eight randomized, placebo-controlled, double-blind trials were included. Meta-analysis found a significant difference in the increase in pain-free walking distance in favor of Ginkgo biloba (weighted mean difference: 34 meters, 95% confidence interval [CI]: 26 to 43 meters). In studies using similar methodological features (ergometer speed: 3 km/h, inclination: 12%) this difference was 33 meters in favor of Ginkgo biloba (95% CI: 22 to 43 meters). Adverse effects were rare, mild, and transient. CONCLUSIONS: These results suggest that Ginkgo biloba extract is superior to placebo in the symptomatic treatment of intermittent claudication. However, the size of the overall treatment effect is modest and of uncertain clinical relevance.

Double-Blind Method↗

Pharmacologic treatment for intermittent claudication.

In contradistinction to chronic critical limb ischemia, the peripheral arterial disease patient with intermittent claudication is at relatively low risk for limb loss. As a result, initial claudication management should employ non-interventional therapies rather than immediate catheter-based or surgical revascularization. Although exercise therapy is the most efficacious conservative treatment for claudication, supervised exercise programs are not widely available at present. Consequently, a pharmacologic agent can be utilized to lessen the symptoms and improve the function of the claudicant. This manuscript provides a comprehensive review of the various pharmacotherapies that have been investigated for improving walking distance in the setting of intermittent claudication. Cilostazol, a phosphodiesterase III inhibitor, appears to provide the greatest benefit, significantly improving not only walking distance but quality of life as well. Early trials indicate that propionyl-L-carnitine, oral prostaglandins, L-arginine, and therapeutic angiogenesis may eventually yield significant benefit in lessening the symptoms of intermittent claudication.

Clinical Trials as Topic↗

Comparison of graded versus constant treadmill test protocols for quantifying intermittent claudication.

The standard method for quantifying the symptoms of intermittent claudication is by using treadmill walking distance. It has recently been suggested that a graded exercise test is much more reproducible than a constant load exercise test. Graded protocols have also been claimed to abolish the placebo effect that has been reported with the constant load test. The reproducibility of absolute claudication distance (ACD) and initial claudication distance (ICD) using a constant load was compared to the graded load treadmill protocol. Fourteen patients (mean age 66 years) with varying severity of stable intermittent claudication were tested using a constant load (3.2 km/h, 10% gradient) and a graded load (3.2 km/h, 0% gradient increasing by 3.5% every 3 min). Patients were tested twice using each protocol in a random sequence, with a minimum 2 day interval between visits. Intra-class correlation coefficient (R) with a constant load protocol for ICD and ACD was R = 0.68, R = 0.93, respectively. With a graded protocol R = 0.84 for ICD and R = 0.98 for ACD. Relative coefficient of repeatability for ICD and ACD during constant load tests were 1.47 and 1.90 respectively and with a graded load test were 1.69 and 1.52 respectively. It was concluded that the graded load test was more reproducible than the constant load test but only by a small margin, whilst ACD was much more reproducible than ICD using either protocol.

Aged↗

Comparison of the Health Utilities Index Mark 3 (HUI3) and the EuroQol EQ-5D in patients treated for intermittent claudication.

The Health Utilities Index Mark 3 (HUI3) and the EuroQol EQ-5D (EQ-5D) were compared to each other and to other quality-of-life (QoL) measures in patients treated for intermittent claudication. A total of 88 patients with intermittent claudication completed the HUI3, EQ-5D, RAND 36-Item Health Survey 1.0, time tradeoff, standard gamble, and rating scale before revascularization and at follow-up at 1 month, 3 months, and 1 year. The effect of treatment on the HUI3 and EQ-5D dimensions and the overall scores, calculated using published formulas based on societal preferences, were compared. After 1 month of treatment, the majority of patients showed improvement on the HUI3 dimensions ambulation and pain and on the EQ-5D dimensions mobility, usual activities, and pain/discomfort. The mean HUI3 score was significantly higher than the mean EQ-5D score (0.66 and 0.57, respectively, p < 0.01) before treatment. After treatment, however, they were not significantly different from each other (e.g., 12 months after treatment: 0.77 and 0.75, respectively (p > 0.05). After 1 month, the scores did not change significantly over time (p > 0.05). The intraclass correlation coefficient between changes over time in the HUI3 and EQ-5D scores was 0.30, with other health-related quality-of-life (HRQoL) measures the correlations for HUI3 and EQ-5D were very similar. In conclusion, both the HUI3 and EQ-5D demonstrated an effect of treatment in patients with intermittent claudication; in addition, they showed similar relationships with other (HRQoL) measures. To demonstrate the effect of revascularization in patients with intermittent claudication, however, clinicians and researchers should be aware of the differences in the mean HUI3 and EQ-5D scores.

Analysis of Variance↗

The role of pedometers in the assessment of intermittent claudication.

OBJECTIVES: to evaluate the role of pedometers in the assessment of patients with intermittent claudication by comparing them with treadmill testing, post-exercise ankle brachial pressure index (ABPI) and physical function questionnaires. PATIENTS AND METHODS: fifty patients with intermittent claudication were prospectively assessed by treadmill examination measuring maximum walking distance (MWD) and post-exercise ABPI. Three physical function questionnaires: (1) Medical Outcome Study Short Form-36 (MOS SF-36), Physical Function (PF). (2) MOS SF-36 Role limitation due to Physical Problems (RP). (3) Walking Impairment Questionnaire (WIQ) were completed. Pedometers were used for one week and the daily average number of steps taken by each patient recorded. Pedometers scores were compared with MWD, post-exercise ABPI and physical function questionnaires scores using Spearman correlation test. RESULTS: pedometers estimation of daily physical activity moderately correlated with MWD (Rho=0.35, p=0.01), post-exercise ABPI (Rho=0.35, p=0.01), MOS-SF 36 PF (Rho=0.31, p=0.02), MOS-SF RP (Rho=0.28, p=0.05) and with WIQ (Rho=0.42, p=0.003). CONCLUSIONS: they moderately correlate with treadmill testing, post-exercise ABPI, and with physical function questionnaires. Pedometers may provide a simple and cheap alternative for the assessment of physical and functional disability in intermittent claudication.

Aged↗

A new device for the measurement of disease severity in patients with intermittent claudication.

OBJECTIVES: To assess a new method of determining functional impairment in patients with intermittent claudication, the Double Physiological Walking Test (DPWT) using the PADHOC (Peripheral Arterial Disease Holter Control) device, against a standard treadmill test. DESIGN: Patients with intermittent claudication presenting to the department were considered for both the DPWT and a standard treadmill test. METHODS: initial claudicating distance, maximal walking distance and speed of walking were determined for both parts of the DPWT. Initial claudicating distance and maximal walking distance were determined from the treadmill test. Comparisons were made between the treadmill test and the DPWT. RESULTS: The treadmill test was unable to be performed in 22% of patients due to defined contraindications. There were strong correlations in both walking distances and disease severity when comparing the DPWT and the treadmill test. Patients in whom the treadmill test was contraindicated had significantly shorter walking distances on the DPWT than those who were able to complete a treadmill walking test. CONCLUSIONS: The DPWT correlates strongly with walking distances obtained from a standard treadmill test. However, the PADHOC can be used in a number of differing locations and settings as well as in patients in whom a treadmill test is contraindicated. It therefore has a role to play in the initial assessment of patients presenting with intermittent claudication.

Aged↗

Prosthetic above-knee femoropopliteal bypass for intermittent claudication.

There is no consensus about the most appropriate management of the patient with intermittent claudication due to a superficial femoral artery occlusion. To evaluate the natural history of prosthetic above-knee femoropopliteal (AKFP) bypass, 200 operations for intermittent claudication were reviewed. One hundred AKFP bypasses were done with PTFE and 100 with dacron. In the 30 day postoperative period, four PTFE and three dacron grafts occluded without consequence and only one patient died. Analysis of results by the life-table method demonstrated statistically similar primary graft patency rates at five years (PTFE 65% SE +/- 6.5, dacron 57% +/- 6.2) and ten years (PTFE 31% +/- 18/9, dacron 32% +/- 13.2) (p greater than 0.10). Redo procedures (e.g., thrombectomy, angioplasty) were necessary on 21 grafts (12 PTFE, 9 dacron) and "secondary" patency rates at five years were 76% PTFE and 62% dacron; no grafts which required a redo procedure were patent at ten year follow-up. Major amputations during ten year follow-up were necessary in 16 (8%) patients; all amputations were in diabetic patients. Survival rates were 79% at five and 42% at ten years. An anticipated, the leading cause of death was cardiac related (25 patients); 28 (14%) patients underwent aortocoronary bypass during follow-up. A prosthetic AKFP bypass graft is a safe and durable operation which provides relief from the symptoms of intermittent claudication while allowing for the preservation of the saphenous vein for use later in the coronary or infrapopliteal circulations, should the need arise. These results indicate that the risk of amputation after AKFP is no greater than the natural history of untreated claudication; however, AKFP offers a significant improvement in life-style.

Adult↗

Electrophysiological studies of intermittent claudication in lumbar stenosis.

To clarify the pathophysiology of intermittent claudication in 37 patients with lumbar spinal stenosis, neural function was evaluated by examining somatosensory evoked potentials (stress-SEPs), and nerve action potentials (stress-NAPs) before and after walking stress. It was shown preoperatively that the stress-SEPs became abnormal immediately after walking in 31 of 37 patients. In seven of nine operated patients, the assessment clearly shows that SEPs had reverted to normal after surgery. The present method is noninvasive, simple in technique, painless, and safe, a procedure therefore that is useful as the initial step in the diagnosis and treatment of patients with lumbar canal stenosis. It also may help to differentiate neurogenic from vascular intermittent claudication.

Adult↗

Variability in responsiveness to clopidogrel in patients with intermittent claudication.

OBJECTIVE: The concept of clopidogrel resistance is frequently evoked in the cardiac literature. The variability of antiplatelet response in patients with intermittent claudication has not been investigated. The aim of this study was to describe the effect of the addition of clopidogrel to aspirin using ex vivo measures of platelet activation in patients with life-style limiting intermittent claudication. DESIGN OF STUDY: Data from randomised controlled trial. MATERIALS: Data from 67 patients with intermittent claudication taking part in a randomised controlled trial and who received clopidogrel in addition to aspirin was analysed. METHODS: Platelet activation was measured using whole-blood flow cytometric measurement of ADP-stimulated fibrinogen binding at baseline and 12h after administration of a loading dose of 300 mg clopidogrel. Patients continued to receive 75 mg clopidogrel daily for 30 days and platelet activation was again measured at day 30. Compliance with treatment was assessed by counting returned tablets. RESULTS: Six patients were excluded from analysis because of incomplete compliance with treatment. Six of the sixty-one patients (9.8%) showed no reduction in platelet activation 12h after administration of the loading dose of clopidogrel. At 30 days these six patients still showed no response to clopidogrel. Amongst the remaining 55 patients, the mean reduction in fibrinogen binding after clopidogrel administration was 51.5% (95% CI: 43.8-59.2). Amongst responders there was a wide variability in reduction of fibrinogen binding in response to clopidogrel (range 8.11-97.7%). Four of these patients (6.6%) showed a reduction of more than 95% in fibrinogen binding. CONCLUSIONS: Patients with intermittent claudication show a wide variability in their response to clopidogrel. While a small proportion of these patients shows no response at all, another small group appears to respond excessively to clopidogrel. Clinical studies are required to identify whether hyper-responders are at increased risk of bleeding complications and whether hyporesponders are at a higher risk of thrombotic events.

Adult↗

Co-variation between walking ability and circulatory alterations in patients with intermittent claudication.

Unselected patients (n = 183) with subjective symptoms of intermittent claudication were examined clinically and by various circulatory tests (calf blood-flow, ankle, toe pressures). The aims of the present study were to evaluate to what extent the central or peripheral circulation is limiting in unselected patients with subjective symptoms of intermittent claudication, to determine the co-variation between the maximum walking capacity and traditional haemodynamical measures mentioned above and to evaluate to what extent a traditional bicycle ergometer exercise test and treadmill walking test give similar information regarding maximum performance. Eighty-five per cent of all patients were or had been smokers and 16% were diabetics. The mean ankle/brachial blood pressure index was 0.58 +/- 0.02 and the average post-ischemic maximum calf bloodflow was 13.3 +/- 0.6 ml/min/100 ml tissue. Leg arterial insufficiency was the limiting factor of walking capacity in 90% of all patients at 87 +/- 2 W corresponding to a walking distance of 282 +/- 13 m, while leg exhaustion was the limiting factor in 80% of the patients during test on the bicycle ergometer at maximum 84 +/- 2W. The mean maximum walking capacity for all patients was 86 +/- 3W and the mean maximum capacity on the bicycle ergometer was 87 +/- 2W. The ankle/brachial index showed only a weak correlation (r = 0.30, p < 0.002) to walking capacity. Our results demonstrate that the maximum walking capacity on a treadmill agrees with mean values of maximum exercise capacity on a bicycle ergometer.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

A reliable and readily available method of measuring limb blood flow in intermittent claudication.

To evaluate isotope limb blood flow measurement in intermittent claudication we have assessed 58 non-diabetic patients comparing our new method with treadmill testing and Doppler assessment. Limb blood flow was applicable to all 58 patients; 25 patients were unable to walk on a treadmill and of the 33 who could 12 failed to walk for one minute, making a standard one minute exercise test inappropriate. In those patients who could perform exercise tests there was a significant correlation between maximum walking distance and limb blood flow (r = 0.35, P = 0.02). Resting, post-exercise and post-hyperaemic ankle-brachial systolic pressure indices bore no relationship to the maximum walking distance. Isotope limb blood flow measurement is reproducible (r = 0.97), can be applied to those patients who cannot walk on a treadmill and provides information about both legs. It correlated significantly with all the other tests and can be recommended for the minimally invasive assessment of intermittent claudication.

Adult↗

Neurogenic intermittent claudication in association with spondylolisthesis.

In the last three decades, more attention has been put upon neurogenic intermittent claudication, also called pseudoclaudication. The syndrome usually develops in patients with congenital narrow spinal canal and secondary additional narrowing. Two cases of spondylolisthesis with neurogenic intermittent claudication are presented. The pathogenesis, symptoms and findings of neurogenic intermittent claudication are discussed.

Female↗

Effect of surgical treatment on physical activity and bone resorption in patients with neurogenic intermittent claudication.

The effect of surgical treatment on physical activity and bone resorption was examined in patients with neurogenic intermittent claudication. Nineteen patients, 50-77 years of age, with neurogenic intermittent claudication (mean, 162 m; range, 20-400 m) caused by degenerative lumbar disease were included in the study. Decompressive laminectomy alone was performed for 7 patients with lumbar spinal stenosis (LSS) and 5 patients with degenerative lumbar spondylolisthesis (DLSL), and decompressive laminectomy, with a Graf stabilization system, was performed for 7 patients with DLSL associated with flexion instability. Clinical symptoms and levels of urinary cross-linked N-telopeptides of type I collagen (NTx) were assessed before and 12 months after surgery. Subjective symptoms, including low back pain, leg pain and/or tingling, and gait disturbance, as well as restriction of activities of daily living were significantly alleviated by the surgical treatment, resulting in an increase in physical activity. Urinary NTx levels were significantly decreased by the surgical treatment, from 63.1 +/- 16.9 (mean +/- SD) nmol BCE/mmol Cr to 52.1 +/-11.2 nmol BCE/mmol Cr (P < 0.05). These findings suggest that surgical treatment appears to alleviate the clinical symptoms and increase physical activity in patients with LSS or DLSL, potentially resulting in the suppression of bone resorption. Surgical treatment may contribute to the prevention of physical inactivity-induced osteoporosis in elderly patients with neurogenic intermittent claudication caused by degenerative lumbar disease.

Aged↗

Controlled trial of suloctidil in intermittent claudication.

Forty-five patients with intermittent claudication were first treated with placebo tablets for 3 months and then randomly allocated to double-blind therapy with either suloctidil or placebo for 6 months. Walking distance improved significantly in both groups during the 3 months of placebo treatment. During the 6 months of double-blind treatment with a further significant improvement occurred only in the placebo group when all patients were analyzed. However, when patients who stopped for reasons unrelated to claudication such as angina and exhaustion during repeated walking tests were eliminated, only suloctidil-treated patients improved significantly. The evolution of leg flow and distal pressure was similar in the two treatment groups whether all legs or only legs with abnormal flow and pressure values were considered. By contrast, when the analysis was limited to legs with claudication pain, a significant improvement occurred only in the suloctidil-treated group. These findings suggest that suloctidil may improve the claudication symptoms of patients with chronic arterial obstructive disease and in particular the perfusion of legs experiencing claudication pain. However, the clinical significance of this improvement appears limited.

Clinical Trials as Topic↗

Assessment of generic health-related quality of life in patients with intermittent claudication.

OBJECTIVES: to measure quality of life in patients with intermittent claudication and evaluate the ability of patients and vascular surgeons to make a similar assessment. DESIGN, MATERIALS AND METHODS: in this prospective study patients with intermittent claudication attending two vascular clinics were asked to complete a generic health-related quality of life instrument (MOS SF-36). Patient quality of life and vascular surgeons' assessment of patient quality of life were further evaluated using a single question/adjectival scale response combination. RESULTS: patients' self-assessment of their quality of life correlated better with the SF-36 score than did the surgeons' assessment. There was little correlation between the surgeons' and patients' own assessment of quality of life. The surgeons differed significantly from each other in their assessments. Claudicants had lower SF-36 scores than population norms in pain and physical aspects of quality of life. CONCLUSIONS: claudicants have worse quality of life than the general population, with pain and physical limitations being the most important domains. Surgeons predict the quality of life of claudicating patients less accurately than patients do themselves, and may differ from their colleagues in such assessments. Objective quality of life assessment in claudicants should be undertaken before treatment is decided.

Adult↗

The effect of alpha-tocopherol and beta-carotene supplementation on symptoms and progression of intermittent claudication in a controlled trial.

We evaluated the effect of long-term supplementation with vitamin E (alpha-tocopherol) and beta-carotene on occurrence of claudication symptoms and risk for peripheral vascular surgery among men with intermittent claudication. Subjects, 50-69-year old male smokers, were participants in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, who reported intermittent claudication through a structured questionnaire (Rose) at study entry (n=1484). They were randomly assigned to receive either 50 mg/day of alpha-tocopherol, or 20 mg/day of beta-carotene, or both, or placebo, in a 2 x 2 design. During follow-up, claudication was evaluated by repeating use of the questionnaire once a year. Information on peripheral vascular surgery came from the National Hospital Discharge Register. We observed no effect of alpha-tocopherol and beta-carotene supplementation on claudication during a mean follow-up of 3.7 years. A slightly increased risk (odds ratio (OR) 1.60, 95% confidence interval (CI) 1.05-2.44) for vascular surgery was observed among beta-carotene supplemented men compared to those who did not receive beta-carotene. Alpha-tocopherol supplementation had no effect. In conclusion, long-term supplementation with alpha-tocopherol and beta-carotene showed no beneficial effect on symptoms and progression of intermittent claudication.

Aged↗

Phenol sympathectomy in the treatment of intermittent claudication: a controlled clinical trail.

Twenty-five patients with intermittent claudication were randomly allocated to treatment either by injection of phenol into the lumbar sympathetic chain or by injection of local anaesthetic subcutaneously. On the day after the injection, sympathectomy, assessed by skin temperature change, was achieved in 85 per cent of the phenol group. At 1 month subjective improvement was claimed by 45 per cent of the patients in the sympathectomized group and by 64 per cent in the control group; at 3 months the figures were 25 and 45 per cent respectively. Treadmill testing at two exercise loads showed no significant difference in claudication distance or stopping time between the two groups. Calf blood pressure response following exercise was not affected by sympathectomy. There is no subjective or objective evidence that phenol sympathectomy improves intermittent claudication.

Blood Pressure↗