Ginkgo biloba for intermittent claudication.

BACKGROUND: People with intermittent claudication (IC) suffer from pain in the muscles of the leg occurring during exercise which is relieved by a short period of rest. Symptomatic relief can be achieved by (supervised) exercise therapy and pharmacological treatments. Ginkgo biloba is a vasoactive agent and is used to treat IC. OBJECTIVES: To assess the effect of Ginkgo biloba on walking distance in people with intermittent claudication. SEARCH METHODS: For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (March 2013) and CENTRAL (2013, Issue 2). SELECTION CRITERIA: Randomised controlled trials of Ginkgo biloba extract, irrespective of dosage, versus placebo in people with IC. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trials for selection, assessed study quality and extracted data. We extracted number of patients, mean walking distances or times and standard deviations. To standardise walking distance or time, caloric expenditures were used to express the difference between the different treadmill protocols, which were calculated from the speed and incline of the treadmill. MAIN RESULTS: Fourteen trials with a total of 739 participants were included. Eleven trials involving 477 participants compared Ginkgo biloba with placebo and assessed the absolute claudication distance (ACD). Following treatment with Ginkgo biloba at the end of the study the ACD increased with an overall effect size of 3.57 kilocalories (confidence interval (CI) -0.10 to 7.23, P = 0.06), compared with placebo. This translates to an increase of just 64.5 ( CI -1.8 to 130.7) metres on a flat treadmill with an average speed of 3.2 km/h. Publication bias leading to missing data or "negative" trials is likely to have inflated the effect size. AUTHORS' CONCLUSIONS: Overall, there is no evidence that Ginkgo biloba has a clinically significant benefit for patients with peripheral arterial disease.

Effect of supervised exercise therapy for intermittent claudication in patients with diabetes mellitus.

BACKGROUND: Primary treatment for patients with intermittent claudication is exercise therapy. Diabetes mellitus (DM) is a frequently occurring comorbidity in patients with intermittent claudication, and in these patients, exercise tolerance is decreased. However, there is little literature about the increase in walking distance after supervised exercise therapy (SET) in patients with both intermittent claudication and DM. The objective of this study was to determine the effectiveness of SET for intermittent claudication in patients with DM. METHODS: Consecutive patients with intermittent claudication who started SET were included. Exclusion criteria were Rutherford stage 4 to 6 and the inability to perform the standardized treadmill test. SET was administered according to the guidelines of the Royal Dutch Society for Physiotherapy. At baseline and at 1, 3, and 6 months of follow-up, a standardized treadmill exercise test was performed. The primary outcome measurement was the absolute claudication distance (ACD). RESULTS: We included 775 patients, of whom 230 had DM (29.7%). At 6 months of follow-up, data of 440 patients were available. Both ACD at baseline and at 6 months of follow-up were significantly lower in patients with DM (P < 0.001). However, increase in ACD after 6 months of SET did not differ significantly (P = 0.48) between the DM group and the non-DM group (270 m and 400 m, respectively). CONCLUSION: In conclusion, SET for patients with intermittent claudication is equally effective in improving walking distance for both patients with and without DM, although ACD remains lower in patients with DM.

Additional supervised exercise therapy after a percutaneous vascular intervention for peripheral arterial disease: a randomized clinical trial.

PURPOSE: To determine whether a percutaneous vascular intervention (PVI) combined with supplemental supervised exercise therapy (SET) is more effective than a PVI alone in improving walking ability in patients with symptomatic peripheral arterial disease (PAD). MATERIALS AND METHODS: In this prospective randomized trial, patients with PAD treated with a PVI were eligible. Exclusion criteria were major amputation or tissue loss, comorbidity preventing physical activity, insufficient knowledge of the Dutch language, no insurance for SET, and prior participation in a SET program. All patients received a PVI and subsequently were randomly assigned to either the PVI alone group (n = 35) or the PVI + SET group (n = 35). The primary outcome parameter was the absolute claudication distance (ACD). This trial was registered at Clinical trials.gov, NCT00497445. RESULTS: The study included 70 patients, most of whom were treated for an aortoiliac lesion. The mean difference in ACD at 6 months of follow-up was 271.3 m (95% confidence interval [CI] 64.0-478.6, P = .011) in favor of additional SET. In the PVI alone group, 1 (3.7%) patient finished the complete treadmill test compared with 11 (32.4%) patients in the PVI + SET group (P = .005). Physical health-related quality-of-life score was 44.1 ± 7.8 in the PVI alone group compared with 41.9 ± 9.5 in the PVI + SET group, which was a nonsignificant difference (P = .34). CONCLUSIONS: SET following a PVI is more effective in increasing walking distance compared with a PVI alone. These data indicate that SET is a useful adjunct to a PVI for the treatment of PAD.

Multicenter randomized clinical trial of supervised exercise therapy with or without feedback versus walking advice for intermittent claudication.

OBJECTIVE: The initial treatment for intermittent claudication is supervised exercise therapy (SET). Owing to limited capacity and patient transports costs of clinic-based SET, a concept of SET provided by local physiotherapists was developed. We hypothesized that provision of daily feedback with an accelerometer in addition to SET would further increase walking distance. METHODS: This multicenter randomized trial was set in vascular surgery outpatient clinics and included 304 patients with intermittent claudication. Patients were randomized to exercise therapy in the form of "go home and walk" advice (WA), SET, or SET with feedback. Local physiotherapists provided SET. The primary outcome measure was the change in absolute claudication distance. Secondary outcomes were the change in functional claudication distance and results on the Walking Impairment Questionnaire (WIQ) and Short-Form 36 (SF-36) Health Survey after 12 months. RESULTS: In 11 centers, 102, 109, and 93 patients were included, respectively, in the WA, SET, and SET with feedback groups, and data for 83, 93, and 76, respectively, could be analyzed. The median (interquartile range) change in walking distance between 12 months and baseline in meters was 110 (0-300) in the WA group, 310 (145-995) in the SET group, and 360 (173-697) in the SET with feedback group (P < .001 WA vs SET). WIQ scores and relevant domains of the SF-36 improved statistically significantly in the SET groups. CONCLUSIONS: SET is more effective than WA in improving walking distance, WIQ scores, and quality of life for patients with intermittent claudication. Additional feedback with an accelerometer did not result in further improvement. SET programs should be made available for all patients with intermittent claudication.

Optimizing supervised exercise therapy for patients with intermittent claudication.

BACKGROUND: The first-line intervention for intermittent claudication is usually supervised exercise therapy (SET). The literature describes a range of exercise programs varying in setting, duration, and content. The purpose of the present study was to examine the exercise protocols offered and to identify the impact of the intensity of the SET programs (in terms of frequency, duration, and type of exercise) on improvements in walking distance (response) in the first 3 months. The present study is part of the Exercise Therapy in Peripheral Arterial Disease (EXITPAD) study, a multicenter randomized clinical trial comparing the effects of SET provided by regional physiotherapists, with or without daily feedback, on the level of activities with the effects of walking advice. METHODS: The analysis included patients randomized to receive SET with or without feedback. The physical therapists administering the SET were asked to fill out therapy evaluation sheets stating frequency, duration, and type of exercises. The relationship between training volume and the impact on walking distance was explored by dividing training volume data into tertiles and relating them to the median change in maximum walking distance at 3 and 12 months. RESULTS: Data of 169 patients were included in the analysis. A SET program consisting of at least two training sessions per week each lasting over 30 minutes, during the first 3 months of a 1-year program tailored to individual patients' needs led to better results in terms of walking distance after 3 and 12 months than the other variants. The results of our analysis dividing training volume into tertiles suggest that there is a relationship between training volume and improvement in walking distance and that at least 590 minutes of training should be offered in the first 3 months. No differences were found between program involving only walking and a combination of exercises, nor between individual and group training. CONCLUSION: A SET programs consisting of at least two training sessions a week, each lasting over 30 minutes, should be offered during the first 3 months of the SET program to optimize improvement in terms of maximum walking distance.

Supervised exercise therapy for intermittent claudication in daily practice.

OBJECTIVE: This study describes the results and functioning of community-based supervised exercise therapy (SET) at one year of follow-up. METHODS: We conducted a prospective cohort study of community-based SET in regional physiotherapeutic practices. Consecutive patients with intermittent claudication referred for community-based SET were included. Exclusion criteria for SET were pain at rest or tissue loss. All patients received a diagnostic workup consisting of an ankle-brachial index at rest and after exercise. Interventions were exercise therapy according to the guidelines of the Royal Dutch Society for Physiotherapy. The primary outcome measurement was the increase in absolute claudication distance (ACD), assessed using a standardized treadmill protocol by a physiotherapist at baseline and at four, 12, 26, and 52 weeks of SET. RESULTS: From January 2005 through September 2006, 349 patients were referred by vascular surgeons for community-based SET. A total of 272 patients with intermittent claudication began the program. Of the 349 initially referred patients, 52 could not perform a standard treadmill test but did start community-based SET at a lower level, and 25 patients never started the program. At one year, 129 of the original 272 patients who began community-based SET (47.4%) were available for analysis of walking distance. In the interim, 143 patients discontinued the program for the following reasons: satisfaction with the acquired walking distance (n = 19); unsatisfying results (n = 26); not motivated (n = 22); (non)vascular intercurrent disease (n = 48); and other reasons (n = 28). ACD increased significantly from a median of 400 m at baseline to 1100 m after 12 months of follow-up (P < .001), corresponding to a median increase of 107.8%. CONCLUSION: Community-based SET seems as effective as SET in a hospital-based approach in improving walking distance, however, it has a high dropout rate.

The walking impairment questionnaire: an effective tool to assess the effect of treatment in patients with intermittent claudication.

OBJECTIVE: Assessment of walking distance by treadmill testing is the most commonly used method to evaluate the effect of treatment in patients with peripheral arterial disease. However, treadmill testing is time consuming, relatively expensive, and does not adequately reflect real life functional ability. We hypothesized that the Walking Impairment Questionnaire (WIQ) could be an alternative tool to assess objective improvement in functional walking ability of patients with intermittent claudication. METHODS: This was a validation study. It was conducted through the outpatient clinic for vascular surgery. Patients with intermittent claudication were referred for supervised exercise therapy. Treadmill testing (absolute claudication distance [ACD]), WIQ, and quality of life questionnaires (RAND-36 and EuroQol) were administered at study onset and after 3 months of supervised exercise therapy. Responsiveness was determined by mean changes in and correlation coefficients of WIQ, ACD, and quality of life questionnaires. Patients were categorized into quartiles based on the increase in ACD, which were subsequently related to change in WIQ and quality of life. RESULTS: The mean pre- and post-treatment total WIQ scores of 91 patients were 0.45 (0.22) and 0.58 (0.22), respectively. The correlation coefficient between the change in total WIQ score and ACD was 0.331 (P = .004). A 0.1 change in total WIQ score corresponded to a change of 345 meters in ACD. Analysis of the four quartiles compared to an increase in ACD showed that a greater increase in ACD corresponded with a greater increase in WIQ score, from 0.06 to 0.25 (P = .011). CONCLUSION: These data indicate that the WIQ is a valid tool to detect improvement or deterioration in the daily walking ability of patients with intermittent claudication. Hence, the WIQ can be used as an alternative to treadmill testing for objective assessment of functional walking ability, both in daily practice and in clinical trials.

Reliability of treadmill testing in peripheral arterial disease: a meta-regression analysis.

OBJECTIVE: A meta-regression analysis was conducted to identify the most reliable treadmill protocol for the assessment of patients with peripheral arterial disease (PAD). BACKGROUND: Treadmill testing is the main assessment method to evaluate walking ability in patients with PAD in clinical studies. Reported treadmill protocols are continuous (C) and graded (G) protocols and outcome measurements are initial claudication distance (ICD) and absolute claudication distance (ACD). Variety in protocols might hamper the ability to compare results of different studies. Ideally, future studies should use a protocol with highest reliability. METHODS: We searched PubMed and EMBASE (until February 2008) and we hand searched the reference lists. Trials assessing reliability of treadmill testing were identified. Inclusion criteria were the use of a C- or G-protocol, repetition of this protocol, and a retrievable intraclass correlation coefficient (ICC). We identified eight studies in which 658 patients were included. RESULTS: For ICD, the estimated reliabilities of the C- and G-protocol (as assessed by the ICC) were 0.85 (95% confidence interval [CI]: 0.82-0.88) and 0.83 (95% CI: 0.80-0.85), respectively, without dependency of the reliability on velocity or grade. For ACD, the reliability was significantly better for the G-protocol (0.95, 95% CI: 0.94-0.96) than for the C-protocol. Moreover, the reliability of the C-protocol was dependent on grade of the treadmill (0%, 10%, and 12%) with a mean ICC of 0.76 (95% CI: 0.54-0.88), 0.89 (95% CI: 0.86-0.91), and 0.91 (95% CI 0.88-0.92), respectively. CONCLUSION: Treadmill assessment has the highest reliability when using a G-protocol together with the ACD as the primary outcome measure.

Functional claudication distance: a reliable and valid measurement to assess functional limitation in patients with intermittent claudication.

BACKGROUND: Disease severity and functional impairment in patients with intermittent claudication is usually quantified by the measurement of pain-free walking distance (intermittent claudication distance, ICD) and maximal walking distance (absolute claudication distance, ACD). However, the distance at which a patient would prefer to stop because of claudication pain seems a definition that is more correspondent with the actual daily life walking distance. We conducted a study in which the distance a patient prefers to stop was defined as the functional claudication distance (FCD), and estimated the reliability and validity of this measurement. METHODS: In this clinical validity study we included patients with intermittent claudication, following a supervised exercise therapy program. The first study part consisted of two standardised treadmill tests. During each test ICD, FCD and ACD were determined. Primary endpoint was the reliability as represented by the calculated intra-class correlation coefficients. In the second study part patients performed a standardised treadmill test and filled out the Rand-36 questionnaire. Spearman's rho was calculated to assess validity. RESULTS: The intra-class correlation coefficients of ICD, FCD and ACD were 0.940, 0.959, and 0.975 respectively. FCD correlated significantly with five out of nine domains, namely physical function (rho = 0.571), physical role (rho = 0.532), vitality (rho = 0.416), pain (rho = 0.416) and health change (rho = 0.414). CONCLUSION: FCD is a reliable and valid measurement for determining functional capacity in trained patients with intermittent claudication. Furthermore it seems that FCD better reflects the actual functional impairment. In future studies, FCD could be used alongside ICD and ACD.

Ginkgo biloba for intermittent claudication.

BACKGROUND: People with intermittent claudication suffer from pain in the muscles of the leg occurring during exercise which is relieved by a short period of rest. Symptomatic relief can be achieved by (supervised) exercise therapy and pharmacological treatments. Ginkgo biloba is a vasoactive agent and is used to treat intermittent claudication. OBJECTIVES: To assess the effect of Ginkgo biloba on walking distance in people with intermittent claudication. SEARCH STRATEGY: The Cochrane Peripheral Vascular Diseases (PVD) Group searched their Trials Register (last searched 3 February 2009) and the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (last searched 2009, Issue 1). We searched MEDLINE/PUBMED (January 1966 to May 2008) and EMBASE (January 1985 to May 2008) and contacted manufacturers. SELECTION CRITERIA: Randomised controlled trials of Ginkgo biloba extract, irrespective of dosage, versus placebo in people with intermittent claudication. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trials for selection, assessed study quality and extracted data. We extracted number of patients, mean walking distances or times and standard deviations. To standardise walking distance or time, caloric expenditures were used to express the difference between the different treadmill protocols, which were calculated from the speed and incline of the treadmill. MAIN RESULTS: Fourteen trials with a total of 739 participants were included. Eleven trials involving 477 participants compared Ginkgo biloba with placebo and assessed the absolute claudication distance. Following treatment with Ginkgo biloba at the end of the study the absolute claudication distance increased with an overall effect size of 3.57 kilocalories (confidence interval -0.10 to 7.23, P = 0.06), compared with placebo. This translates to an increase of just 64.5 (confidence interval -1.8 to 130.7) metres on a flat treadmill with an average speed of 3.2 km/h. Publication bias leading to missing data or "negative" trials is likely to have inflated the effect size. AUTHORS' CONCLUSIONS: Overall, there is no evidence that Ginkgo biloba has a clinically significant benefit for patients with peripheral arterial disease.

Pocket Doppler and vascular laboratory equipment yield comparable results for ankle brachial index measurement.

BACKGROUND: The ankle brachial index (ABI) is a well-established tool for screening and diagnosis of peripheral arterial disease (PAD). In this study we assessed the validity of ABI determination using a pocket Doppler device compared with automatic vascular laboratory measurement in patients suspected of PAD. METHODS: Consecutive patients with symptoms of PAD referred for ABI measurement between December 2006 and August 2007 were included. Resting ABI was determined with a pocket Doppler, followed by ABI measurement with automatic vascular laboratory equipment, performed by an experienced vascular technician. The leg with the lowest ABI was used for analysis. RESULTS: From 99 patients the mean resting ABI was 0.80 measured with the pocket Doppler and 0.85 measured with vascular laboratory equipment. A Bland-Altman plot demonstrated great correspondence between the two methods. The mean difference between the two methods was 0.05 (P < .001). Multivariate linear regression analysis showed no dependency of the difference on either the average measured ABI or affected or unaffected leg. CONCLUSION: Since the small, albeit statistically significant, difference between the two methods is not clinically relevant, our study demonstrates that ABI measurements with pocket Doppler and vascular laboratory equipment yield comparable results and can replace each other. Results support the use of the pocket Doppler for screening of PAD, allowing initiation of cardiovascular risk factor management in primary care, provided that the equipment operator is experienced.

Extending the range of treadmill testing for patients with intermittent claudication.

PURPOSE: There is a need to evaluate patients with peripheral arterial disease (PAD) with a limited or extended walking distance. We aimed to enable an estimation of walking distance as measured on a frequently used "standard" graded (3.2 km·h(-1), 2% increase per 2 min) protocol for walking distances measured on protocols with a lower or higher workload. METHODS: Patients with PAD and an absolute claudication distance (ACD) of <500 or between 1000 and 1600 m as measured with the "standard" protocol were included. Four graded study treadmill protocols, two with lower and two with higher workload than the "standard" protocol, were developed. Two study protocols (low or high) and the "standard" protocol were repeated in random order. Quality was determined with the intraclass correlation coefficient and the coefficient of variation. Orthogonal regression analysis was used to predict walking distances on the standard protocol on the basis of the study protocols. RESULTS: Forty-three patients with an ACD <500 m and 23 patients with an ACD between 1000 and 1600 m were included. Because feasibility from the protocols with 2.0 km·h(-1) and 2% increase every 2 min and 4.4 km·h(-1) and 2% increase every minute was highest, they were calibrated against the "standard" protocol, and reliability was comparable with the "standard" protocol. The coefficient of variation between the prediction of walking distance on the "standard" protocol on the basis of the new protocols and the measured distances were in the same range (22%-25%) as the variation measured performing the same treadmill test twice. CONCLUSIONS: An accurate estimate of walking distance as measured on a "standard" treadmill protocol can be derived from a protocol with a lower or higher workload.

Ankle brachial index measurement in primary care: are we doing it right?

BACKGROUND: The reference standard for diagnosing peripheral arterial disease in primary care is the ankle brachial index (ABI). Various methods to measure ankle and brachial blood pressures and to calculate the index are described. AIM: To compare the ABI measurements performed in primary care with those performed in the vascular laboratory. Furthermore, an inventory was made of methods used to determine the ABI in primary care. DESIGN OF STUDY: Cross-sectional study. SETTING: Primary care practice and outpatient clinic. METHOD: Consecutive patients suspected of peripheral arterial disease based on ABI assessment in primary care practices were included. The ABI measurements were repeated in the vascular laboratory. Referring GPs were interviewed about method of measurement and calculation of the index. From each patient the leg with the lower ABI was used for analysis. RESULTS: Ninety-nine patients of 45 primary care practices with a mean ABI of 0.80 (standard deviation [SD] = 0.27) were included. The mean ABI as measured in the vascular laboratory was 0.82 (SD = 0.26). A Bland-Altman plot demonstrated great variability between ABI measurements in primary care practice and the vascular laboratory. Both method of blood pressure measurements and method of calculating the ABI differed greatly between primary care practices. CONCLUSION: This study demonstrates that the ABI is often not correctly determined in primary care practice. This phenomenon seems to be due to inaccurate methods for both blood pressure measurements and calculation of the index. A guideline for determining the ABI with a hand-held Doppler, and a training programme seem necessary.

Supervised exercise therapy for intermittent claudication in a community-based setting is as effective as clinic-based.

OBJECTIVE: This cohort study was conducted to determine the effect on walking distances of supervised exercise therapy provided in a community-based setting. METHODS: The study included all consecutive patients presenting at the vascular outpatient clinic with intermittent claudication, diagnosed by a resting ankle brachial index<0.9, who had no previous peripheral vascular intervention for peripheral arterial disease, no major amputation, and sufficient command of the Dutch language. The exclusion criterion was the inability to walk the baseline treadmill test for a minimum of 10 m. The intervention was a supervised exercise therapy in a community-based setting. A progressive treadmill test at baseline and at 1, 3, and 6 months of follow-up measured initial claudication distance and absolute claudication distance. Changes were calculated using the mean percentages of change. RESULTS: From January through October 2005, 93 consecutive patients with claudication were eligible. Overall, 37 patients discontinued the supervised exercise therapy program. Eleven stopped because of intercurrent diseases, whereas for 10, supervised exercise therapy did not lead to adequate improvement and they underwent a vascular intervention. Three patients quit the program, stating that they were satisfied with the regained walking distance and did not require further supervised exercise therapy. Ten patients were not motivated sufficiently to continue the program, and in three patients, a lack of adequate insurance coverage was the reason for dropping out. Data for 56 patients were used and showed a mean percentage increase in initial claudication distance of 187% after 3 months and 240% after 6 months. The mean percentage of the absolute claudication distance increased 142% after 3 months and 191% after 6 months. CONCLUSION: Supervised exercise therapy in a community-based setting is a promising approach to providing conservative treatment for patients with intermittent claudication.