Onset Of Claudication Research Articles

Peripheral arterial disease affects kinematics during walking

Claudication is the most common manifestation of peripheral arterial disease (PAD) producing significant ambulatory compromise. The purpose of this study was to use advanced biomechanical analysis to characterize the kinematic ambulatory pattern of claudicating patients. We hypothesized that compared with control subjects, claudicating patients have altered kinematic gait patterns that can be fully characterized utilizing advanced biomechanical analysis. The study examined fourteen PAD patients (age: 58 +/- 3.4 years; weight: 80.99 +/- 15.64 kg) with clinically diagnosed femoro-popliteal occlusive disease (Ankle Brachial Index (ABI): 0.56 +/- 0.03, range 0.45 to 0.65) and five healthy controls (age: 53 +/- 3.4 years; weight: 87.38 +/- 12.75 kg; ABI >or= 1). Kinematic parameters (hip, knee, and ankle joint angles in the sagittal plane) were evaluated during gait in patients before and after the onset of claudication pain and compared with healthy controls. Joint angles were calculated during stance time. Dependent variables were assessed (maximum and minimum flexion and extension angles and ranges of motion) and mean ensemble curves were generated. Time to occurrence of the discrete variables was also identified. Significantly greater ankle plantar flexion in early stance and ankle range of motion during stance was observed in PAD patients (P < .05). Time to maximum ankle plantar flexion was shorter and time to maximum ankle dorsiflexion was longer in PAD patients (P < .05). These differences were noted when comparing PAD patients prior to and after the onset of claudication with healthy controls. The analysis of the kinematic parameters of the knee and the hip joints revealed no significant differences between PAD patients and controls. PAD patients with claudication demonstrate significant gait alterations in the ankle joint that are present prior to the onset of claudication pain. In contrast, the joint motion of the hip and knee did not differ in PAD patients when compared with controls. Further research is needed to verify our findings and assess the impact of more proximal disease in PAD patients as well as the effect of revascularization on joint kinematics.

Gene therapy as a novel therapeutic option in the treatment of peripheral vascular disease: systematic review and meta-analysis

Stimulation of therapeutic angiogenesis using gene therapy is a novel intervention for peripheral vascular disease (PVD). Despite encouraging outcomes from animal studies and phase 1 trials, results from larger trials in this area have been conflicting. We undertook a systematic review and meta-analysis of randomised controlled trials in this field, to clarify the current situation. Medline, Embase, trial registries, the American Heart Association (AHA) abstract database and article reference lists were searched to identify randomised controlled trials of gene therapy for treatment of PVD. The outcomes were change in peak walking time and claudication onset time at 90 and 180 days post-treatment, and change in ankle-brachial pressure index (ABPI) at 90 days. Weighted mean differences (WMD) were calculated for these outcomes. Five eligible randomised clinical trials were identified, containing 508 patients. There were no significant differences between control and intervention groups for any outcomes, irrespective of whether low-dose or high-dose gene therapy was tried. The available data suggests that gene therapy confers no benefit on patients with PVD. Closer examination of the individual trials shows that several have an excessive placebo response, which may go some way to explaining our result. Further research in this area in needed.

Confiabilidade de testes de caminhada em pacientes claudicantes: estudo piloto

CONTEXTO: Uma vez que a obstrução arterial periférica pode se apresentar de maneira difusa, com clínica diversa e com resultados de intervenção variados, é fundamental que a avaliação dos pacientes com doença arterial obstrutiva periférica seja feita com instrumentos que possam apresentar dados objetivos e reprodutíveis. OBJETIVO: Investigar e contrastar a confiabilidade do teste de caminhada de 6 minutos (T6M) com teste de deslocamento bidirecional progressivo (TDBP) em indivíduos claudicantes portadores de doença arterial obstrutiva periférica. MÉTODOS: Quatorze pacientes em estágio II de Fontaine participaram deste estudo piloto. Onze pacientes realizaram ambos os testes e três realizaram apenas T6M. Após familiarização, os pacientes foram avaliados em duas ocasiões distintas com intervalo máximo de 1 semana entre si. O coeficiente de correlação de intraclasse (ICC2,1) foi utilizado para avaliação da reprodutibilidade teste-reteste. RESULTADOS: A média da distância máxima de caminhada no teste e no reteste no T6M foi de 397,04±120,74 e 408,6±153,64 metros (p = 0,58), respectivamente, com ICC = 0,87 (p = 0,00005); já no TDBP, a média foi de 345±145,75 metros e, no reteste, de 345,91±127,97 (p = 0,92), com ICC = 0,99 (p = 0,00005). O tempo médio para surgimento da dor inicial, em segundos, com o T6M, foi de 172,25±88,23 (teste) e 148,58±70,36 (reteste) (p = 0,13), com ICC = 0,81 (p = 0,0004). No TDBP, o tempo médio foi de 282±141,90 (teste) e 267,14±150,58 (reteste) (p = 0,55), com ICC = 0,91 (p = 0,0008). CONCLUSÃO: Ambos os testes de caminhada são confiáveis e úteis para avaliação clínico-funcional desses pacientes. O TDBP, entretanto, gerou índices de confiabilidade mais elevados, podendo ser melhor opção para avaliação da performance desses indivíduos.

Safety and effectiveness of the power-pulse spray in treating patients with recent onset of claudication and limb ischemia

Safety and effectiveness of the power-pulse spray in treating patients with recent onset of claudication and limb ischemia

Peripheral arterial disease in the elderly.

Smoking should be stopped and hypertension, diabetes mellitus, dyslipidemia, and hypothyroidism treated in elderly patients with peripheral arterial disease (PAD) of the lower extremities. Statins reduce the incidence of intermittent claudication and improve exercise duration until the onset of intermittent claudication in patients with PAD and hypercholesterolemia. Antiplatelet drugs such as aspirin or clopidogrel, especially clopidogrel, angiotensin-converting enzyme inhibitors, and statins should be given to all elderly patients with PAD without contraindications to these drugs. Beta blockers should be given if coronary artery disease is present. Exercise rehabilitation programs and cilostazol increase exercise time until intermittent claudication develops. Chelation therapy should be avoided. Indications for lower extremity percutaneous transluminal angioplasty or bypass surgery are (1) incapacitating claudication in patients interfering with work or lifestyle; (2) limb salvage in patients with limb-threatening ischemia as manifested by rest pain, nonhealing ulcers, and/or infection or gangrene; and (3) vasculogenic impotence.

Correlação entre o índice tornozelo-braço antes e após teste de deslocamento bidirecional progressivo

CONTEXTO: A alteração de fluxo sangüíneo observada nos pacientes com doença arterial obstrutiva periférica (DAOP) contribui para a redução da capacidade deambulatórida. Entretanto, ainda existe uma grande variabilidade nas correlações entre medidas inferenciais de comprometimento de fluxo e testes de deslocamento. OBJETIVO: Estabelecer o nível de correlação entre as medidas do índice tornozelo-braço (ITB), pré e pós-esforço, com um novo teste de deambulação chamado teste de deslocamento bidirecional progressivo (TDBP). MÉTODOS: Vinte e um pacientes claudicantes, com diagnóstico de DAOP, tiveram registrados o ITB antes e após a realização de um teste de caminhada no solo, com controle externo e progressivo de velocidade (TDBP). RESULTADOS: Foram registrados a distância (261,07±160,63 metros), o tempo (292,30±122,61 segundos) e a velocidade (1,23±0,34 m/s) obtidos no início do surgimento de sintoma claudicante, bem como durante o surgimento de sintoma limitante (369,52±157,97 metros, 377,71±104,60 segundos, 1,46±0,29 m/s, respectivamente). A média do ITB de repouso foi de 0,66±0,14, e de pós-esforço foi de 0,42±0,19. Não se observou nenhuma correlação importante entre as variáveis do teste (distância, tempo e velocidade) com o ITB de repouso e nem após esforço. CONCLUSÃO: O tempo, velocidade e distância de surgimento de sintoma claudicante e de sintoma claudicante limitante durante o teste de caminhada progressiva são independentes da medida inferencial de fluxo sangüíneo através do ITB de repouso e pós-exercício.

Management of Peripheral Arterial Disease of the Lower Extremities

Smoking should be stopped and hypertension, diabetes mellitus, dyslipidemia, and hypothyroidism treated in patients with peripheral arterial disease (PAD) of the lower extremities. Statins decrease the incidence of intermittent claudication and improve exercise duration until the onset of intermittent claudication in persons with PAD and hypercholesterolemia. Antiplatelet drugs such as aspirin or clopidogrel, especially clopidogrel, angiotensin-converting enzyme inhibitors, and statins should be given to all persons with PAD. Beta blockers should be given if coronary artery disease is present. Exercise rehabilitation programs and cilostazol increase exercise time until intermittent claudication develops. Chelation therapy should be avoided. Indications for lower extremity percutaneous transluminal angioplasty or bypass surgery are (1) incapacitating claudication in persons interfering with work or lifestyle, (2) limb salvage in persons with limb-threatening ischemia as manifested by rest pain, nonhealing ulcers, and/or infection or gangrene, and (3) vasculogenic impotence.

Peripheral arterial disease affects ground reaction forces during walking

Claudication is the most common manifestation of peripheral arterial disease (PAD), producing significant ambulatory compromise. The gait of claudicating patients has been evaluated using primarily temporal and spatial parameters. With the present study, we used advanced biomechanical measures to further delineate the ambulatory impairment of claudicating patients. We hypothesized that the claudicating legs of PAD patients have an altered kinetic gait pattern compared with normal legs from control subjects. Ambulation kinetics (ground reaction forces) were evaluated in claudicating patients and compared with age-matched healthy controls. Forces were analyzed in the vertical, anterior-posterior, and medial-lateral directions. Time from heel touch-down to toe-off (stance time) and time spent in double-limb support were also evaluated. The study recruited 14 PAD patients (age, 58 +/- 3.4 years; weight, 80.99 +/- 15.64 kg) with femoropopliteal occlusive disease (ankle-brachial index [ABI], 0.56 +/- 0.03) and five controls (age, 53 +/- 3.4 years; weight, 87.38 +/- 12.75 kg; ABI, >or=1.00). Vertical force curve evaluation demonstrated significant flattening in claudicating patients resulting in a lower and less fluctuant center of mass when ambulating. In the anterior-posterior direction, claudicating patients demonstrated significantly decreased propulsion forces. In the medial-lateral direction, they had significantly increased forces consistent with wider steps and an inability to swing their legs straight through. Claudicating patients demonstrated a greater stance time and time in double limb support compared with healthy controls. Most importantly, gait abnormalities were present before the onset of claudication, with gait worsening after the onset of claudication. Claudicating patients demonstrate significant gait impairments that are present even before they experience any limb discomfort. These alterations may make them feel more stable and secure while attempting to minimize use of the affected limb. Advanced biomechanical analysis, using ambulation kinetics, permits objective and quantitative evaluation of the gaits of claudicating patients. Such evaluation may point to new rehabilitation strategies and provide objective measurement of functional outcomes after medical and surgical therapy.

Gait abnormalities are present prior to the onset of claudication in both young and old claudicants

Gait abnormalities are present prior to the onset of claudication in both young and old claudicants

Bilateral Dissection of External Iliac Artery

External iliac artery (EIA) dissection and especially bilateral involvement is very rare. We report the case of a 49-year-old male intense bicyclist who had presented a dissection of the left EIA responsible for claudication. He underwent an iliofemoral vein graft bypass. The histopathologic examination showed a dissection of the EIA with an otherwise normal arterial wall. Two years after he resumed his sporting activity, a dissection of the right EIA occurred with the onset of claudication. The patient underwent a right iliofemoral vein graft bypass. Histopathologic examination showed the same lesions as on the left side. Bilateral involvement of EIA dissection is possible especially when the mechanism leading to dissection is persistent. An attentive follow-up is thus to consider.

Optimal assessment of baseline treadmill walking performance in claudication clinical trials

Treadmill testing is frequently used to assess the functional capacity of patients with claudication, but the optimal application of treadmill testing in the setting of multicenter clinical trials remains uncertain. The current study used data from a recent clinical trial of the drug NM-702, which employed three baseline assessments of peak walking time (PWT) using a graded treadmill. These data were used to describe the different methods of defining the baseline peak treadmill performance with respect to reproducibility, stability over time and detection of treatment effect. A series of baseline definitions (first test only, last test only, highest PWT of the three tests, arithmetic mean of the three tests, mean of the first two tests, median of the three tests and a reproducibility-based criterion) were used to calculate the population (n = 386) variability in baseline testing, the placebo response over the 24 weeks of treatment, and the effect size of NM-702. Placebo responses and NM-702 effect sizes were not substantively affected by the method used to calculate baseline PWT. Changes in PWT on placebo were less than 25% for all methods of baseline quantitation. No method yielded an NM-702 effect size quantitatively greater than that obtained using only the first baseline test in the analysis for either PWT or claudication onset time. The graded treadmill test quantifies PWT with high reproducibility and stability over time. These characteristics may obviate the need for multiple treadmill tests, potentially saving study costs and improving patient acceptance of trial participation.

Results from a phase II multicenter, double-blind placebo-controlled study of Del-1 (VLTS-589) for intermittent claudication in subjects with peripheral arterial disease

This study compared VLTS-589 (plasmid encoding the angiomatrix protein Del-1 in conjunction with poloxamer 188) with poloxamer 188 control, for the treatment of intermittent claudication in patients with moderate to severe peripheral arterial disease. Subjects with bilateral intermittent claudication and peak walking time (PWT) between 1 and 10 minutes on 2 qualifying (reproducible; within 25% of each other) treadmill tests were enrolled. Patients received VLTS-589 or poloxamer 188 control, administered as 21 intramuscular injections to each lower extremity (42 mL in each extremity). In addition to safety and tolerability, efficacy evaluations compared to baseline included the following: change in PWT at 90 days (primary end point), change in claudication onset time, change in ankle brachial index (ABI), and change in quality of life measures. A total of 105 patients were randomized and treated. During the 30, 90, and 180 days follow-up, mean PWT, claudication onset time, and ABI were significantly increased compared to baseline values in both treatment groups with no significant difference between groups in the primary or secondary end points. In addition, both groups demonstrated significantly improved quality of life at follow-up vs baseline, with no significant differences between groups. Serious adverse events were similar in both groups--none were definitely treatment-related. Intramuscular delivery of both Del-1 expressing plasmid and the control resulted in significant improvement in exercise capacity compared to baseline at 30, 90, and 180 days. There was no difference in outcome measures associated with the Del-1 plasmid.

Preservation of pelvic circulation with hypogastric artery bypass in endovascular repair of abdominal aortic aneurysm with bilateral iliac artery aneurysms

The endovascular repair (EVAR) of an abdominal aortic aneurysm (AAA) with a bilateral common iliac artery aneurysm (CIAA) often requires exclusion of the bilateral hypogastric artery (HA), which can be associated with pelvic ischemic complications such as erectile dysfunction and buttock claudication. This study assessed the effect of HA bypass on improving pelvic circulation. Five patients who underwent endovascular repair with HA bypass for an AAA with bilateral CIAA were evaluated. In all patients, the patency of the inferior mesenteric artery and bilateral HAs arteries was confirmed with preoperative computed tomography (CT) scans and angiography. During EVAR, penile blood flow was monitored with pulse-volume plethysmography measuring the penile brachial pressure index (PBI), and bilateral buttock blood flow was monitored with near-infrared spectroscopy measuring the gluteal tissue oxygenation index (TOI). An aortouni-external iliac artery stent graft with a crossover bypass was performed after embolization of the contralateral HA. HA bypass was performed between the crossover bypass graft and the ipsilateral HA via a retroperitoneal incision. Unilateral coil embolization of the contralateral side HA trunk slightly decreased blood flow to the contralateral side buttock but did not cause significant changes in penile blood flow. At the completion of EVAR, the levels of both PBI and the contralateral side TOI were significantly lower than the baseline levels. After ipsilateral side HA revascularization with HA bypass, both PBI and bilateral gluteal flow returned almost to the baseline levels. Postoperative angiography and CT scans demonstrated the patency of all HA bypasses and no endoleaks. None of the patients experienced new onset of erectile dysfunction or buttock claudication 1 month after surgery. Bilateral HA interruption during EVAR for AAA with bilateral CIAA was associated with significant depletion of both penile and gluteal blood flow. Intraoperative monitoring of PBI and TOI at the bilateral buttocks showed significant improvement of both parameters after HA bypass. HA bypass is an excellent procedure to improve pelvic circulation despite its increased surgical complexity.

The Novel Phosphodiesterase Inhibitor NM-702 Improves Claudication-Limited Exercise Performance in Patients With Peripheral Arterial Disease

The current study tested the hypothesis that NM-702 improves treadmill exercise performance in peripheral arterial disease patients with claudication-limited exercise performance. Patients with claudication experience significant disability, owing to their exercise limitation. Therapeutic options to improve exercise performance in these patients are limited. NM-702 is a novel drug that inhibits phosphodiesterase as well as thromboxane A2 synthase. This study was a randomized, multi-center, placebo-controlled, double-blind trial. Patients were randomized to receive 24 weeks of twice-daily treatment with either placebo (intent to treat population, n = 130), 4 mg NM-702 (n = 126), or 8 mg NM-702 (n = 130). After 24 weeks of treatment, 8 mg NM-702 was associated with a statistically significant increased peak walking time on a graded treadmill as compared with placebo (p = 0.004). Peak walking time after 24 weeks was increased by 17.1 +/- 49.0% in the placebo arm, 22.1 +/- 60.1% in the 4-mg NM-702 arm, and 28.1 +/- 50.5% in the 8-mg NM-702 arm. NM-702 at the 8-mg dose for 24 weeks was associated with statistically significant improvements in the treadmill claudication onset time as compared with placebo. In addition, as compared with placebo, NM-702 improved the physical component and physical functioning scores of the Medical Outcomes Study 36-Item Short Form and the walking distance and stair climbing domains of the Walking Impairment Questionnaire. NM-702 was generally well tolerated, but adverse events typical of vasodilators were common. NM-702 used for 24 weeks by patients with claudication was associated with improvements in laboratory- and ambulatory-based exercise performance.

Management of Lumbar Spinal Stenosis through the Use of Translatoric Manipulation and Lumbar Flexion Exercises: A Case Series

Lumbar spinal stenosis is a narrowing of the spinal canal or intervertebral foramen that can produce low back pain and leg pain and weakness. Surgical intervention is commonly performed to relieve these symptoms. Symptom reduction and longitudinal management of functional deficits with conservative care is less well documented. The purpose of this case series was to describe the outcomes of a conservative physical therapy program consisting of low- and high-velocity translatoric manipulations of T1-T9 and L1-L3, and two lumbar flexion exercises on 6 subjects diagnosed with lumbar spinal stenosis and neurogenic claudication. A treadmill test was repeated on a weekly basis and at discharge for each patient. All six subjects demonstrated improvements in treadmill walking time prior to the onset of neurogenic claudication (range: 1 min 34 sec to 26 min); in Oswestry Low Back Pain Disability Index scores (range: 7.5% to 64.7%); and in McGill Pain Questionnaire scores (range: 25% to 57%). Five subjects were measured using the Schober technique, and all showed improvement in thoracolumbar flexion mobility. Combined use of translatoric manipulation and spinal flexion exercises may have resulted in improved spinal flexibility, ambulatory abilities, and pain and functional status in six subjects with lumbar spinal stenosis.

Drug Treatment of Peripheral Arterial Disease in the Elderly

Peripheral arterial disease (PAD) may be asymptomatic, may be associated with intermittent claudication or may be associated with critical limb ischaemia. Coronary artery disease (CAD) and other atherosclerotic vascular disorders may coexist with PAD. Persons with PAD are at increased risk for all-cause mortality, cardiovascular mortality and mortality from CAD. Smoking should be stopped and hypertension, diabetes mellitus, dyslipidaemia and hypothyroidism treated. HMG-CoA reductase inhibitors (statins) reduce the incidence of intermittent claudication and improve exercise duration until the onset of intermittent claudication in persons with PAD and hypercholesterolaemia. Antiplatelet drugs such as aspirin or clopidogrel (especially the latter), ACE inhibitors and statins should be given to all persons with PAD. beta-Adrenoceptor antagonists should be given if CAD is present. The phosphodiesterase type 3 inhibitor cilostazol improves exercise time until intermittent claudication. Chelation therapy should be avoided. Correct implementation of medical therapy significantly reduces the excess mortality associated with PAD. In addition, medical therapy may result in significant improvements in walking ability that may obviate the need for lower extremity angioplasty with stenting and bypass surgery.

Daily Supplementation with (n-3) PUFAs, Oleic Acid, Folic Acid, and Vitamins B-6 and E Increases Pain-Free Walking Distance and Improves Risk Factors in Men with Peripheral Vascular Disease

A number of nutrients are known to be effective in preventing cardiovascular disease (CVD). We investigated the possible effects of a daily intake of low amounts of these nutrients on risk factors and clinical parameters in patients with peripheral vascular disease and intermittent claudication (PVD-IC). Male PVD-IC patients (n = 60) were randomly allocated into 2 groups. The supplement (S) group consumed 500 mL/d of a fortified dairy product containing eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), oleic acid, folic acid, and vitamins A, B-6, D, and E. The control (C) group consumed 500 mL/d of semiskimmed milk with added vitamins A and D. The patients received lifestyle and dietary recommendations, and they were instructed to consume the products in addition to their regular diet. Blood extractions and clinical explorations were performed after 0, 3, 6, 9, and 12 mo. Plasma concentrations of EPA, DHA, oleic acid, folic acid, and vitamins B-6 and E increased after treatment with supplements (P < 0.05). Plasma total cholesterol and ApoB concentrations decreased in the S group, and total homocysteine decreased in those patients with high initial concentrations. Walking distance before the onset of claudication increased in the S group (P < 0.001), and ankle-brachial pressure index values increased (P < 0.05). The inclusion in the everyday diet of certain nutrients known to promote cardiovascular health improved clinical outcomes while reducing a variety of risk factors in men with PVD-IC, providing new evidence of the potential role of nutrition in the reduction of PVD-IC symptoms.

Management of Peripheral Arterial Disease

Peripheral arterial disease (PAD) may be asymptomatic, may be associated with intermittent claudication, or may be associated with critical limb ischemia. Coronary artery disease (CAD) and other atherosclerotic vascular disorders may coexist with PAD. Persons with PAD are at increased risk for all-cause mortality, cardiovascular mortality, and mortality from CAD. Modifiable risk factors such as cessation of cigarette smoking and control of dyslipidemia, hypertension, and diabetes should be treated. Statins reduce the incidence of intermittent claudication and improve exercise duration until the onset of intermittent claudication in persons with PAD and hypercholesterolemia. Antiplatelet drugs such as aspirin or clopidogrel, especially clopidogrel, and angiotensin-converting enzyme inhibitors should be given to all persons with PAD. beta-Blockers should be given if CAD is present. Exercise rehabilitation programs and cilostazol improve exercise time until intermittent claudication. Indications for lower-extremity angioplasty, preferably with stenting, or bypass surgery are 1) incapacitating claudication in persons interfering with work or lifestyle; 2) limb salvage in persons with limb-threatening ischemia as manifested by rest pain, nonhealing ulcers, and/or infection or gangrene; and 3) vasculogenic impotence. However, amputation should be performed if tissue loss has progressed beyond the point of salvage, if surgery is too risky, if life expectancy is very low, or if functional limitations diminish the benefit of limb salvage.

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

The authors conducted a study to investigate the effect of simvastatin after 6 months and 1 year on the time to onset of intermittent claudication during treadmill exercise in patients with peripheral arterial disease. Thirty-four patients were randomized to simvastatin, 35 were randomized to placebo. Simvastatin therapy resulted in a 24% increased treadmill exercise time until onset of intermittent claudication from baseline at 6 months and by 42% at 1 year.

β-Adrenergic Blocking Agents and Intermittent Claudication: Systematic Review

To clarify contradictions in past reports and the package inserts for beta-adrenergic blocking agents (beta-blockers) for patients with intermittent claudication (IC), we investigated the effects of beta-blockers in patients with IC using the systematic review technique. Data sources were randomized, controlled trials that investigated the effects of beta-blockers compared with the placebo or untreated group (controls) in patients with IC. Primary endpoints were walking distance and walking time, and secondary endpoints were ankle-brachial index (ABI) and calf blood flow. Nine trials were included in the analysis. Meta-analysis showed that there was a significant worsening in maximal walking distance and initial claudication distance in patients receiving beta-blockers, with standardized mean differences of -0.31 and -0.39 (95% confidence interval -0.58 to -0.04 and -0.73 to -0.06, P=0.03 and 0.02, respectively) compared with controls. There were no significant differences in maximal walking time (0.07, -0.24 to 0.37), time to onset of claudication (0.12, -0.23 to 0.47), ABI at rest (0.24, -0.30 to 0.78), calf blood flow at rest (0.00, -0.26 to 0.25), and calf blood flow after exercise (-0.23, -0.69 to 0.22). However, only one trial evaluated ABI, and the number of cases is increasing, suggesting that beta-blockers do not worsen ABI. There was no evidence that beta-blockers prescribed for patients with IC have unsuitable "precautions" in the package inserts. However, reluctance to administer beta-blockers to patients because they have IC is not appropriate.