Focus on Alternative and Complementary Therapies
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Focus Alternat Complement Ther©2005 Pharmaceutical Press
Focus Altern Complement Ther 2004; 9: 93–5
Peripheral arterial disease affects a considerable proportion of the general population. Most commonly its cause is atherosclerosis, which explains the high rates of co-morbidity with coronary heart disease and cerebrovascular disease. Peripheral arterial disease is a potential threat to functional independence, particularly in the elderly, and is associated with hospitalisation, surgery and death.1,2 The incidence of one of its early symptoms – intermittent claudication – increases sharply with age.3–6 Between the ages of 45 and 54 years the annual incidence of intermittent claudication is about 7 to 19 cases per 10 000 individuals, increasing to 54 to 61 cases per 10 000 between the ages of 65 and 74 years.4 Treatment is usually conservative7 and largely consists of regular physical exercise and pharmacological interventions with, for instance, cilostazol.8–11 The aim of this focus article is to assess the effectiveness of complementary treatment options for peripheral arterial disease based on the evidence from systematic reviews, meta-analysis and rigorous clinical trials.
Systematic literature searches were conducted in Medline, Embase, Amed and the Cochrane Library. The search terms used were ‘alternative medicine’, ‘complementary medicine’, ‘peripheral arterial disease’, ‘arterial occlusive disease’, ‘intermittent claudication’ and ‘atherosclerosis’. Each database was searched from its inception until November 2003. Hand-searches were performed by searching the bibliographies of all located papers. No restrictions regarding the language of publication were imposed. Studies assessing the effects of complementary treatments on the risk factors of peripheral arterial disease (e.g. hypercholesterolaemia, diabetes and hypertension) were excluded.
The results indicate positive evidence for the herbal dietary supplements Allium sativum (garlic), Ginkgo biloba (ginkgo) and Padma 28, for the non-herbal dietary supplement vitamin E, and for chelation therapy, subcutaneous CO2 insufflation and CO2 baths.
A Cochrane review12 (updated April 2003) of the use of Allium sativum for treating intermittent claudication identified one RCT. This trial was double-blind and placebo-controlled, and included 78 patients (age range 40–75 years) who were treated with 800 mg garlic extract daily for 12 weeks. All patients additionally received physical therapy twice weekly. The authors of the trial report a significant increase in painfree walking distance compared with placebo. The Cochrane reviewers report, however, that based on their own data analysis, which seems flawed, there is no statistically significant intergroup difference. Despite this analysis their conclusion that further trials are needed remains.
The effectiveness of Ginkgo biloba extract for treating intermittent claudication was assessed in a meta-analysis.13 Only RCTs that were double-blind and placebo-controlled were included. Twelve trials were identified, of which eight met all the inclusion criteria (n = 415). The common outcome measure in all eight trials was the painfree walking distance. Statistical pooling of these data suggested a significant beneficial effect in favour of G. biloba compared with placebo (weighted mean difference 34 m, 95% CI 26–43). Subgroup analysis of studies using similar methodological features (ergometer speed 3 km/h, inclination 12%) suggested a difference of 33 m (95% CI 22–43) in favour of G. biloba. Six trials also assessed maximal walking distance. All of these trials report a significant increase compared with placebo. The increase in maximal walking distance ranged between 36 and 189 m compared with placebo. Thus, according to these data G. biloba extract is effective over and above placebo for patients with intermittent claudication.
Padma 28 is a Tibetan herbal mixture containing 22 different ingredients. Four double-blind, placebo-controlled RCTs were identified that tested Padma 28 in patients with intermittent claudication. Patients were treated with 1.4–2.3 g daily for 4–16 weeks.14–17 The maximal walking distance was evaluated in all studies. While three trials reported significant differences in maximal walking distance in patients treated with Padma 28 compared with placebo, the fourth reported an increase compared with baseline. Overall the available data suggest that this herbal mixture is a promising option for patients with intermittent claudication. However, more data from rigorous clinical trials are required.
A Cochrane review (updated February 2001) assessed the evidence of vitamin E for intermittent claudication.18 It identified five controlled trials of which two were described as double-blind RCTs. In total, 265 patients were treated with 0.3–1.6 g for a period of 12 weeks to 18 months. The reviewed studies were of short treatment duration and of poor quality, according to the reviewers. All of the studies report positive effects regarding their primary endpoints. The meta-analysis of two studies suggests a favourable effect (RR 0.6, 95% CI 0.3–1.2). The authors conclude that there is insufficient evidence to determine whether or not vitamin E is an effective treatment for intermittent claudication.
Chelation therapy uses oral and intravenous administration of ethylene diamine tetracetic acid (EDTA), usually in combination with vitamins and trace elements, to treat a variety of conditions. including peripheral arterial disease. A systematic review19 of double-blind, placebo-controlled studies identified four trials (n = 225). Over a period of 5–20 weeks, 1.5–3.0 g Na2 EDTA or isotonic NaCl as the control intervention were administered. None of the three studies that measured painfree walking distance reported a significant difference compared with placebo. It was concluded that chelation therapy is not superior to placebo for peripheral arterial disease. This is corroborated by a more recent review20 and a Cochrane review.21
Subcutaneous carbon dioxide (CO2) insufflation is a therapy mainly practised in continental Europe. The local CO2 emphysema produces reddening of the skin and increased blood flow, which may be beneficial for patients with intermittent claudication. A systematic review identified three RCTs for this condition.22 While patients in the treatment group received subcutaneous insufflation of 100–450 ml CO2 daily for 3–5 weeks, patients in the control groups were either on a waiting list or bathed in CO2-containing water. One trial reported significant intergroup differences for painfree walking distance compared with waiting list controls, while another trial reported intergroup differences compared with waiting list controls for walking distance that was not more closely defined (p not reported). Hence there are few data from RCTs to suggest that subcutaneous CO2 insufflation is effective beyond reasonable doubt for patients with intermittent claudication.
A small RCT (n = 24) assessed the effects of baths in water containing CO2.23 Patients were treated daily for 30 min, five times weekly for a period of 4 weeks. The CO2 concentration of the water was 1 g/kg. The study reports an increase in painfree walking distance and transcutaneous O2 partial pressure at the foot compared with baseline. Differences compared with baths in fresh water, which was the control intervention, were not reported.
The available data from systematic reviews, meta-analyses and rigorous clinical trials suggest that G. biloba is effective for patients with peripheral arterial disease in Fontaine stage II (intermittent claudication). Promising data are available for Padma 28, which seems to be of some benefit for this condition. For all other complementary treatment options there is no evidence beyond reasonable doubt to suggest effectiveness for patients with peripheral arterial disease.
