Buflomedil for intermittent claudication
Abstract
Background
Intermittent claudication (IC) is pain caused by chronic occlusive arterial disease, that develops in a limb during exercise and is relieved with rest. Buflomedil is a vasoactive agent used to treat peripheral vascular disease. However, its clinical efficacy for IC has not yet been critically examined.
Objectives
To evaluate the available evidence on the efficacy of buflomedil for IC.
Search methods
We searched the specialized trials register of the Cochrane Peripheral Vascular Diseases Review Group (last searched August 2007), the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Issue 3, 2007), MEDLINE (1966 to August 2007), International Pharmaceutical Abstracts (IPA) (from inception to August 2007), Science Citation Index (from inception to August 2007). We contacted Abbott Laboratories (buflomedil distributor) for controlled clinical trial data and approached authors for additional trial information.
Selection criteria
Double‐blinded, randomized controlled trials (RCTs) in patients with IC (Fontaine stage II) receiving oral buflomedil compared to placebo. Pain‐free walking distance (PFWD) and maximum walking distance (MWD) were analysed by standardized exercise test.
Data collection and analysis
Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information.
Main results
We included two RCTS with 127 participants. Both RCTs showed moderate improvements in PFWD for patients on buflomedil. This improvement was statistically significant for both trials (WMD 75.1 m, 95% confidence interval (CI) 20.6 to 129.6; WMD 80.6 m, 95% CI 3.0 to 158.2), the latter being a wholly diabetic population. For both RCTs, MWD gains were statistically significant with wide confidence intervals (WMD 80.7 m, 95% CI 9.4 to 152; WMD 171.4 m, 95% CI 51.3 to 291.5), respectively.
Authors' conclusions
There is little evidence available to evaluate the efficacy of buflomedil for IC. Most trials were excluded due to poor quality. The two included trials showed moderately positive results; these are undermined by publication bias since we know of at least another four unpublished, irretrievable, and inconclusive studies.
Buflomedil's benefit is small in relation to safety issues and its narrow therapeutic range.
PICOs
Plain language summary
Buflomedil for intermittent claudication
Intermittent claudication (IC) is pain that develops in a limb (mostly calves and thighs) during exercise and is relieved with rest. It is caused by insufficient blood flow due to peripheral arterial occlusive disease.
Treatment should contain all measures of secondary prevention of cardiovascular diseases. Regular exercise and smoking cessation is the most effective therapy to improve the symptoms of claudication. Drug treatments include vasoactive agents to improve blood flow (such as vasodilators and other hemorheologic agents that reduce blood viscosity), anticoagulants, antiplatelet agents and lipid lowering agents. Only a minority of patients undergo angioplasty or vascular surgery.
Buflomedil is a vasoactive agent widely used to treat intermittent claudication. The review authors included six trials but could not use four of them because of the methodologies used and high risk of bias. The two remaining controlled trials randomised a total of 127 participants to receive buflomedil or placebo for at least three months. One of these trials involved 40 participants with diabetes. Taken together, the trials showed moderately positive results for improvements in pain‐free walking distance on a treadmill (76.9 m, 95% CI 32.3 to 121.5) and maximum walking distance (112.6 m, 95% 27.7 to 197.5) with buflomedil for 12 weeks, showing a wide variation in benefit between participants.
The four excluded studies consisted of three small marginally positive studies and one larger negative study. At least another four unpublished studies could not be retrieved and were reported to have inconclusive results.
Recent safety concerns have been raised about buflomedil because of lethal and non‐lethal neurologic and cardiovascular advents events in cases of accidental and voluntary overdoses.
The benefit of buflomedil is small in light of relatively little evidence on efficacy and narrow therapeutic range along with recent safety issues.
