T L M de Backer1, M Bogaert, R Vander Stichele. 1. Ghent University, Heymans Institute of Pharmacology, De Pintelaan 185, Gent, Belgium, B-9000. tine.debacker@ugent.be
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 STRATEGY: 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showed moderately positive results; these are undermined by publication bias since we know of at least another four unpublished, irretrievable, and inconclusive studies.Buflomedil's benefit is small in relation to safety issues and its narrow therapeutic range.
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 STRATEGY: 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.