De Backer T L, Vander Stichele R H, Bogaert M G
Heymans Institute of Pharmacology - Medical School, University of Gent, De Pintelaan 185, Gent, Belgium, B-9000.
Cochrane Database Syst Rev. 2001(1):CD000988. doi: 10.1002/14651858.CD000988.
Intermittent claudication 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 claimed to have beneficial effects on the microcirculation. It is used chiefly to treat peripheral vascular disease and to a lesser extent for cerebrovascular arterial disease. However, its clinical efficacy for intermittent claudication has not yet been critically examined.
To evaluate the available evidence on the efficacy of buflomedil for intermittent claudication.
We searched Medline, International Pharmaceutical Abstracts (IPA) and the Cochrane Controlled Trials Register. Abbott Laboratories, the distributor of buflomedil, was asked to provide reports of controlled clinical trials. Reference lists of retrieved articles were checked, and enquiries sent to authors of known trials, to identify additional trials. Finally, we conducted a Science Citation Index search.
Trial reports had to be double-blinded, randomized, and conformed to our PIO-criteria (Patients, Intervention, Outcome) to be considered for inclusion. Patients were required to have proven intermittent claudication (Fontaine stage II); the intervention was to be oral administration of buflomedil compared to placebo; and outcomes had to include pain-free walking distance (PFWD) and maximum walking distance (MWD) analysed by standardized exercise test.
Searches of bibliographic databases yielded three eligible randomized controlled trials (RCTs) and a meta-analysis referring to nine eligible trials. Two of these nine trials had already been identified; two had been published in journals not referenced in traditional bibliographic indexes; and five were unpublished. Despite multiple requests, only one of the five unpublished trials was provided by the author of the meta-analysis, the other four could not be retrieved. Four of the six eligible trials retrieved were subsequently excluded after quality evaluation. Data on walking distances were extracted from the two remaining trials. Differences in incremental gain between active and placebo groups for PFWD and MWD with their confidence intervals were calculated.
Both RCTs showed moderate improvements in PFWD for patients on buflomedil. In one trial this improvement (75 m, 95% CI 37-114) was statistically significant, but in the other, with a wholly diabetic population, it was non-significant (81m, 95% CI -9-170) compared to placebo. For both RCTs the gains in MWD were statistically significant, but with wide confidence intervals (81 m, 95% CI 30-131; and 171 m, 95% CI 27-316 respectively). Pooling of the data was not attempted.
REVIEWER'S CONCLUSIONS: There is little evidence available to evaluate the efficacy of buflomedil for intermittent claudication. Most available trials are of poor quality and were excluded. The two trials included showed moderately positive results but these are undermined by publication bias since we know of another four unpublished, irretrievable, and inconclusive studies. There is a lack evidence for the efficacy of buflomedil in intermittent claudication.
间歇性跛行是由慢性闭塞性动脉疾病引起的疼痛，在运动期间肢体出现，休息后缓解。丁咯地尔是一种血管活性药物，据称对微循环有有益作用。它主要用于治疗周围血管疾病，在较小程度上用于治疗脑血管动脉疾病。然而，其对间歇性跛行的临床疗效尚未得到严格检验。
评估丁咯地尔治疗间歇性跛行疗效的现有证据。
我们检索了Medline、国际药学文摘（IPA）和Cochrane对照试验注册库。丁咯地尔的经销商雅培实验室被要求提供对照临床试验报告。检查了检索到的文章的参考文献列表，并向已知试验的作者进行询问，以识别其他试验。最后，我们进行了科学引文索引检索。
试验报告必须是双盲、随机的，并符合我们的PIO标准（患者、干预、结果）才能考虑纳入。患者必须已证实患有间歇性跛行（Fontaine II期）；干预措施是口服丁咯地尔与安慰剂进行比较；结果必须包括通过标准化运动试验分析的无痛步行距离（PFWD）和最大步行距离（MWD）。
对文献数据库的检索产生了三项符合条件的随机对照试验（RCT）和一项涉及九项符合条件试验的荟萃分析。这九项试验中的两项已经被识别；两项发表在传统文献索引未引用的期刊上；五项未发表。尽管多次请求，荟萃分析的作者仅提供了五项未发表试验中的一项，其他四项无法检索到。在质量评估后，检索到的六项符合条件的试验中有四项随后被排除。从其余两项试验中提取了步行距离数据。计算了活性组和安慰剂组在PFWD和MWD方面的增量增益差异及其置信区间。
两项RCT均显示服用丁咯地尔的患者PFWD有中度改善。在一项试验中，这种改善（75米，95%置信区间37 - 114）具有统计学意义，但在另一项全是糖尿病患者的试验中，与安慰剂相比无统计学意义（81米，95%置信区间 - 9 - 170）。对于两项RCT，MWD的增加均具有统计学意义，但置信区间较宽（分别为81米，95%置信区间30 - 131；和171米，95%置信区间27 - 316）。未尝试对数据进行合并。
几乎没有证据可用于评估丁咯地尔治疗间歇性跛行的疗效。大多数现有试验质量较差并被排除。纳入的两项试验显示出中度阳性结果，但由于我们知道另外四项未发表、无法检索且无结论的研究，这些结果受到发表偏倚的影响。缺乏丁咯地尔治疗间歇性跛行疗效的证据。
