Review question
We reviewed the evidence about the effect of buflomedil on death, disability, and neurological functions in people with acute ischaemic stroke.
Background
Buflomedil has been used for people with diseases of the leg arteries and has shown some benefits for people with a previous stroke. The most common type of stroke is due to narrowing or blockage of an artery in the brain (i.e. ischaemic stroke). Buflomedil is a drug that can dilate brain blood vessels, which may have benefit for people with ischaemic stroke. However, it has not been approved to treat stroke in clinical practice. We wanted to discover whether buflomedil is effective and safe to treat people within the first few days after the onset of their ischaemic stroke.
Study characteristics
The evidence is current to September 2014. We found 26 randomised controlled trials with 2756 participants. All these trials were conducted in China with adult stroke patients of both sexes. All participants were in hospital and within the first few days after the onset of their stroke. Most trials delivered buflomedil intravenously, with a daily dose of 200 mg for 14 days.
Key results
There was insufficient evidence to show whether buflomedil reduced the chance of dying or having less long-term disability in stroke survivors. Although all trials assessed outcomes immediately at the end of treatment, there was no robust evidence on the effects of buflomedil on any short-term outcomes. Also, there was insufficient evidence on the harms that the drug might cause.
Quality of evidence
The quality of evidence was generally low. There were not enough data and most trials had poor study design or incomplete reporting of relevant information. To provide evidence for the use of buflomedil as a routine treatment for acute ischaemic stroke, high quality randomised trials are needed.
There is insufficient evidence on the efficacy or safety of buflomedil to support its use for the treatment of acute ischaemic stroke. Given these uncertainties, the data support the rationale for an adequately powered RCT of buflomedil in people with acute ischaemic stroke.
Few strategies are effective for the treatment of acute ischaemic stroke. Buflomedil is a vasoactive agent that has been used for peripheral arterial diseases. Research studies have suggested that buflomedil may have beneficial effects in people with cerebral vascular diseases, including acute ischaemic stroke, however it has not been approved for treating stroke in clinical practice.
To assess the efficacy and safety of buflomedil for the treatment of acute ischaemic stroke.
We searched the Cochrane Stroke Group Trials Register (September 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 4), MEDLINE (1950 to February 2014), EMBASE (1980 to February 2014), ProQuest Dissertations and Theses Database (July 2014), Web of Science (including Conference Proceedings Citation Index Science (CPCI-S)) (July 2014), and four Chinese databases (February 2014). We also searched five ongoing trials registers and reference lists of the included trials.
We included randomised controlled trials (RCTs) that investigated the efficacy of buflomedil in people with acute ischaemic stroke. The primary outcome of this review was long-term death or disability/dependence. Other outcomes included short-term death, short-term disability, neurological deficits, and adverse events. We included trials comparing buflomedil versus a placebo control, trials comparing buflomedil plus usual medical care versus usual medical care alone, or those comparing buflomedil plus another intervention versus that intervention alone. We excluded trials comparing buflomedil alone with other potentially active intervention(s).
Two review authors independently scrutinised citations, selected studies, extracted data and assessed risk of bias in the included trials. We reported risk ratios (RRs) for dichotomous data and standardised mean differences (SMDs) for continuous data. We performed meta-analysis, using a random-effects model, for death and improvement of neurological deficits. Data for disability/dependence and adverse events were not suitable for meta-analysis thus we reported these narratively. We performed subgroup analyses for time of recruitment since stroke, delivery route, daily dose, and treatment duration.
We included 26 trials (2756 participants), all conducted in China. All participants were inpatients within the first few days after stroke onset (mean age 58 to 75 years and male proportion 45% to 80%). Most trials delivered buflomedil intravenously, with a daily dose of 200 mg for 14 days. The study quality was generally poor and many trials were poorly reported.
Only one trial reported long-term death and disability, where stroke survivors in the buflomedil group had a lower risk of suffering 'death or disability' than those in the control group (200 participants, RR 0.71, 95% confidence interval (CI) 0.53 to 0.94). All 26 trials assessed outcomes by the end of treatment (eight trials with 1056 participants reported death, one trial with 85 participants reported disability, and 26 trials with 2756 participants reported neurological deficits), but there was no robust evidence for any of these short-term outcomes. Seventeen trials (1899 participants) investigated the presence of adverse events during the treatment, of which six trials (853 participants) reported "no significant adverse event in any participants" and the other 11 trials (1046 participants) reported a total of 38 adverse events in the buflomedil group and two events in the control group. In general, for each of these outcomes the quality of evidence was low according to the GRADE principles.