Cerebral vasospasm and related delayed ischaemic deficits (DIDs) occur in about 17% to 40% of patients with aneurysmal subarachnoid haemorrhage (SAH) and lead to a poor outcome. Cholesterol-reducing agents might improve unfavourable outcomes.
To assess the effects of cholesterol-reducing agents for improving outcomes in patients with aneurysmal SAH.
We searched the Cochrane Stroke Group Trials Register (May 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 5), MEDLINE (1948 to May 2012) and EMBASE (1980 to May 2012). We also searched three Chinese databases: SinoMed, CNKI and VIP (May 2012). In an effort to identify further published, ongoing and unpublished trials we searched relevant clinical trials and research registers (May 2012), contacted pharmaceutical companies and investigators known to be involved in previous trials and screened the reference lists of all relevant articles identified.
We included randomised controlled trials (RCTs) that compared cholesterol-reducing agents with control or placebo treatment in participants with aneurysmal SAH.
Data collection and analysis
Two review authors independently applied the inclusion criteria, reviewed the relevant trials and extracted data. We did not perform meta-analysis as we only included one RCT in the review.
We included one study in which 39 patients received either simvastatin (80 mg daily; n = 19) or placebo (n = 20) for 14 days. The incidence of DIDs (secondary outcome) was 26% (5/19) in the simvastatin group versus 60% (12/20) in the placebo group (risk ratio (RR) 0.44, 95% confidence interval (CI) 0.19 to 1.01, P = 0.05). This means that, in this study, simvastatin had no effect on DIDs. Two patients in the simvastatin group and one patient in the placebo group had elevated levels of aspartate transaminase or alanine transaminase. One patient in the simvastatin group had a raised creatine phosphokinase. There were no results from this trial for the primary outcome of death or dependency at six months.
We cannot draw any conclusions about the effectiveness and safety of lowering cholesterol in aneurysmal SAH because of insufficient reliable evidence from only one small trial. More RCTs are needed.
Plain language summary
Cholesterol-reducing drugs for brain haemorrhage (subarachnoid haemorrhage)
Subarachnoid haemorrhage (SAH) is a serious condition where bleeding occurs over the surface of the brain. This bleeding usually comes from an abnormality (aneurysm) in one of the blood vessels on the brain surface. In addition to the damage caused by the initial bleeding, people with SAH often suffer a later reduction in blood flow to the brain and hence additional delayed brain injury. It has been proposed that cholesterol-reducing drugs may reduce this delayed brain injury. This review found only one small trial of 39 participants. Cholesterol-reducing drugs did not reduce the risk of delayed brain injury and did not significantly improve participants’ degree of recovery. There were no significant differences in adverse events. This review is based on one small trial and no reliable conclusions can be drawn at present.