This review assessed the effects of statins on stroke. The authors concluded that statins reduce low-density lipoprotein cholesterol and may reduce the incidence of any type of stroke. Given that the review methods and study quality were not reported, and that the search for individual studies was limited, it is difficult to comment on the strength of the evidence underpinning the authors' conclusions.

The primary objective was to assess the effects of statins on stroke incidence and mortality. The secondary objectives were to investigate the effect of statins on haemorrhagic stroke and the relationship between low-density lipoprotein cholesterol (LDL-C) reduction and the incidence of stroke.

PubMed was searched to August 2003 for RCTs and reviews; the keywords were reported. The reference lists in identified studies were checked.

Study designs of evaluations included in the review

Randomised controlled trials (RCTs) were eligible for inclusion.

Specific interventions included in the review

Studies that compared statins with a control (placebo or usual care) were eligible for inclusion. Studies of primary or secondary prevention of coronary artery disease that used uni- or multifactorial interventions were also eligible. The included studies used various statins (details were reported). The mean duration of follow-up in the included studies ranged from 0.3 to 6.1 years. The review indicated that some studies used statins in the control group, but no details were reported.

Participants included in the review

Inclusion criteria were not specified in terms of the participants. The mean age of the participants in the included studies ranged from 53 to 75 years, and the proportion of males ranged from 48 to 100%.

Outcomes assessed in the review

Studies that reported stroke events (brain infarction of haemorrhage) analysed on an intention-to-treat basis were eligible for inclusion. The review did not assess transient ischaemic attacks. The review also assessed the change in LDL-C and carotid artery intima-media thickness (IMT).

How were decisions on the relevance of primary studies made?

The authors did not state how the papers were selected for the review, or how many reviewers performed the selection.

The authors did not state that they assessed validity.

The data were extracted on an intention-to-treat basis. The authors did not state how many reviewers performed the data extraction. For each study, odds ratios (ORs) of events with 95% confidence intervals (CIs) were calculated.

How were the studies combined?

The studies were combined using meta-analysis. Studies with no events in either treatment group were excluded from the meta-analyses. A value of 0.25 was added to cells with zero events in one treatment group. Pooled ORs with 95% CIs were calculated using a fixed-effect model (Mantel-Haenszel). The possibility of publication bias was explored using a funnel plot for all strokes and was tested using Egger's statistic.

How were differences between studies investigated?

Statistical heterogeneity was assessed using the Breslow-Day statistic. The correlations between LDL-C reduction and stroke and LDL-C and IMT were estimated. Logistic regression was used to explore the relationship between changes in LDL-C and firstly the log-OR for stroke (weighted by the inverse of the variance), and secondly with IMT (weighted by the sample size). A sensitivity analysis was performed after first excluding studies in which stroke was not a pre-specified secondary outcome, and secondly by including one RCT with unsuccessful randomisation.

Twenty-seven RCTs (n=97,981) were included. Twenty-six of these RCTs were included in the meta-analyses as one RCT (n=3,853) was unsuccessfully randomised.

Statins significantly reduced stroke incidence compared with the control; the OR was 0.79 (95% CI: 0.73, 0.85). No statistically significant heterogeneity was found (P=0.35). The results were similar after excluding studies in which stroke was not a pre-specified outcome, and after including one RCT with unsuccessful randomisation.

Statins reduced fatal strokes by 9% compared with the control, but the reduction was not statistically significant; the OR (15 RCTs) was 0.91 (95% CI: 0.76, 1.10). No statistically significant heterogeneity was found (P=0.71).

There was no statistically significant difference in haemorrhagic stroke between statins and control; the OR (8 RCTs) was 0.90 (95% CI: 0.65, 1.22). No statistically significant heterogeneity was found (P=0.15). The results were similar after including one RCT with unsuccessful randomisation.

The reduction in LDL-C ranged from about 11 to 52% among studies. There was a significant correlation (r) between LDL-C reduction and stroke (r=0.58, P=0.002) and between LDL-C reduction and IMT (r=0.65, P=0.004).

Each 10% reduction in LDL-C reduced the risk of any type of stroke by 15.6% (95% CI: 6.7, 23.6) and reduced carotid IMT by 0.73% (95% CI: 0.27, 1.19).

The asymmetry of the funnel plot and results from Egger's analysis (P=0.056) suggested the presence of publication bias.

Statins may reduce the risk of any type of stroke without increasing the risk of haemorrhagic stroke. This reduction appears to be largely due to the reduction in LDL-C.

The review question was clear in terms of the study design, intervention and outcomes. Inclusion criteria for the participants were not reported. Only one database was searched and this might have resulted in the omission of other relevant studies. It was unclear whether any language limitations had been applied. No attempts were made to locate unpublished studies, thus raising the possibility of publication bias; this possibility was confirmed by the funnel plot and statistical tests. The methods used to select studies and extract the data were not described, so it is not known whether any efforts were made to reduce errors and bias. Only RCTs were included but the quality of the included studies was not assessed.

Statistical heterogeneity was assessed and the studies were appropriately combined in a meta-analysis. Appropriate graphs were presented for the examination of the relationship between LDL-C and stroke and IMT change. Given the limited search strategy and the fact that the quality of the included studies and the methods used to conduct the review were not reported, it is difficult to comment on the strength of the evidence underpinning the authors' conclusions.

The authors did not state any implications for practice or further research.

Public, academic and institutional sources (PHRC AOA98004, SOS-ATTAQUE CEREBRALE Association); Formation de Recherche en Neurologie Vasculaire (Association Claude Bernard).

Lavalee P, Labreuche J, Touboul PJ, Amarenco P. Statines en prevention des accidents vasculaires cerebraux et de l'atherosclerose carotidienne: meta-analyse. Rev Neurol (Paris) 2005;161 Suppl 1:1S26-27.

This additional published commentary may also be of interest. Claiborne Johnston S. Review: statins reduce stroke but not stroke mortality. Evid Based Med 2005;10:73.

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.