Interventions in the management of serum lipids for preventing stroke recurrence.
BACKGROUND
A close association between serum lipid levels and the incidence of coronary heart disease (CHD) has been well proven in middle aged and older persons, up to the age of 70-75 years. Individual studies have shown interventions to reduce total and low density lipoprotein (LDL) cholesterol levels, especially with 3-hydroxy-3-methylglutaryl coenzyme a (HMG-CoA) reductase inhibitors (statins), to be of benefit in reducing CHD and stroke events in those with a history of coronary heart disease. However, the relation of serum cholesterol and cholesterol sub-fractions with cerebrovascular disease is less clear. It is unclear whether lipid levels in the post-stroke period are a predictor of recurrence and whether treatment to alter levels can prevent recurrence of either stroke or cardiovascular events.


OBJECTIVE
To investigate the effect of altering serum lipids in the prevention of cardiovascular disease and stroke recurrence in subjects with a history of stroke.


METHODS
The Cochrane Group Trials Register was searched up to 8 May 2001 along with MEDLINE (from 1966), EMBASE (from 1980) and the Cochrane Controlled Trials Register. All pharmaceutical firms known to produce a lipid lowering agent were also contacted and asked to provide information on publications or unpublished work relevant to this review.


METHODS
This review included unconfounded randomised trials of subjects aged 18 years and over with a history of stroke or Transient Ischaemic Attack (TIA).


METHODS
The data were extracted independently by the three reviewers. MetaView 4.1 was used for all statistical analyses.


RESULTS
Five studies involving 1700 patients were included in the review. The active intervention in two of the studies was Clofibrate, Pravastatin in another two and Conjugated Oestrogen in the fifth. Fixed effects analysis showed no evidence of a difference in stroke recurrence between the treatment and placebo groups for those with a previous history of stroke or TIA (odds ratio 0.96, 95% confidence interval 0.71 to 1.30). In addition there was also no evidence, based on two studies, that intervention reduced the odds of all cause mortality (odds ratio 0.87, 95% confidence interval 0.55 to 1.39) nor, from one study, that there was any effect on subsequent vascular events (odds ratio 1.27, 95% confidence interval 0.84 to 1.89).


CONCLUSIONS
These trials do not provide evidence for a benefit, or harm, from interventions to alter serum lipid levels in patients with a history solely of cerebrovascular disease. Their use, therefore, cannot yet be recommended routinely in this patient group, but ischaemic stroke patients with a history of myocardial infarction should receive statin therapy along the lines of the previous recommendations for those patients with a history of myocardial ischaemia. There are currently three ongoing trials which will recruit approximately 30,000 patients, including those with a history of stroke, and the results of these trials may have a significant effect on these conclusions.
Manktelow
B
B
Dept. Epidemiology and Public Health, University of Leicester, 22-28 Princess Road West, Leicester, UK, LE1 6TP. bm18@le.ac.uk
Gillies
C
C
Potter
J F
JF
D002318:Cardiovascular Diseases / Q000517:prevention & control; D002994:Clofibrate / Q000627:therapeutic use; D004966:Estrogens, Conjugated (USP) / Q000627:therapeutic use; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D017035:Pravastatin / Q000627:therapeutic use; D012008:Recurrence; D020521:Stroke / Q000517:prevention & control*
D004966:Estrogens, Conjugated (USP); D000960:Hypolipidemic Agents; D002994:Clofibrate; D017035:Pravastatin