Elsevier

The Lancet Neurology

Volume 8, Issue 5, May 2009, Pages 453-463
The Lancet Neurology

Review
Lipid management in the prevention of stroke: review and updated meta-analysis of statins for stroke prevention

https://doi.org/10.1016/S1474-4422(09)70058-4Get rights and content

Summary

Despite the inconsistent or weak association between cholesterol and stroke, lowering of cholesterol concentrations with statins reduces the risk of stroke in high-risk populations and in patients with non-cardioembolic stroke or transient ischaemic attack. Statin therapy is the most important advance in stroke prevention since the introduction of aspirin and antihypertensive treatments. Meta-analysis of randomised trials of statins in combination with other preventive strategies, including 165 792 individuals, shows that each 1 mmol/L (39 mg/dL) decrease in LDL cholesterol equates to a reduction in relative risk for stroke of 21·1% (95% CI 6·3–33·5, p=0·009). In secondary prevention of non-cardioembolic stroke, intense reduction of LDL cholesterol by statins also significantly reduced the risk of recurrent stroke (relative risk 0·84, 0·71–0·99, p=0·03) and major cardiovascular events (0·80, 0·69–0·92, p=0·002). Future directions include assessment of a target LDL cholesterol concentration of less than 1·8 mmol/L (70 mg/dL), the effects of triglyceride-lowering therapy alone or in combination with statins, and the effects of treatments to raise HDL cholesterol concentrations.

Introduction

Despite the inconsistent or weak association between cholesterol and stroke, a decrease in cholesterol concentrations with statins can reduce the incidence of stroke in high-risk populations1 and in patients with a stroke or transient ischaemic attack.2 Statin therapy has become the most important advance in stroke prevention since the introduction of aspirin and blood pressure-lowering therapies. In combination with other preventive strategies, such as blood pressure-lowering and antithrombotic treatment, a 1 mmol/L decrease in LDL cholesterol concentrations can substantially decrease stroke incidence.1 Statins not only lower the overall risk of stroke but also slow the progression of carotid atherosclerosis,3 reduce inflammation and endothelial dysfunction, decrease platelet aggregation to improve fibrinolysis, lower blood pressure, and decrease the risk of thromboembolic complications to the brain by reducing the incidence of myocardial infarction. Statins might also have a neuroprotective effect.4, 5, 6 Other lipid-modifying drugs have been less successful in reducing the incidence of stroke;7, 8 however, because of the strong rationale for use of triglyceride-lowering drugs and treatments that raise concentrations of HDL cholesterol in patients with stroke, further investigation of these possible treatments is needed. In this Review, we outline the epidemiology of lipids and risk of stroke and discuss the evidence for decreasing lipid concentrations in patients who are at high risk of stroke or have had a previous stroke. Finally, we offer suggestions for possible avenues for future research.

Section snippets

Lipids and stroke

The Prospective Study Collaboration group did a meta-analysis of data from 45 observational cohorts that included 450 000 individuals,9 in which 13 397 fatal strokes were reported during an average follow-up of 16 years. No association between total cholesterol concentration and risk of fatal stroke was found. In a further meta-analysis of almost 1 million individuals, the collaboration found a clear association between total serum concentration of cholesterol and risk of fatal myocardial

Search strategy and selection criteria

For this Review, we updated our previous meta-analysis, which identified references from January, 1966, to August, 2003. References for this Review were similarly identified through searches of PubMed (from September, 2003, to December, 2008) for studies of statins with the search terms “pravastatin”, “lovastatin”, “atorvastatin”, “simvastatin”, “fluvastatin”, “cerivastatin”, “rosuvastatin”, “pitavastatin”, “HMG-CoA reductase inhibitor”, and “statin”. The search was restricted to trials in

High-risk patients

We identified statin trials that included 165 792 individuals at high risk of stroke (table).28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50 Incidence of all strokes was reduced by 18% (95% CI 13–23%, p<0·0001; figure 1), incidence of fatal stroke was reduced by 13% (−3 to 27, p=0·10; figure 2), although this did not reach statistical significance, and incidence of haemorrhagic stroke did not increase (RR 1·03, 95% CI 0·75–1·41, p=0·88; figure 3),

Intense reduction of LDL concentrations to target versus statin treatment

The latest recommendations for primary prevention of stroke from the European Stroke Organisation are that blood cholesterol should be checked regularly; high cholesterol (eg, LDL cholesterol >3·9 mmol/L [150 mg/dL]) should be managed with lifestyle modification (class IV, level C) and a statin (class I, level A). In secondary prevention of stroke, statin therapy is recommended for patients with non-cardioembolic stroke (class I, level A).59

These recommendations, which are based on expert

Conclusions

The relation between total and LDL cholesterol and stroke risk is inconsistent or weak. This inconsistency might be because of several reasons: many studies investigate total cholesterol, whereas different cholesterol components have different effects; studies typically look at total stroke, and different causes might be differently affected by cholesterol; and competing risk of death from other cardiovascular causes could further attenuate the relation between stroke (and fatal stroke in

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