Paris, France - Reducing LDL-cholesterol levels with statins is effective in reducing initial and recurrent stroke, according to an updated meta-analysis [1]. Data from 24 randomized clinical trials showed that lipid lowering with statins cut the risk of stroke by one-fifth compared with controls, report investigators.

The meta-analysis, published in the May 2009 issue of Lancet Neurology, includes more than 165 000 patients and shows that for every 39-mg/dL decrease in LDL-cholesterol levels, there was a 21% reduction in the relative risk of stroke.

The researchers, Drs Pierre Amarenco and Julien Labreuche (Paris-Diderot University, France), who also include a review of the field in their paper, point out that the relationship between total and LDL cholesterol and stroke risk is inconsistent or weak. Despite this, statin therapy is an important treatment in stroke prevention, with studies showing that lowering cholesterol levels with statins reduces the risk of stroke in high-risk populations and patients with noncardioembolic stroke or transient ischemic attack (TIA).

"The most important challenges for clinicians will be to implement evidence-based therapy and expert opinion recommendations in clinical practice," write Amarenco and Labreuche. They note that just 35% of patients in one recent European survey were treated to target after a vascular event.

In their review, the authors point to some of the inconsistencies in the literature regarding cholesterol and stroke risk. One recent meta-analysis of 61 prospective observational studies, reported by heartwire, failed to find any association of total cholesterol (TC) with stroke mortality. Other studies have suggested it is important to account for stroke types, however, with previous trials showing reductions in ischemic stroke with lower serum cholesterol concentrations.

In this most recent meta-analysis, the authors included 24 studies, among them the recent SEARCH and JUPITER trials, as well as SPARCL, TNT, IDEAL, PROVE-IT, and the Heart Protection Study (HPS). The majority of studies included were for the primary prevention of stroke, while SPARCL was a secondary-prevention trial, and HPS, LIPID, and CARE included patients with prior cardiovascular disease.

Overall, the incidence of all strokes was reduced 18%, and there was also a statistically nonsignificant 13% reduction in the risk of fatal stroke. In secondary prevention, reducing LDL-cholesterol levels with statins significantly reduced the risk of recurrent stroke and major cardiovascular events. Overall, the incidence of hemorrhagic stroke did not increase, which is in contrast to SPARCL and HPS, two studies that suggested an increased risk of hemorrhagic stroke in secondary prevention.

"Because of increased risk incidence of hemorrhagic stroke seen in HPS and SPARCL, we recommend caution when considering statin therapy in patients with prior cerebral hemorrhage," write Amarenco and Labreuche. "Pending further data from other secondary-prevention trials in patients with stroke, we would only prescribe statins to patients who are at high risk of major coronary or other atherothrombotic events and would not aim to aggressively reduce cholesterol concentrations."

They suggest future areas of study involve testing intensive lipid-lowering strategies for stroke prevention, similar to the host of lower-is-better cholesterol trials in the past few years. Other drugs that raise HDL-cholesterol levels should also be tested, as epidemiological evidence suggests raising HDL cholesterol reduces the risk of stroke, while other studies have shown the LDL:HDL cholesterol ratio to be the best predictor of stroke and MI. Triglyceride-lowering therapies also need to be tested in randomized, controlled trials, they add.