The role of statins in the prevention of stroke

Previous randomized trials have shown that statins may reduce the risk of stroke in high-risk patients. There were no evidences however that statins can reduce recurrent strokes. In the SPARCL trial, compared to placebo, the patients with a recent stroke or TIA randomized to atorvastatin 80 mg per day had a significant 16% relative risk reduction of stroke, and a 35% reduction in major coronary events. This was obtained despite 25% of patients allocated to placebo arm were prescribed a commercially available statin outside the trial. A post-hoc analysis used blinded LDL-C measurements (taken at study visits during the trial) as a marker of adherence to lipid lowering therapy. Compared to the group with no change or an increase in LDL-C (the group adherent to placebo or not taking a statin), the group with >50% reduction in LDL-C had a significant 31% reduction in stroke. The meta-analysis of trials that evaluated intensive LDL-C lowering (n=29,906 patients) shows that, compared to standard statin therapy, intense therapy reduced the risk of stroke by 17% (95% CI, 4 to 28%; p=0.01) with no heterogeneity between trials, and the risk of major cardiovascular events (stroke, myocardial infarction and vascular death) by 20% (95% CI, 14 to 26%; p<0.0001) with no heterogeneity between trials. Next step is to define whether achieving a LDL-C less than 70 mg/dL is better than a standard dose of statin (LDL around 100-110 mg/dL) in the secondary prevention of stroke. Other directions include evaluation of combination therapy (statin and ezetimide, statin and HDL-raising drugs), primary prevention of stroke and TIA as well as other cardiovascular events in patients at intermediate risk, and to evaluate the benefit/risk of PPAR agonist such as fibrate, alone or in combination with statins. Statins are effective in reducing both first-ever and recurrent stroke in high-risk patients, and this effect seems driven by the extent of LDL-C lowering.