Pierre Amarenco, Philippa C. Lavallée, Mikael Mazighi, Julien Labreuche.

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.