HMG CoA reductase inhibitors (statins): use in stroke prevention and outcome after stroke

The use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) has been demonstrated to reduce the risk of primary and secondary ischemic stroke in patients with ischemic heart disease (relative risk reduction is 20-30%), confirmed by several prospective randomized placebo-controlled trials. At least one large prospective trial has also shown a similar benefit in patients without underlying ischemic heart disease. This is in contrast to an open-labeled trial conducted in the USA, which failed to demonstrate a significant benefit of statins in reducing stroke risk in hypertensive hyperlipidemic patients. It is less clear if treatment with statins before or after the onset of ischemic stroke also reduces its severity (improves outcome). Experimental animal studies where mice were pretreated with statins, demonstrated a reduced infarct size compared with untreated animals. Treatment with statins after stroke onset has also been demonstrated to enhance recovery without influencing infarct size (by increased angiogenesis, synaptogenesis and blood flow). A few clinical retrospective studies have demonstrated similar results. Prospective blinded placebo-controlled trials to test these findings are still lacking. This review discusses the various prospective trials in stroke prevention and available data on the effects of statins in improving outcome of established ischemic stroke. Alternate mechanisms of statins besides their lipid-lowering effect and relevance in reducing stroke risk and improving outcome are discussed. Finally, based on the present information, an evidence-based perspective about current and future use of statins in the short- and long-term management of ischemic stroke is presented.