Statins and ischemic stroke severity: cytoprotection

Cytoprotective or neuroprotective interventions would be of value if they could block the processes leading to delayed neuronal death or if they could delay the period between the onset of ischemia and irreversible necrotic injury, thereby lengthening the period for effective reperfusion therapy. Experimental studies in cell culture systems and laboratory animals show that statins have several potential cytoprotective actions, including promotion of angiogenesis, reduction of clot formation and facilitation of clot lysis, upregulation of endothelial nitric oxide synthase, downregulation of inducible nitric oxide synthase, reduction of excitotoxicity, and modulation of the inflammatory response. Clinically, statins appear to protect against vasospasm-related ischemic injury after subarachnoid hemorrhage. There have been no prospective randomized trials aimed at determining whether statins reduce acute stroke severity, and observational studies have had inconsistent results. Although a prospective, randomized trial assessing the effect of pre- or poststroke statin treatment on initial stroke severity would be the most appropriate study design to test for this type of effect, it is unlikely that such a trial will be conducted given the benefits of these drugs in reducing the risk of cardiovascular events and stroke in high-risk populations.