J Neurol Stroke 2014, 1(3): 00014 Submit Manuscript | http://medcraveonline.com Journal of Neurology & Stroke The Current Status of Statins in Stroke Prevention Editorial Volume 1 Issue 3 - 2014 Aashrai SV Gudlavalleti 1 and Majaz Moonis 2 * 1 Department of Neurology, University of Massachusetts Medical School, USA 2 Department of Neurology, University of Massachusetts Medical School, USA *Corresponding author: Majaz Moonis. Department of Neurology, University of Massachusetts Medical School, University Campus, 55 lake Avenue North , Worcester, Massachusetts, 01655, USA, Tel: 508-334-2527; Fax: 508-856-6778; Email: Majaz. Moonis@umassmemorial.org Received: July 12, 2014 | Published: July 14, 2014 Abbreviations eNOS : endothelial Nitric Oxide Synthase; CARE: Cholesterol and Recurrent Events study; LIPID: Long-Term Intervention with Pravastatin in Ischemic Disease; JUPITER: Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin; s-CRP: sensitive C Reactive Protein; SPARCL: Stroke Prevention by Aggressive Reduction in Cholesterol Levels; J-STARS: Japan Statin Treatment Against Recurrent Stroke; RAPID-TIA: Rapid Primary care Initiation of Drug treatment for Transient Ischaemic Attack; AIS: Acute Ischemic Stroke; ThraST: THRombolysis and Statins Introduction Statins or 3-hydroxl- 3-methyl glutaryl coenzyme A reductase inhibitors are drugs that are primarily used to treat dyslipidemia [1]. They are beneficial in primary and secondary prevention of stroke [2]. Statins are recommended for use in ischemic stroke related to small and large vessel disease, although studies suggest that their use in primary prevention and in other subtypes of stroke may also be beneficial [1,3,4]. The benefits of statins are related to their pleiotropic effects and to their lipid lowering properties. However, the predominant effect in hyperacute stroke is probably pleotropic rather than lipid lowering [1,2]. Blanco et al. [5] found that withdrawal of statins in hyperacute stroke, even for 72 hours was related with a significantly worse outcome. This effect was independent of the LDL-C levels. The major pleiotropic effect of statins is the expression of endothelial Nitric Oxide Synthase (eNOS) which causes vasodilation and enhancement of cerebral blood flow. This, in addition to enhancement of collateral circulation and cerebrovascular reactivity, helps improve the infarct volume [6,7]. Other pleiotropic effects include angiogenesis, anti -inflammatory action, stabilization of the endothelial layer and enhancement of tissue plasminogen activator [1,2]; all of which can contribute to improvement of cerebral blood flow and to the reduction of the infarct volume. Beneits of Statin use in Stroke Prevention Prevention of first ever strokes and recurrent strokes A summary of the major randomized controlled trials and meta-analyses studying the role of statins in prevention of stroke has been provided in Table 1. The CARE (Cholesterol and Recurrent Events study) [8] and the LIPID (Long-Term Intervention with Pravastatin in Ischemic Disease) [9] trials recruited patients with MI, and with MI and unstable angina, respectively. In the former study, the investigators found a risk reduction of 32% (95% CI: 4-52 %; p=0.03) in all cause stroke in the statin group. In the latter study, there was a 23% risk reduction (95% CI: 5-38%, p=0.02) in ischemic stroke in the statin group. In the Heart Protection Study [10] 20,536 adults aged between 40-80 years who were suffering from diabetes, coronary heart disease or other occlusive arterial disease were randomized to receive either simvastatin or placebo. There was significant reduction in the incidence of fatal and non- fatal stroke (4.3% vs. 5.7%, p<0.001). Overall, the treatment group had a highly significant reduction in the incidence of first stroke, which was attributed to the reduction in ischemic strokes (2.8% vs. 4%, p<0.001), since there was no difference found in the incidence of hemorrhagic strokes (0.5% vs 0.5%, p=0.8). A systematic review of eighteen randomized controlled trials [11] encompassing 114,081 subjects, showed that statins reduced the overall incidence of stroke as compared to placebo (odds ratio: 0.80; 95% CI: 0.74-0.87; p<0.00001) in high risk individuals. The benefits of statins on major cardiovascular events in the elderly were confirmed by a meta-analysis [3] including eight randomized controlled trials which encompassed 24,674 subjects. The study found that compared to placebo, statins significantly reduced the Abstract Statins or 3-hydroxl- 3-methyl glutaryl coenzyme A reductase inhibitors are drugs that are primarily used to treat dyslipidemia. Statins are recommended for use in ischemic stroke related to small and large vessel disease, although studies suggest that their use in primary prevention and in other subtypes of stroke may also be beneficial. The benefits of statins in stroke prevention and improvement of neurologic outcome after acute ischemic stroke are related to their pleiotropic effects. These include expression of endothelial Nitric Oxide Synthase (eNOS), angiogenesis, anti -inflammatory action, stabilization of the endothelial layer and enhancement of tissue plasminogen activator. Numerous randomized controlled trials, meta-analyses and population based studies have highlighted the importance of statins in prevention of stroke and improvement of neurologic outcome. Many concerns have been raised regarding their adverse effects such as myopathy, elevated transaminases and increased risk of intracranial hemorrhage and cancer. However, studies have shown that statins can be used over a long period of time without any significant adverse events. Current stroke prevention guidelines recommend the initiation of statins in patients with evidence of atherosclerosis and an LDL cholesterol level >100mg/dL without known coronary heart disease, and also in patients with elevated cholesterol or comorbid coronary heart disease.