STATINS IN STROKE

Abstract

Transient ischemic attack (TIA) and ischemic stroke are major healthcare problems. Stroke is the third cause of death in industrialized countries and the leading cause of disability. In general, increased total cholesterol levels are associated with higher rates of ischemic stroke, and low HDL levels have been shown to be a risk factor for ischemic stroke. International guidelines recommend lipid-lowering with either non-pharmacological or pharmacological interventions, in particular with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins). Statins are the treatment of choice for the management of hypercholesterolaemia because of their proven efficacy and safety profile. They also have an increasing role in managing cardiovascular risk in patients with relatively normal levels of plasma cholesterol. The potential positive effects of statins during an acute cerebrovascular ischemic event are two-fold: a neuroprotective effect, limiting damage and improving recovery from the presenting event (in particular for major stroke); and an antithrombotic and endothelial effect, preventing early recurrence.

Statins may prevent stroke by numerous mechanisms, including cholesterol lowering, increasing NO, and also anti-inflammatory and antithrombotic effects. Although all statins share a common mechanism of action, they differ in terms of their chemical structures, pharmacokinetic profiles, and lipid-modifying efficacy. The chemical structures of statins govern their water solubility, which in turn influences their absorption, distribution, metabolism and excretion. All statins are selective for effect in the liver, largely because of efficient first-pass uptake; passive diffusion through hepatocyte cell membranes is primarily responsible for hepatic uptake of lipophilic statins, while hydrophilic agents are taken up by active carrier mediated processes. Statin treatment is effective in primary and secondary stroke prevention and may also have neuroprotective effects in ischemic stroke therapy. Statins exert both peripheral and central effects which can be protective under diverse neuropathogenic conditions. In particular their ability to improve blood flow, to modulate the immune response and to reduce oxidative damage can lead to neuroprotection.

Some of the statin effects in reducing cardiovascular events can be ascribed to their ability to prevent thrombus formation by exerting modulatory effects on blood coagulation cascades, profibrinolytic mechanisms and platelet functions. Most guidelines now advocate the use of statins following an acute stroke; however, the choice of agent, timing of initiation, and dose and duration of treatment remain contentious. There was no effect on risk of hemorrhagic stroke. The benefit was seen in all ischemic stroke subtypes and not correlated with baseline cholesterol level. Discontinuation of statin therapy following acute cerebrovascular or cardiovascular events may impede vascular function and increase morbidity and mortality. Therefore, abrupt discontinuation of statin treatment in patients suffering ischemic stroke should be avoided.