THE USE OF HIGH-DOSE STATIN THERAPY IN ISCHEMIC STROKE PATIENTS. High-Dose Statins Should Be Used in All Acute Ischemic Strokes

This case raises several questions: (1) Is the role for statins in acute ischemic stroke to improve outcome, to reduce the chances of a recurrent stroke, or both? (2) Do the benefits associated with high dose statin use extend across all stroke sub-types including catheter related stroke? Irrespective of the etiology of ischemic stroke, use of statins has been associated with reduced infarct size and a more favorable outcome.1 This is reinforced by our own observations that statins given within 4 weeks of stroke onset improve stroke outcome at 90 days compared with subjects not given statins. The benefits were more pronounced in statin-naïve patients who received statins early on after the stroke as compared with patients on statins before stroke onset. Furthermore, the benefits extended across all stroke types including cardioembolic stroke.2,3 Similarly, using the Kaiser Permanente database of 12 000 patients, investigators found a strong direct correlation of prestroke and post stroke statin use and stoke outcome. Hyperlipidemia was not a predictor of outcome and the authors found the small lipid-lowering effect to be out of proportion to the significantly improved acute ischemic stroke outcomes, stressing the importance of the pleiotropic effects of statins. The study also found better outcomes with high-dose ( 60 mg) versus low-dose ( 60 mg) statins and the benefits extended to all acute ischemic stroke subtypes.4 The Dublin study, the largest to date, addressed 3 important questions: does preor poststroke statins use improve clinical outcome at discharge, are there predictors of such improvement and whether low-dose atorvastatin achieved the same results as high-dose. A benefit of statins given prestroke as well as after stroke onset was seen with a greater magnitude effect with poststroke statins. Their study also reconfirmed that higher doses of statins were associated with better outcomes (atorvastatin at 40 mg being better than 20 mg, which in turn was better than 10 mg). Interestingly enough, even 10 mg did show a benefit but not of the same magnitude as the higher doses.5 This is not surprising given the growing realization that although being risk factors for ischemic stroke, neither total cholesterol or low-density lipoprotein cholesterol is associated with outcome of acute ischemic stroke and that the many pleiotropic effects of statins are perhaps more important at least in the first 3 to 7 days after stroke. Among the most relevant pleiotropic effects are dose-dependent elevation of endothelial nitric oxide synthetase, which in turn regulates the endothelial tone and laminar flow. Statins also enhance endogenous tissue-type plasminogen activator, exert an antithrombotic effect, improve collateral blood flow, and reduce inflammatory mediators. Collectively, these dose-dependent effects of statins improve blood flow to the penumbra and help with autolysis of clots, reduce the chances of reocclusion, reduce the infarct size, and improve clinical outcome.4,6 Are we causing harm by exposing patients to high-dose statins? All the evidence from randomized trials and observation studies point to the contrary. Two large prospective randomized studies, the Heart Protection Study (simvastatin