Statins for Stroke: Treating More Than Just Cholesterol
Statins for Stroke: Treating More Than Just Cholesterol
Abstract & Commentary
Soucre: Gertz K, et al. Withdrawal of statin treatment abrogates stroke protection in mice. Stroke. 2003;34:551-557.
HMG-CoA reductase inhibitors (statins) are known to reduce the risk of myocardial infarction and stroke. Statins are effective not only as cholesterol lowering agents but also have beneficial effects on endothelial cell function, as well as antithrombotic and anti-inflammatory effects. Through upregulation of endothelial nitric oxide synthase (eNOS) and the production of nitric oxide (NO), these agents augment regional blood flow and inhibit platelet aggregation. Because much of the damage from stroke likely occurs due to a failure of the microcirculation, augmentation of small vessel flow by NO may allow greater salvage of the ischemic penumbra and an attenuation of overall infarct size.
Gertz and associates studied mice treated with atorvastatin for 14 days prior to an experimental occlusion of the middle cerebral artery. These mice were compared with vehicle treated controls. Among treated mice, serum cholesterol measurements were not affected. In 2 additional experimental groups, atorvastatin was given for 14 days and then withdrawn either 2 days (14 ± 2d) or 4 days (14 ± 4d) prior to MCA occlusion. Treated animals had a 40% reduction in infarct volume compared to vehicle-treated animals. Beneficial effects of atorvastatin were blunted in the 14 ± 2d mice and stroke volumes were equal to control in the 14 ± 4d group. Measures of eNOS production (via PCR for eNOS mRNA) and platelet activation (measured as "tail bleeding times") showed deleterious rebound effects from statin withdrawal in the 14 ± 2d mice with return to baseline at 14 ± 4d. Thrombus formation induced by ligature of the inferior vena cava was significantly reduced by statin treatment. This protection was lost in the 14 ± 2 or 4d mice.
As Gertz et al observe, existing data in humans provide strong support for these results. In studies of patients with acute coronary syndromes, statins immediately following a myocardial infarction have a marked short-term protective effect on both cardiac recurrent events and stroke. In the MIRACL trial,1 there was a 50% reduction in stroke rates over the first 16 weeks after MI among patients on atorvastatin. This effect was independent of any cholesterol lowering.
Commentary
Statins have a crucial role in the secondary prevention of stroke and should be started immediately in the hospital upon the diagnosis of cerebral infarction. Statins furthermore should be prescribed and maintained for any patient at high risk for stroke, such as those with prior TIA or known carotid artery disease. An aggressive LDL cholesterol goal of < 100 should be the target for statin therapy, and consideration for a statin should be made even for patients with lipids in this optimal range. — Alan Z. Segal
Dr. Segal is Assistant Professor, Department of Neurology, Weill-Cornell Medical College, Attending Neurologist, New York Presbyterian Hospital.
Reference
1. Schwartz GG, et al. JAMA. 2001;285:1711-1718.
HMG-CoA reductase inhibitors (statins) are known to reduce the risk of myocardial infarction and stroke. Statins are effective not only as cholesterol lowering agents but also have beneficial effects on endothelial cell function, as well as antithrombotic and anti-inflammatory effects.Subscribe Now for Access
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