cerivastatin and Stroke

In this overview the actual guideline-recommendations for anticoagulation in atrial fibrillation and the problems of the currently available therapy are discussed. Furthermore an outlook over future developments in this field is given. Effective anticoagulation can prohibit thrombembolic events and is thus essential for the prognosis of patients suffering from atrial fibrillation. Until now vitamin-K-antagonists (VKAs) and acetylsalicylic acid (ASA) are available for oral anticoagulation in these patients. VKAs demonstrate a satisfying efficiency combined with rather high bleeding hazard. ASA on the other hand allows only moderate risk reduction with minimal side effects. Thus the guidelines recommend anticoagulation tailored to the individual risk, which can be evaluated by the CHADS2-Score. New therapeutic strategies, like the factor Xa inhibitor rivaroxaban or the factor II inhibitor dabigatran, are actually evaluated in phase III studies. These drugs bear the hope of higher efficiency combined with improved safety and much more comfortable use in the daily practice (e. g. no need for INR measurement, no dose adaptation).

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Benzimidazoles; Blood Coagulation; Blood Coagulation Factors; Dabigatran; Female; Humans; Middle Aged; Pyridines; Risk Factors; Stroke; Vitamin K

Topics: Anti-Inflammatory Agents, Non-Steroidal; Clinical Trials as Topic; Cyclooxygenase 2 Inhibitors; Drug and Narcotic Control; Drug Approval; Health Policy; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lactones; Myocardial Infarction; Probability; Product Surveillance, Postmarketing; Pyridines; Research Design; Rhabdomyolysis; Risk Assessment; Stroke; Sulfones; Treatment Outcome; United States; United States Food and Drug Administration

Recent clinical studies suggest that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) exert protective effects against nonhemorrhagic stroke. In a murine cerebral ischemia model produced by occlusion of the middle cerebral artery, statins were shown to reduce infarct size. However, the effect of statins on hypertension-based stroke is unknown. The purpose of this study is to clarify the effect of a statin on stroke in stroke-prone spontaneously hypertensive rats (SHR-SP), in which both cerebral hemorrhage and infarction occur.. We treated SHR-SP chronically from 4 weeks of age with cerivastatin (2 mg/kg per day by gavage) or vehicle. The physiological parameters, the incidence of stroke-associated symptoms, and mortality were assessed.. At 14 weeks of age, the incidence (13+/-3% versus 37+/-8%; P<0.01) and the size of stroke (1.6+/-0.2 versus 2.2+/-0.1 arbitrary units; P<0.01) were significantly decreased by cerivastatin, although blood pressure and plasma cholesterol levels were not different. Moreover, stroke-associated symptoms and early mortality of SHR-SP were markedly reduced in the statin-treated group (mortality at the age of 15 weeks: 15% versus 50%; P<0.05). Statin treatment significantly reduced superoxide production from nonstroke parenchyma of brain and infiltration of inflammatory cells to the stroke lesions.. Our data show that a high dose of statin exerts protection against hypertension-based stroke and ameliorates the disease severity via inhibition of superoxide production and modulation of inflammation in brain.

Topics: Animals; Blood Pressure; Blood Vessels; Brain; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Inflammation; Kinetics; Lipids; Male; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Pyridines; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Stroke; Superoxides; Survival Analysis