Atorvastatin: its clinical role in cerebrovascular prevention

Abstract

An association between hypercholesterolaemia and ischaemic stroke has not yet been clearly defined by observational studies. In clinical trials, however, cholesterol-lowering treatments appear to consistently reduce stroke risk. Data are now available from various primary prevention studies - ALLHAT-LLT (Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack, Lipid-Lowering Therapy), ASCOT-LLA (Anglo-Scandinavian Cardiac Outcomes Trial, Lipid-Lowering Arm), CARDS (Collaborative Atorvastatin Diabetes Study, WOSCOPS (West of Scotland COronary Prevention Study) - and secondary prevention studies - 4S (Scandinavian Simvastatin Survival Study), CARE (Cholesterol and Recurrent Events), GREACE (GREek Atorvastatin and Coronary-heart-disease Evaluation), HPS (Heart Protection Study), LIPID (Long-term Intervention with Pravastatin in Ischaemic Disease), MIRACL (Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering), SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels), TNT (Treating to New Targets) - confirming the ability of statins to reduce stroke risk. Regarding primary prevention, post hoc analyses showed pravastatin reduced the relative risk of stroke by 9-11% (not statistically significant) in the ALLHAT-LLT and WOSCOPS trials, whereas atorvastatin reduced this risk by 27-48% in the ASCOT-LLA (p = 0.024) and CARDS trials. It remains to be established in prospective studies whether cholesterol-lowering is effective in the primary prevention of stroke. Regarding secondary prevention, in five placebo-controlled studies (4S, CARE, HPS, LIPID, MIRACL) involving a total of >40 000 patients with coronary heart disease (CHD), statin therapy reduced the relative risk of fatal or nonfatal stroke by 19-50% (p < or = 0.048); the largest decrease was produced by atorvastatin in the MIRACL study (-50%, p = 0.045). In addition, high-dosage atorvastatin reduced stroke risk by 25% (p = 0.02) relative to lower-dosage therapy in the TNT trial, and by 47% (p = 0.034) relative to 'usual' care in the GREACE study. A post hoc analysis of data for 3280 HPS study participants who had had a previous stroke revealed that simvastatin reduced major vascular events by 20% (p = 0.001).The SPARCL study assessed the secondary preventive efficacy of atorvastatin versus placebo in 4731 patients with a history of stroke or transient ischaemic attack (TIA), but without CHD. Atorvastatin reduced the adjusted relative risk of fatal or nonfatal stroke by 16% (p = 0.03), and that of fatal stroke alone by 43% (p = 0.03). Among secondary study endpoints, atorvastatin reduced the relative risks of stroke and TIA (-23%; p < 0.001), TIA alone (-26%; p = 0.004), and ischaemic stroke (-22%; p = 0.01). Overall, SPARCL study findings suggest that intensive atorvastatin therapy should be started immediately after a stroke or TIA. In summary, atorvastatin has developed a well defined role in the primary and secondary prevention of cerebrovascular disease, and appears to have a particularly prominent place in preventing such disease in CHD patients, and in the post-stroke and post-TIA setting in patients without CHD.