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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Statin medications initiated during percutaneous coronary intervention have been evaluated in clinical trials mainly to assess if this therapy reduces subsequent restenosis. The benefit of statin therapy on individual cardiovascular outcomes other than restenosis is largely unknown. Hence, a meta-analysis of the available randomized trials was conducted to evaluate individual cardiovascular outcomes with statin therapy compared with placebo after elective percutaneous coronary intervention. In all, there were 6 studies available for analysis (Prevention of Restenosis by Elisor After Transluminal Coronary Angioplasty [PREDICT], Fluvastatin Angioplasty Restenosis [FLARE], the Lescol Intervention Prevention Study [LIPS], German Atorvastatin Intravascular Ultrasound [GAIN], Atorvastatin for Reduction of Myocardial Damage During Angioplasty [ARMYDA], and a study by Briguori et al) that randomized 3,941 patients (1,967 to statins and 1,974 to placebos). Clinical follow-up ranged from 1 day to 45 months. The incidence of myocardial infarction was 3.0% in the statin group and 5.2% in the placebo group (odds ratio [OR] 0.57, 95% confidence interval [CI] 0.42 to 0.78, p<0.0001). The incidence of all-cause mortality was 2.3% versus 3.0% (OR 0.74, 95% CI 0.50 to 1.1, p=0.14), that of cardiovascular mortality was 0.71% versus 1.2% (OR 0.58, 95% CI 0.30 to 1.11, p=0.10), and that of repeat surgical or percutaneous revascularization was 19.6% versus 21.9% (OR 0.89, 95% CI 0.78 to 1.02, p=0.098) in the statin arm versus the placebo arm, respectively. The incidence of stroke was 0.4% in the statin arm and 0.08% in the placebo arm (OR 3.00, 95% CI 0.60 to 14.77, p=0.18). In conclusion, statin therapy initiated at the time of elective percutaneous coronary intervention significantly reduces myocardial infarction.
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PMID:Meta-analysis of the role of statin therapy in reducing myocardial infarction following elective percutaneous coronary intervention. 1782 70

Several large-scale clinical trials have assessed the efficacy of atorvastatin in the primary and secondary prevention of cardiovascular events in patients with diabetes mellitus and/or metabolic syndrome. In primary prevention, CARDS (Collaborative Atorvastatin Diabetes Study) showed that atorvastatin 10 mg/day (vs placebo) reduced relative risk of the composite primary endpoint (acute coronary heart disease [CHD] events, coronary revascularisation, or stroke) by 37% (p = 0.001). This decrease was similar to decreases in major cardiovascular events in the ASCOT-LLA (Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm) trial and HPS (Heart Protection Study). However, in CARDS, atorvastatin efficacy was evident as early as 6 months after starting treatment, whereas in HPS, simvastatin efficacy was noticeable only from about 15-18 months after starting treatment. In the ASCOT-LLA trial, in 2226 hypertensive diabetic patients without previous cardiovascular disease, atorvastatin (vs placebo) reduced the relative risk of all cardiovascular events and procedures by 25% (p = 0.038). In secondary prevention, substudies of the GREACE (GREek Atorvastatin and Coronary-heart-disease Evaluation), TNT (Treating to New Targets) and PROVE-IT (PRavastatin Or atorVastatin Evaluation and Infection Therapy) trials reported results for the approximately 15-25% of study participants who had diabetes. In the GREACE substudy, atorvastatin (vs physicians' standard care) significantly reduced the relative risk of total mortality by 52% (p = 0.049), coronary mortality by 62% (p = 0.042), coronary morbidity by 59% (p < 0.002) and stroke by 68% (p = 0.046). In the TNT substudy, incidence of the primary endpoint was significantly lower in diabetic patients treated with atorvastatin 80 mg/day rather than 10 mg/day (13.8% vs 17.9%; relative risk 0.75; p = 0.026). In the PROVE-IT substudy, a significantly lower incidence of acute cardiac events was reported for atorvastatin versus pravastatin recipients (21.1% vs 26.6%; p = 0.03) and, therefore, an absolute risk reduction of 5.5% was associated with atorvastatin therapy. ASPEN (Atorvastatin Study for Prevention of coronary heart disease Endpoints in Non-insulin-dependent diabetes mellitus) - a mixed primary and secondary prevention trial in diabetic patients - found that a 29% lower low-density lipoprotein-cholesterol level was seen with atorvastatin than placebo at endpoint (p < 0.0001); however, the reduction in composite primary endpoint of major cardiovascular events (cardiovascular mortality, nonfatal major cardiovascular event or stroke, and unstable angina requiring hospitalisation) with atorvastatin (13.7% vs 15.0% with placebo), and reduction in acute myocardial infarction relative risk of 27% with atorvastatin were not statistically significant. In CHD patients with metabolic syndrome (n = 5584) in a sub-analysis of the TNT trial, intensive versus lower-dosage atorvastatin therapy reduced the relative risk of major cardiovascular and cerebrovascular events by 29% (p < 0.0001). The analysis also revealed that CHD patients with, rather than those without, metabolic syndrome had a 44% greater level of absolute cardiovascular risk, thus clearly underscoring the clinical feasibility of administering intensive lipid-lowering therapy to CHD patients with metabolic syndrome. In summary, several patient populations, from definitive, large-scale studies, are now available to corroborate the integral place of atorvastatin--in line with various regional and internationally accepted disease management guidelines--in the primary and secondary prevention of cardiovascular events in patients with diabetes and/or metabolic syndrome.
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PMID:Atorvastatin efficacy in the prevention of cardiovascular events in patients with diabetes mellitus and/or metabolic syndrome. 1791 May 20

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.
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PMID:Atorvastatin: its clinical role in cerebrovascular prevention. 1791 May 21

Atherosclerosis, especially when manifested as coronary artery disease (CAD), continues to be the number one cause of mortality and morbidity in developed nations and will soon become so in developing countries. Survivors of an acute heart attack have an increased risk of illness and death that is 1.5-15 times greater than in the general population. Sudden death occurs in myocardial infarction (MI) survivors at a rate 4-6 times greater than in the general population. After an initial recognized MI, 25% of male and 38% of female survivors die within 1 year. Within 6 years after a recognized MI, 18% of men and 35% of women will have a second MI, 7% of men and 6% of women will suffer sudden death, and 22% of men and 46% of women will be disabled with heart failure. Aggressive secondary prevention, therefore, is the key to containing and reversing the "malignant" natural history of CAD, since patients with CAD or CAD risk equivalents are already in the "high risk" category according to the Adult Treatment Panel III (ATP III) of the National Cholesterol Education rogram (NCEP). Treatment of dyslipidemia, especially the reduction of low-density lipoprotein (LDL) cholesterol levels to below 100 mg/dl, was recommended by the 2001 NCEP-ATP Guidelines. In 2004, based on the increasing evidence from several major clinical trials between 2001 and 2004, the NCEP-ATP reaffirmed its LDL goal of < 100 mg/dl in patients with CAD or coronary disease risk equivalents (including multiple risk factors), with an optional LDL goal of < 70 mg/dl in very-high-risk patients (including patients with established coronary heart disease plus other highrisk conditions) Findings from major studies, such as the Treating to New Targets (TNT) study, the Scandinavian Simvastatin Survival Study (4S), the Collaborative Atorvastatin Diabetes Study (CARDS), the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial and, more recently, the Lipid-Lowering Arm of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT-LAA), lend support to the idea that greater LDL cholesterol lowering than that achieved with standard doses of statins may be warranted in patients with CAD and metabolic syndrome, CAD and diabetes, CAD and congestive heart failure, and CAD and renal insufficiency. On the other hand, additional lipid reduction may also be warranted in patients with risk factors such as diabetes, hypertension or a history of stroke, but without manifest CAD and despite relatively normal cholesterol levels. These newer indications for statins, atorvastatin in particular, as part of more aggressive secondary and primary prevention, are reviewed in this paper.
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PMID:Expanding roles for atorvastatin. 1859 99

Elderly individuals are at increased risk of coronary heart disease (CHD) and account for a majority of CHD deaths. Several clinical trials have assessed the beneficial effects of statins in individuals with, or at risk of developing, CHD. These trials provide evidence that statins reduce risk and improve clinical outcomes even in older patients; however, statin therapy remains under-utilized among the aged. Atorvastatin has been widely investigated among the older subjects and has the greatest magnitude of favorable effects on clinical outcomes of CHD. The pharmacokinetic properties of atorvastatin allow it to be used every other day, a factor which may decrease adverse events and be especially important in the elderly. The purpose of this article is to review the evidence available from randomized clinical trials regarding the safety and efficacy of atorvastatin in primary and secondary prevention of CHD and stroke in older patients and to discuss issues such as drug interactions, patient compliance and cost-effectiveness, which affect prescription of lipid-lowering therapy among older patients.
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PMID:Atorvastatin and cardiovascular risk in the elderly--patient considerations. 1868 52

Statins have multiple effects, including anti-inflammatory actions, lowering C-reactive protein levels, and reducing coronary events. We performed a post hoc analysis of the randomized placebo-controlled 4D Study that had evaluated the efficacy and safety of atorvastatin in 1255 patients with type 2 diabetes mellitus who were on maintenance hemodialysis. Here we determined the relationship between atorvastatin treatment, C-reactive protein, and the outcome of patients who had pre-specified and adjudicated endpoints of all-cause mortality, composite vascular endpoint, myocardial infarction, sudden death, and stroke. Atorvastatin had no significant effect on the risk of composite vascular endpoint or death relative to placebo in any quartile of baseline C-reactive protein. These baseline levels were not significantly different between the treated and placebo group and remained stable at 6 months on atorvastatin but significantly increased in those patients on placebo. All of the patients with baseline C-reactive protein in the fourth quartile had a significantly increased risk of deaths and in composite vascular endpoint compared to patients in the first quartile. The mean value of two consecutive C-reactive protein measurements was associated with significant increases in the risk of sudden death, stroke, all-cause mortality and composite vascular endpoint. Our results show that C-reactive protein was highly predictive of outcome, but atorvastatin treatment was not associated with reduced relative risks in the composite vascular endpoint or mortality in patients on hemodialysis with or without inflammation.
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PMID:Effect of atorvastatin on inflammation and outcome in patients with type 2 diabetes mellitus on hemodialysis. 1881 79

Ischemic stroke is a leading cause of death in the United States, and diabetes mellitus is a major risk factor for stroke. Our previous work showed that type II diabetic rats [Goto-Kakizaki (GK)] have more bleeding after stroke than their normoglycemic controls (Wistar). Our aim was to evaluate the vascular protective properties of acute atorvastatin therapy after experimental ischemic stroke in diabetes and to explore the effect of stroke in GK rats compared with their normoglycemic controls. Fifty male Wistar and 40 GK rats (270-305 g) underwent 3 h of middle cerebral artery occlusion followed by reperfusion for 21 h. Animals received atorvastatin (5 mg/kg), atorvastatin (15 mg/kg), or vehicle, administered by oral gavage, one dose 5 min after reperfusion and a second dose after 12 h. At 24 h, functional outcome was measured, and brain tissue was analyzed for infarct volume, hemoglobin content, and molecular biomarkers. Plasma was collected for analysis of atorvastatin concentrations. Atorvastatin-treated groups had significantly lower bleeding rates (p = 0.0011) and infarct volume (p = 0.0007) compared with controls. There was a significant reduction in hemoglobin content and infarct volume only in the higher dose group (15 mg/kg) (p < 0.05), and these benefits were more than 4 times greater in the diabetic animals. Atorvastatin (15 mg/kg) improved neurological outcome in both Wistar and GK rats (p = 0.029) at a peak concentration of 27 to 77 ng/ml and was associated with an increase in Akt phosphorylation (p = 0.0007). We concluded that atorvastatin is a vascular protective agent after experimental ischemic stroke, especially in diabetes.
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PMID:Early atorvastatin reduces hemorrhage after acute cerebral ischemia in diabetic rats. 1947 37

The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) study is a prospective, randomized, placebo-controlled trial that was designed to determine whether 80 mg/d of atorvastatin reduced the risk of fatal or nonfatal stroke in patients who had previously experienced a stroke or transient ischemic attack. It is unique in that it is the only trial to study this cohort of patients with no known coronary heart disease. The review recaps the results of the primary SPARCL data and discusses the findings of subsequent analyses that extend the conclusions from the study. Atorvastatin reduced the risk of stroke to a clinically persuasive degree. This benefit was present despite a small increase in risk of intracerebral hemorrhage. Factors were identified in SPARCL that might reduce this risk if implemented. Further subanalyses addressed other questions relative to stroke profile of benefit and potential mechanisms of statin action. SPARCL has established that statins have an important role in secondary stroke prevention.
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PMID:Review of the SPARCL trial and its subanalyses. 1950 Apr 96

We investigated the neuroprotective effect of atorvastatin in combination with delayed thrombolytic therapy in a rat model of embolic stroke. Rats subjected to embolic middle cerebral artery (MCA) occlusion were treated with atorvastatin at 4 h, followed by tissue plasminogen activator (tPA) at 6 or 8 h after stroke. The combination of atorvastatin at 4 h and tPA at 6 h significantly decreased the size of the embolus at the origin of the MCA, improved microvascular patency, and reduced infarct volume, but did not increase the incidence of hemorrhagic transformation compared with vehicle-treated control animals. However, monotherapy with tPA at 6 h increased the incidence of hemorrhagic transformation and failed to reduce infarct volume compared with the control group. In addition, adjuvant treatment with atorvastatin at 4 h and with tPA at 6 h reduced tPA-induced upregulation of protease-activated receptor-1, intercellular adhesion molecule-1, and matrix metalloproteinase-9, and concomitantly reduced cerebral microvascular platelet, neutrophil, and fibrin deposition compared with rats treated with tPA alone at 6 h. In conclusion, a combination of atorvastatin and tPA extended the therapeutic window for stroke to 6 h without increasing the incidence of hemorrhagic transformation. Atorvastatin blocked delayed tPA-potentiated adverse cerebral vascular events, which likely contributes to the neuroprotective effect of the combination therapy.
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PMID:Atorvastatin extends the therapeutic window for tPA to 6 h after the onset of embolic stroke in rats. 1963 98

Statins are the mainstay of therapy in coronary artery disease and hypercholesterolemia. Atorvastatin is a 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitor that is taken once daily. It has been shown to considerably reduce cardiovascular mortality events. Recently, several trials have demonstrated that atorvastatin has pleiotropic effects beyond its lipid-lowering capacities. Atorvastatin is especially beneficial in diabetics for stroke prevention and improving cardiovascular mortality risk.
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PMID:Atorvastatin: beyond lipid-lowering effects in the diabetic population. 1980 88


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