Background and Purpose-Although experimental data suggest that statin therapy may improve neurological outcome after acute cerebral ischemia, the results from clinical studies are conflicting. We performed a systematic review and meta-analysis investigating the relationship between statin therapy and outcome after ischemic stroke. Methods-The primary analysis investigated statin therapy at stroke onset (prestroke statin use) and good functional outcome (modified Rankin score 0 to 2) and death. Secondary analyses included the following: (1) acute poststroke statin therapy (≤72 hours after stroke), and (2) thrombolysis-treated patients. Results-The primary analysis included 113 148 subjects (27 studies). Among observational studies, statin treatment at stroke onset was associated with good functional outcome at 90 days (pooled odds ratio [OR], 1.41; 95% confidence interval [CI], 1.29-1.56; P<0.001), but not 1 year (OR, 1.12; 95% CI, 0.9-1.4; P=0.31), and with reduced fatality at 90 days (pooled OR, 0.71; 95% CI, 0.62-0.82; P<0.001) and 1 year (OR, 0.80; 95% CI, P=0.01). In the single randomized controlled trial reporting 90-day functional outcome, statin treatment was associated with good outcome (OR, 1.5; 95% CI, 1.0-2.24; P=0.05). No reduction in fatality was observed on meta-analysis of data from 3 randomized controlled trials (P=0.9). In studies restricted to of thrombolysis-treated patients, an association between statins and increased fatality at 90 days was observed (pooled OR, 1.25; 95% CI, 1.02-1.52; P=0.03, 3 studies, 4339 patients). However, this association was no longer present after adjusting for age and stroke severity in the largest study (adjusted OR, 1.14; 95% CI, 0.90-1.44; 4012 patients). Conclusion-In the largest meta-analysis to date, statin therapy at stroke onset was associated with improved outcome, a finding not observed in studies restricted to thrombolysis-treated patients. 5-12 Experimental and clinical data also provide some evidence that statins may have neuroprotective effects after acute cerebral ischemia. [7][8][9][10][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] In animal models, treatment with statins either before, or early after, cerebral arterial occlusion has been associated with reduced infarct volume and improved neurological function. [5][6][7][8][9][10]13,14 Data are conflicting regarding the relationship between acute statin therapy and outcome after human ischemic stroke. Some authors have reported improved survival and functional outcome associated with statin treatment, but these findings have not been consistently replicated. [15][16][17][18][19][20][21][22][23][24][25][26][27][28][31][32][33][34][35][36] Interpretations can be difficult because of limited sample sizes in some reports and possible bias in statin allocation in other studies, particularly those in which statins were allocated in a nonrandomized fashion. Some authors have also reported worse outcomes in patients treated with the combination of acute statins and intravenous thro...

Background and Purpose-Statins improve infarct volume and neurological outcome in animal stroke models. We investigated the relationship between statin therapy and ischemic stroke outcome in the North Dublin Population Stroke Study. Methods-A population-based prospective cohort study was performed using rigorous ascertainment methods. Prestroke and acute (Յ72 hours) poststroke medications were recorded. Modified Rankin score and fatality were assessed at 7, 28, and 90 days and 1 year. Results-Of 448 ischemic stroke patients, statins were prescribed before stroke onset in 30.1% (134/445) and were begun acutely (Յ72 hours) in an additional 42.5% (189/445). On logistic regression analysis, adjusting for age, prestroke disability (modified Rankin scale), NIHSS score, hypertension, and aspirin, new poststroke statin therapy was independently associated with improved early and late survival (compared with statin untreated patients: OR for death, 0.12; CI, 0.03-0.54 at 7 days; OR, 0.19; CI, 0.07-0.48 at 90 days; OR, 0.26; CI, 0.12-0.55 at 1 year; PՅ0.006 for all). Similar findings were observed for statin therapy before stroke onset (adjusted OR for death compared with statin-untreated-patients, 0.04; CI, 0.00 -0.33; Pϭ0.003 at 7 days; OR, 0.23; CI, 0.09 -0.58; Pϭ0.002 at 90 days; OR, 0.48; CI, 0.23-1.01; Pϭ0.05 at 1 year). Conclusions-Statin therapy at stroke onset and newly begun statins were associated with improved early and late outcomes, supporting data from experimental studies. Randomized trials of statin therapy for treatment of acute stroke are needed. (Stroke. 2011;42:1021-1029.)Key Words: acute prescription Ⅲ acute stroke Ⅲ neuroprotectants Ⅲ outcomes Ⅲ statins I n randomized trials, 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitors (statins) prevent stroke in survivors of first stroke and in other patients at high risk with vascular disease. 1,2 Statins also may improve outcomes after stroke. Infarct volume is reduced by pretreatment or early introduction of statin therapy in experimental acute stroke models. [3][4][5][6][7][8][9] In rodents, statin pretreatment has been associated with reduced neurological disability after focal brain ischemia. 4 -6 Rats treated with atorvastatin 24 hours after focal ischemia had enhanced neurological function, angiogenesis, synaptogenesis, and neuronal progenitor cell migration in the periinfarct region compared to controls. 10 Experimental data Continuing medical education (CME) credit is available for this article. Go to http://cme.ahajournals.org to take the quiz. Received July 12, 2010; accepted November 9, 2010 suggest that statins have vasodilatory, antithrombotic, antiinflammatory, antioxidant, and neuroprotective effects, which may mediate these benefits. 5-7,9 -11 Although providing some support for a neuroprotective role of statins in acute stroke, findings from clinical studies have been inconsistent. Whereas some observational studies have reported reduced mortality or improved functional outcomes in patients treated with statins before stroke on...

Background and Purpose-The World Health Organization has emphasized the importance of international populationbased data for unbiased surveillance of stroke incidence and outcome. To date, few such studies have been conducted using recommended gold-standard ascertainment methods. We conducted a large, population-based stroke study in Dublin, Ireland. Methods-Using gold-standard ascertainment methods, individuals with stroke and transient ischemic attack occurring over a 12-month period (December 1, 2005-November 30, 2006 in North Dublin were identified. Disability was assessed using the modified Rankin score and stroke severity (Ͻ72 hours) by the National Institutes of Health Stroke Scale. Stroke-related deaths were confirmed by review of medical files, death certificates, pathology, and coroner's records. Crude and standardized (to European and World Health Organization standard populations) rates of incidence, risk factors, severity, and early outcome (mortality, case-fatality, disability) were calculated, assuming a Poisson distribution for the number of events. Results-Seven hundred one patients with new stroke or transient ischemic attack were ascertained (485 first-ever stroke patients, 83 recurrent stroke patients, 133 first-ever transient ischemic attack patients). Crude frequency rates (all rates per 1000 person-years) were: 1.65 (95% CI, 1.5-1.79; first-ever stroke), 0.28 (95% CI, 0.22-0.35; recurrent stroke), and 0.45 (95% CI, 0.37-0.53; first-ever transient ischemic attack). Age-adjusted stroke rates were higher than those in 9 other recent population-based samples from high-income countries. High rates of subtype-specific risk factors were observed (atrial fibrillation, 31.3% and smoking, 29.1% in ischemic stroke; warfarin use, 21.2% in primary intracerebral hemorrhage; smoking, 53.9% in subarachnoid hemorrhage; PϽ0.01 for all compared with other subtypes). Compared with recent studies, 28-day case-fatality rates for primary intracerebral hemorrhage (41%; 95% CI, 29.2%-54.1%) and subarachnoid hemorrhage (46%; 95% CI, 28.8%-64.5%) were greater in Dublin. Conclusions-Using gold-standard methods for case ascertainment, we found high incidence rates of stroke in Dublin compared with those in similar high-income countries; this is likely explained in part by high rates of subtype-specific risk factors. (Stroke. 2012;43:2042-2047.)Key Words: acute stroke Ⅲ cerebrovascular disease Ⅲ epidemiology Ⅲ health policy Ⅲ outcomes C ardiovascular diseases are the leading cause of death globally, with almost 6 million deaths attributable to stroke in 2005. 1 Stroke incidence rates are increasing rapidly in lowand middle-income countries, whereas substantial increases in the absolute numbers of individuals affected by stroke are projected in high-income countries, because of lifestyle changes and increasing population life-expectancy. [2][3][4] To develop policy, health-service, and public health measures to address the challenge of increasing global stroke frequency, the World Health Organization has emphasized the ...