Prestroke Statin Use Research Articles

Statins in Acute Ischemic Stroke: A Systematic Review.

Background and PurposeStatins have pleiotropic effects of potential neuroprotection. However, because of lack of large randomized clinical trials, current guidelines do not provide specific recommendations on statin initiation in acute ischemic stroke (AIS). The current study aims to systematically review the statin effect in AIS.MethodsFrom literature review, we identified articles exploring prestroke and immediate post-stroke statin effect on imaging surrogate markers, initial stroke severity, functional outcome, and short-term mortality in human AIS. We summarized descriptive overview. In addition, for subjects with available data from publications, we conducted meta-analysis to provide pooled estimates.ResultsIn total, we identified 70 relevant articles including 6 meta-analyses. Surrogate imaging marker studies suggested that statin might enhance collaterals and reperfusion. Our updated meta-analysis indicated that prestroke statin use was associated with milder initial stroke severity (odds ratio [OR] [95% confidence interval], 1.24 [1.05-1.48]; P=0.013), good functional outcome (1.50 [1.29-1.75]; P<0.001), and lower mortality (0.42 [0.21-0.82]; P=0.0108). In-hospital statin use was associated with good functional outcome (1.31 [1.12-1.53]; P=0.001), and lower mortality (0.41 [0.29-0.58]; P<0.001). In contrast, statin withdrawal was associated with poor functional outcome (1.83 [1.01-3.30]; P=0.045). In patients treated with thrombolysis, statin was associated with good functional outcome (1.44 [1.10-1.89]; P=0.001), despite an increased risk of symptomatic hemorrhagic transformation (1.63 [1.04-2.56]; P=0.035).ConclusionsThe current study findings support the use of statin in AIS. However, the findings were mostly driven by observational studies at risk of bias, and thereby large randomized clinical trials would provide confirmatory evidence.

Effect of pre-stroke statin use on stroke severity and early functional recovery: a retrospective cohort study

BackgroundExperimental studies suggest that pre-stroke statin treatment has a dual effect of neuroprotection during ischemia and neurorestoration after ischemic injury. The aim of this study was to evaluate the effect of pre-stroke statin use on initial stroke severity and early clinical outcome.MethodsWe used a prospective database enrolling patients with acute ischemic stroke from 12 hospitals in Korea between April 2008 and January 2012. Primary endpoint was the initial stroke severity as measured by the National Institutes of Health Stroke Scale (NIHSS) score. Secondary endpoints were good outcome (modified Rankin Scale [mRS], 0–2) and overall mRS distribution at discharge. Multivariable regression model and propensity score (PS) matching were used for statistical analyses.ResultsAmong the 8340 patients included in this study, 964 patients (11.6 %) were pre-stroke statin users. The initial NIHSS score (mean [95 % CI]) was lower among pre-stroke statin users vs. non-users in multivariable analysis (5.7 [5.2–6.3] versus 6.4 [5.9–6.9], p = 0.002) and PS analysis (5.2 [4.7–5.7] versus 5.7 [5.4–6.0], p = 0.043). Pre-stroke statin use was associated with increased achievement of mRS 0–2 outcome (multivariable analysis: OR [95 % CI], 1.55 [1.25–1.92], p < 0.001; PS matching: OR [95 % CI], 1.47 [1.16-1.88]; p = 0.002) and favorable shift on the overall mRS distribution (multivariable analysis: OR [95 % CI], 1.29 [1.12-1.51], p = 0.001; PS matching: OR [95 % CI], 1.31 [1.11-1.54]; p = 0.001).ConclusionsPre-stroke statin use was independently associated with lesser stroke severity at presentation and better early functional recovery in patients with acute ischemic stroke.Electronic supplementary materialThe online version of this article (doi:10.1186/s12883-015-0376-3) contains supplementary material, which is available to authorized users.

Abstract T MP93: Statin Treatment May Reduce the Risk of Post-stroke Infections

Background: Infection is common and likely detrimental after stroke, while the preventive effects of antibiotics are not satisfactory. Statin has been proved to possess pleiotropic neuropretection effects, including the anti-infection function. Previous studies have demonstrated a beneficial effect of statin in treating and preventing different infections, however, whether statin use can reduce the risk of post-stroke infection is not much clear. The purpose of this study is to investigate the influence of statin use on the risk of post-stroke infection. Methods: Consecutive ischemic stroke patients admitted to our Hospital form January 2011 to August 2013 were enrolled. We analyzed vascular risk factors, clinical symptoms(including dysphagia and bladder dysfunction), prestroke treatments(including statins use), laboratory data, stroke severity, interventions in hospital(including nasogastric tube and urethral catheter placement) and the development of infectious complications(pneumonia, urinary tract infection and sepsis). Logistic regression analyses were performed to test the association between statin use and post-stroke infections. Results: A total of 1863 patients were included and 306 patients (16.4%) developed in-hospital infections with the following distribution: 244 cases of pneumonia (13.1%), 52 cases of urinary tract infection (2.8%) and 24 cases of sepsis (1.3%). 1457 patients (78.2%) got statins treatment: 129 started before stroke (6.9%) and 1328 started in acute phase of stroke (71.3%). Univariate analysis showed that statin use in acute phase was related to a lower risk of post-stroke infections (P&lt;0.001). After adjusting for age, gender, NIHSS, dysphagia, bladder dysfunction, nasogastric tube and urethral catheter placement, this relationship remained significant (OR 0.56; 95% CI, 0.38-0.82; P=0.003). However, prestroke statin use was not found to reduce the risk of post-stroke infections both in univariate (P=0.06) and multivariate analysis (P=0.20). Conclusions: Statin use in acute phase of ischemic stroke may reduce the risk of post-stroke infections.

Prestroke statins, progression of white matter hyperintensities, and cognitive decline in stroke patients with confluent white matter hyperintensities.

Cerebral white matter hyperintensities (WMH) are a consequence of cerebral small vessel disease. Statins have been shown to reduce recurrent stroke among patients with various stroke subtypes, including lacunar stroke, which also arises from small vessel disease. In this study, we investigated the hypothesis that prestroke statin use would reduce the progression of WMH and/or cognitive decline among stroke patients with confluent WMH. Patients (n = 100) were participants of the VITAmins To Prevent Stroke magnetic resonance imaging substudy. All patients had confluent WMH on magnetic resonance imaging at baseline. Eighty-one patients completed the 2-year follow-up. We assessed general cognition and executive function using the mini-mental state examination and Mattis dementia rating scale-initiation/perseveration subscale, respectively. We compared the change in volume of WMH and cognition between prestroke statin use and prestroke nonstatin use groups. We also evaluated the effects of prestroke statin use on incident lacunes and microbleeds. The prestroke statin use group (n = 51) had less WMH volume progression (1.54 ± 4.52cm(3) vs 5.01 ± 6.00cm(3), p = 0.02) compared with the prestroke nonstatin use group (n = 30). Multivariate linear regression modeling identified prestroke statin use as an independent predictor of WMH progression (β = -0.31, p = 0.008). Prestroke statin use was also associated with less decline (Mattis dementia rating scale-initiation/perseveration subscale; β = 0.47, p = 0.001). No association was observed with changes in mini-mental state examination scores. There were no between group differences on incident lacunes or incident microbleeds. Prestroke statin use may reduce WMH progression and decline in executive function in stroke patients with confluent WMH.

Abstract 65: Effect of Prestroke Statin Use on Stroke Severity and Early Functional Recovery

Background: Experimental studies suggest that prestroke statin treatment has dual effect of neuroprotection during ischemia and neurorestoration after ischemic injury. However, human clinical stroke studies of small to modest sample sizes have shown inconsistent results regarding these effects. Methods: We analyzed the Clinical Research Center for Stroke-5 data set for patients hospitalized with acute ischemic stroke in 12 academic hospitals between April 1, 2008 and January 31, 2012. Primary endpoint was the initial stroke severity as measured by the National Institutes of Health Stroke Scale (NIHSS) score. Secondary endpoints were mRS 0-2 proportion and overall distribution of mRS outcomes at discharge. Propensity score (PS) analysis were used to adjust baseline characteristics between statin users and non-users in addition to multivariable analyses. Results: Among 8,340 patients included in this study (age, 67±13 years; men, 59.6%; initial median NIHSS score [interquartile range, IQR], 3 [2-7]), 964 patients (11.6%) were taking statins before the index stroke. Prestroke statin users had significantly lesser initial NIHSS score than that of non-users (unadjusted mean [95% CI], 4.6 [4.3-4.9] versus 5.4[5.3-5.6], p &lt;0.0001; median [IQR]), 3 (IQR, 1-6) versus 3 (IQR, 2-7) , p &lt;0.0001).The difference remained significant after adjustment for covariates (adjusted mean, 6.0 [5.5-6.5] versus 6.6 [6.1-7.0]; p=0.0062) as well as PS-matched cohort (adjusted mean, 4.8[4.3-5.2] versus 5.4[5.1-5.7], p=0.0298). After adjusting for covariates including initial NIHSS score, statin users had more frequent mRS 0-2 outcome (adjusted OR [95% CI], 1.50 [1.21-1.86]; p=0.0002) and greater favorable shift on the mRS score at discharge than those of non-users (adjusted OR [95% CI], 1.26 [1.08-1.48]; p=0.003). In PS-matched cohort, similar associations were also found for dichotomized outcomes (adjusted OR [95% CI], 1.55 [1.22-1.97]; p=0.0003) and for ordinal outcomes (adjusted OR [95% CI], 1.28 [1.07-1.52]; p=0.0058). Conclusions: Prestroke statin use was independently associated with lesser stroke severity at presentation and better early functional outcome, suggesting dual effect of neuroprotection and neurorestoration in human clinical strokes.

Role of Statin in Atrial Fibrillation-Related Stroke: An Angiographic Study for Collateral Flow

Background: Currently, intensive lipid lowering is recommended in patients with atherosclerotic ischemic stroke or transient ischemic attack. However, the role of statin in cardioembolic stroke is unclear. We investigated the association of statin with pretreatment collateral status in cardioembolic stroke. Methods: A collaborative study from two stroke centers in distinct geographic regions included consecutive patients with acute middle cerebral artery (MCA) infarction due to atrial fibrillation (AF) who underwent cerebral angiography. The relationship between pretreatment collateral grade and the use/dose of statin at stroke onset was assessed. The angiographic collateral grade was evaluated according to the ASITN/SIR Collateral Flow Grading System. Results: Ninety-eight patients (76 statin-naïve, 22 statin users) were included. Compared with statin-naïve patients, statin users were older and more frequently had hypertension, hyperlipidemia and coronary heart disease. Excellent collaterals (grade 3-4) were more frequently observed in statin users (11 patients, 50%) than in statin-naïve patients (21 patients, 27.6%; p = 0.049). The use of atorvastatin 10 mg equivalent or higher doses of statin was associated with excellent collaterals (p for trend = 0.025). In multiple regression analysis, prestroke statin use was independently associated with excellent collaterals (odds ratio, 7.841; 95% confidence interval, CI, 1.96-31.363; p = 0.004). Conclusions: Premorbid use of statin in AF patients is associated with excellent collateral flow. Although most statin trials excluded patients with cardioembolic stroke, our data suggests the possibility that statin may be beneficial in AF-related stroke.

Association of Prestroke Statin Use and Lipid Levels With Outcome of Intracerebral Hemorrhage

It is unclear whether blood lipid profiles and statin use before intracerebral hemorrhage (ICH) are associated with its outcome. The Helsinki ICH Study, a single-center observational registry of consecutive ICH patients, was used to study the associations between premorbid statin use, baseline lipid levels, and clinical outcome. The registry includes 964 ICH patients. Statin users (n=187; 19%) were significantly older, had more frequent comorbidities and medication, lower lipid levels, and higher admission Glasgow Coma Scale compared with nonusers. Modified Rankin Scale at discharge or mortality did not differ between statin users and nonusers. Compared with survivors, significantly lower total cholesterol and low-density lipoprotein cholesterol levels were observed in patients who died in hospital (median, 4.1 mmol/L [interquartile range, 3.6-4.4] versus 4.5 [3.8-5.1]; P<0.01; 1.9 mmol/L [1.4-2.5] versus 2.4 [1.8-3.0]; P<0.001, respectively), at 3 or 12 months. After adjusting for known ICH prognostic factors based on univariate analysis that is, age, National Institutes of Health Stroke Scale, Glasgow Coma Scale, ICH volume, and intraventricular location, lower low-density lipoprotein levels were independently associated with in-hospital mortality (odds ratio, 0.54 [95% confidence interval, 0.31-0.93]; P=0.028). Premorbid statin use did not affect the outcome of ICH, but lower low-density lipoprotein levels were associated with higher in-hospital mortality.

Statin Therapy and Outcome After Ischemic Stroke

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. 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. 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, 0.67-0.95; 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). 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. Randomized trials of statin therapy in acute ischemic stroke are needed.

Low Cholesterol, Statins and Outcomes in Patients with First-Ever Acute Ischemic Stroke

Background: High cholesterol has been associated with better stroke outcomes. Conversely, a protective effect of prestroke statin use in the acute phase of stroke has been reported. The effect of low cholesterol on outcome in patients with and without prestroke statin treatment has not been studied. We assessed the association between low cholesterol and ischemic stroke short- and long-term outcomes and studied potential interactions with statin treatment in patients with a first-ever ischemic stroke in a prospective national registry. Methods: Ischemic stroke patients in the National Acute Stroke Israeli (NASIS) registry with a first-ever stroke and no previous disability, dementia or cancer admitted in all hospitals nationwide during 2-month periods in 2004, 2007 and 2010 were included (n = 1,895). Cholesterol levels ≤155 mg/dl (1st quintile) were defined as low cholesterol and patients treated with statins for at least 7 days before stroke onset were categorized as prestroke statin treated. Severe stroke (NIHSS ≥11), total anterior circulation infarction, poor functional outcome (defined as discharged to a nursing facility or modified Rankin Scale >3 or death), and mortality at discharge and at 3 years were the study outcomes. Associations between low cholesterol and outcomes at discharge were assessed separately in patients with and without prestroke statin treatment using multiple logistic regression analyses. Mortality at 3 years was assessed in a subset of 681 patients with Cox proportional hazard models. Results: Patients were 67.4 ± 13.5 years old on average; 43.1% were women. Low cholesterol was associated with higher rates of stroke risk factors. Controlling for age, sex, hypertension, diabetes, current smoking, ischemic heart disease, congestive heart failure and atrial fibrillation, low cholesterol was significantly associated with severe stroke, total anterior circulation infarction and poor functional outcome in patients with and without statin treatment. There were no interactions between low cholesterol and prestroke statin therapy in association with outcomes. Short- and long-term mortality rates were increased for patients with low cholesterol (5.2% at discharge and 35% at 3-years) compared with higher levels (2.5% at discharge and 20.5% at 3 years). Adjusted mortality risks were increased for patients with low cholesterol; however, this finding was statistically significant only for patients not on statins before the stroke. Conclusions: Low cholesterol is associated with increased stroke severity and poorer functional outcome in patients with and without prestroke statin use. Low-cholesterol statin-naive patients show increased risks of mortality. ‘Reverse epidemiology’ in the association between cholesterol and outcome is possible in patients with ischemic stroke.

Effect of previous statin therapy on severity and outcome in ischemic stroke patients: a population-based study

Although statin therapy has been shown to be effective in the prevention of ischemic stroke, its effect on stroke severity and early outcome is still controversial. We aimed to evaluate the association between statin use before onset and both initial severity and functional outcome in ischemic stroke patients. All cases of first-ever ischemic stroke that occurred in Dijon, France (151,000 inhabitants) between 2006 and 2011 were prospectively identified from the Dijon Stroke Registry. Vascular risk factors, clinical severity at onset assessed by the NIHSS score, stroke subtypes, prestroke statin use, and lipid profile were collected. Functional outcome was defined by a six-level categorical outcome using the modified Rankin scale. Analyses were performed using ordinal logistic regression models. Among the 953 patients with first-ever ischemic stroke, 127 (13.3 %) had previously been treated with statins. Initial stroke severity did not differ between statin users and non-users [median NIHSS score (interquartile range) 4.0 (7.0) versus 4.0 (9.0) p = 0.104]. In unadjusted analysis, statin use was associated with a lower risk of an unfavorable functional outcome at discharge (OR 0.69; 95 % CI 0.49-0.96; p = 0.026) that was no longer significant in multivariate analyses (OR 0.76; 95 % CI 0.53-1.09; p = 0.134). After adjustment for admission plasma LDL cholesterol levels, the non-significant association was still observed (OR 0.76; 95 % CI 0.49-1.18; p = 0.221). This population-based study showed that prestroke statin therapy did not affect initial clinical severity but was associated with a non-significant better early functional outcome after ischemic stroke.

Statin Treatment and Functional Outcome After Ischemic Stroke

Multiple studies suggest that statin use before acute ischemic stroke is associated with improved functional outcome. However, available evidence is conflicting, and several published reports are limited by small sample sizes. We therefore investigated the effect of antecedent use of statins on stroke outcome by performing a meta-analysis of all results from published studies as well as our own unpublished data. We performed a systematic literature search and meta-analysis of studies investigating the association between prestroke statin use and clinical outcome and included additional data from 126 prestroke statin users and 767 nonusers enrolled at our institution. A total of 12 studies, comprising 2013 statin users and 9682 nonusers, was meta-analyzed using a random effects model. We also meta-analyzed results for individual Trial of ORG 10172 in Acute Stroke Treatment stroke subtypes to determine whether the effect of statin use differed across subtypes using the Breslow-Day test. Meta-analysis of all available data identified an association between prestroke statin use and improved functional outcome (OR, 1.62; 95% CI, 1.39 to 1.88), but we uncovered evidence of publication bias. The effect of statin use on functional outcome was found to be larger for small vessel strokes compared with other subtypes (Breslow-Day P=0.008). Antecedent use of statins is associated with improved outcome in patients with acute ischemic stroke. This association appears to be stronger in patients with small vessel stroke subtype. However, evidence of publication bias in the existing literature suggests these findings should be interpreted with caution.

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We evaluated whether pre- and post-stroke statin use was associated with intracranial hemorrhage (ICH) and clinical outcome at 3 months after intravenous recombinant tissue plasminogen activator (IV rt-PA) for acute ischemic stroke. This study enrolled 600 consecutive patients (72 +/- 12 years, woman 37.2%) who received IV rt-PA at ten stroke centers that participated in the SAMURAI rt-PA Registry from October 2005 to July 2008. Statins were used prior to stroke in 112% and within 72 h after IV rt-PA in 10.0% of patients. One hundred nineteen patients (19.8%) developed ICH. Pre-stroke statin use was not an independent factor associated with ICH (OR 1.46; 95% CI 0.76-2.81, p = 0.225). Of 535 patients with a premorbid mRS < or = 1, 199 (37.2%) had a favorable clinical outcome at 3 months (mRS < or = 1). Pre-stroke statin use (OR 1.05; 95% CI 0.55-2.01, p = 0.879), as well as post-stroke statin use (OR 1.31; 95% CI 0.66-2.59, p = 0.440), was not an independent predictor of outcome. In patients who received IV rt-PA for acute ischemic stroke, statin use did not increase ICH after thrombolysis, nor was it associated with clinical outcome.

Statin enhancement of collateralization in acute stroke

Collateral circulation influences cerebral infarction occurrence and size. Statins may improve ischemic stroke outcomes. We evaluated the relationship between prestroke statin use and pretreatment angiographic collateral grade among acute ischemic stroke patients presenting with occlusion of a major cerebral artery. After adjusting for covariates, the statin-treated group had significantly higher collateral scores than non-statin users, suggesting an association between statin use and better collateralization during acute stroke.

March 6 Highlights

Bang et al. evaluated the influence of admission cholesterol and prestroke statin use on symptomatic hemorrhagic transformation of brain infarction following recanalization treatment. They found that lower admission low-density lipoprotein cholesterol level with or without statin use was independently associated with greater hemorrhagic risk. see page 737 There is an accompanying editorial by Larry B. Goldstein. see page 719 Engels et al. studied 60 patients with mental retardation by genome-wide array-based comparative genomic hybridization. They identified novel microimbalances as the probable cause of mental retardation in 10% of patients with unclear etiology. Precise breakpoint analyses allowed the identification of …

Cholesterol level and symptomatic hemorrhagic transformation after ischemic stroke thrombolysis

Prestroke statin use may improve ischemic stroke outcomes, yet there is also evidence that statins and extremely low cholesterol levels may increase the risk of intracranial hemorrhage. We evaluated the independent effect of statin use and admission cholesterol level on risk of symptomatic hemorrhagic transformation (sHT) after recanalization therapy for acute ischemic stroke. We analyzed ischemic stroke patients recorded in a prospectively maintained registry that received recanalization therapies (IV or intra-arterial fibrinolysis or endovascular embolectomy) at a university medical center from September 2002 to May 2006. The independent effect of premorbid statin use on sHT post intervention was evaluated by logistic regression, adjusting for prognostic and treatment variables known to predict increased HT risk after ischemic stroke. Among 104 patients, mean age was 70 years, and 49% were men. Male sex, hypertension, statin use, low total cholesterol and low-density lipoprotein (LDL) cholesterol, current smoking, elevated glucose levels, and higher admission NIH Stroke Scale (NIHSS) score were all associated with a greater risk of sHT in univariate analysis. After adjusting for covariates, low LDL cholesterol (odds ratio [OR], 0.968 per 1-mg/dL increase; 95% CI, 0.941 to 0.995), current smoking (OR, 14.568; 95% CI, 1.590 to 133.493), and higher NIHSS score (OR, 1.265 per 1-point increase; 95% CI, 1.047 to 1.529) were independently associated with sHT risk. Lower admission low-density lipoprotein cholesterol level with or without statin use, current smoking, and greater stroke severity are associated with greater risk for symptomatic hemorrhagic transformation after recanalization therapy for ischemic stroke.