Prestroke Statin Research Articles

Effectiveness of statins on outcomes of patients with Embolic Stroke of Undetermined Source (ESUS)

BackgroundStatins are highly recommended as a secondary prevention strategy after a stroke. Embolic Stroke of Undetermined Source (ESUS) accounts for up to one fifth of cases of ischemic stroke. There is a lack of studies investigating the effectiveness of statins in this subgroup of patients. MethodsWe designed a longitudinal cohort study involving patients properly diagnosed with ESUS. Data about statin therapy included information about the time of initiation of the treatment, pre-stroke statin use, statin withdrawal, and the type and dosage of the statin prescribed. Patients were followed for 48 months after the index stroke. The primary endpoints included stroke recurrence, major cardiovascular events, and death from all causes. The secondary endpoint was the functional outcome, assessed in a standardized and systematic way using the modified Rankin Scale (mRS). ResultsPatients who were not taking any statin after ESUS have significantly increased odds of stroke recurrence (OR = 3.29, 95% CI 1.27 – 8.55) or presenting the composite outcome of stroke recurrence, major cardiovascular events, and death (OR = 3.70, 95% CI 1.44 – 9.50) in the multivariate analysis. No statin therapy was directly associated with the functional outcome as well (OR = 3.32, 95% CI = 1.58 – 6.96). The early initiation of the statin therapy was estimated to reduce the risk of a second stroke and the composite outcome by 89% and 87%. ConclusionsOur pioneering study provides evidence that patients with ESUS may benefit from statin therapy, especially if prescribed early and at higher dosages.

Differential association between apolipoprotein B and LDL cholesterol and cerebral atherosclerosis according to pre-stroke statin use

Background and aimsTo reduce cardiovascular risk, low-density lipoprotein cholesterol (LDL-C) is the primary target of statin treatment, while apolipoprotein B (ApoB) is secondary. We investigated the association between atherosclerotic stenosis and LDL-C or ApoB levels and whether a difference in association exists according to pre-admission statin use in ischemic stroke patients. MethodsThis retrospective cross-sectional study included consecutive patients with acute ischemic stroke or transient ischemic attack who underwent lipid profile and angiographic testing. Patients were categorized into four groups according to stenosis location: normal, extracranial atherosclerotic stenosis (ECAS), intracranial atherosclerotic stenosis (ICAS), or ECAS + ICAS. Subgroup analyses were performed by pre-admission statin use. ResultsOf the 6338 patients included, 1980 (31.2%) were in the normal group, 718 (11.3%) in the ECAS group, 1845 (29.1%) in the ICAS group, and 1795 (28.3%) in the ECAS + ICAS group. Both LDL-C and ApoB levels were associated with every location of stenosis. A significant interaction was found between pre-admission statin use and LDL-C level (p for interaction <0.05). LDL-C was associated with stenosis only in statin-naïve patients, whereas ApoB was associated with ICAS, with or without ECAS, in both statin-naïve and statin-treated patients. ApoB also showed a consistent association with symptomatic ICAS in both statin-treated and statin-naïve patients, whereas LDL-C did not. ConclusionsApoB was consistently associated with ICAS, particularly symptomatic stenosis, in both statin-naïve and statin-treated patients. The close association between ApoB levels and residual risk in statin-treated patients could be partially explained by these results.

Abstract P598: Highly Purified Eicosapentaenoic Acid Use Can Reduce Neurological Severity at the Onset of Ischemic Stroke in Patients With Hyperlipidemia

Introduction: Functional outcomes after acute ischemic stroke (AIS) are related to initial neurological severity (NS). Therefore, neuroprotective drugs against ischemic injury are promising. Not only statins but also eicosapentaenoic acid (EPA) have neuroprotective effects. Hypothesis: Highly purified EPA (hp-EPA) pre-stroke may reduce NS at the onset of AIS. Methods: We retrospectively included patients with AIS and hyperlipidemia admitted to our institution between July 2012 and March 2019 from the prospectively and consecutively enrolled institutional stroke registry database. Hyperlipidemia was defined as serum values of low-density lipoprotein cholesterol (LDL-C) at arrival ≥140 mg/dl or triglycerides ≥150 mg/dl. We excluded patients: (1) admitted to our institution 24 h after AIS onset, (2) who did not stay in the hospital, and (3) in whom dyslipidemia drugs pre-stroke except the hp-EPA were administered. We collected data on age; sex; pre-stroke statin use, antiplatelets, anticoagulants, antihypertensives, and antidiabetic drugs; serum albumin, glucose, glycated hemoglobin (HbA1c), cholesterol, triglycerides, and c-reactive protein levels; pre-stroke modified Rankin scale and the National Institutes of Health Stroke Scale (NIHSS) scores; stroke subtypes at admission; hospitalizations; and home discharge. We performed a multivariable linear regression analysis to identify significant variables of NIHSS scores at arrival. Results: Of the 2,199 patients with AIS and hyperlipidemia during the study period, 691 met our inclusion and exclusion criteria, their median age was 75 years, and 18 (2.6%) received pre-stroke hp-EPA. In patients with and without pre-stroke EPA use, the median NIHSS scores were one and three, respectively. Multivariable regression analysis showed that the glucose, mRS, age, LDL-C, and anticoagulants increased the NIHSS score, albumin, HbA1c, high-density lipoprotein cholesterol, antihypertensives, antidiabetic drugs, and hp-EPA use decreased the NIHSS score. Conclusion Pre-stroke hp-EPA use reduced NS at the AIS onset in patients with hyperlipidemia and without other dyslipidemia drugs.

Pre-Stroke Statin Use Is Associated with Mild Neurological Deficits at the Onset of Acute Ischemic Stroke.

Pre-stroke statin use reduces infarct size. Therefore, this retrospective study aimed to investigate whether pre-stroke statin use is associated with mild neurological deficits (mND) at the onset of acute ischemic stroke (AIS). We included patients with AIS admitted to our institution within 24 h of stroke onset between 2011 and 2019. We collected data on age, sex, pre-stroke use of statins, the National Institutes of Health Stroke Scale (NIHSS) score, the serum biomarker levels, and stroke subtypes at admission. In addition, we defined mND as an NIHSS score ≤3 points. We conducted a logistic regression analysis using variables for pre-stroke statin initiation, calculated the propensity scores for pre-stroke statin use, and implemented propensity score matching (PSM). Finally, we used the McNemar test to evaluate whether pre-stroke statin administration significantly affected mND. Of 4370 patients, 2615 met our inclusion criteria. Among the 594 patients with pre-stroke statin use, 308 presented with mND. After PSM, 555 patients received pre-stroke statin treatment, while 286 patients with pre-stroke statin use presented with mND at admission (p = 0.0411). The binary matched pairs contingency table of mND was not symmetrical (p = 0.0385). Pre-stroke statin use is thus associated with mND at the onset of AIS.

Abstract 9448: Pre-Stroke Statin Use is Associated With Mild Neurological Symptoms at the Onset of Acute Ischemic Stroke

Introduction: Statins have protective effects against ischemic injury, and pre-stroke statin use augments cerebral blood flow, reduces infarct size, and improves neurological function in mice. Hypothesis: Pre-stroke statin is associated with mild neurological symptoms at the onset of acute ischemic stroke (AIS). Methods: We retrospectively included patients with AIS admitted to our institution within 24 hours of onset between April 2011 and March 2019. We collected data on age, sex, pre-stroke use of stains, antiplatelets, anticoagulants, antihypertensive drugs, and diabetes drugs, the National Institutes of Health Stroke Scale (NIHSS) score, serum levels of albumin, glucose, glycated hemoglobin, lipids, and c-reactive protein, and stroke subtypes at admission. In addition, we defined mild neurological symptoms (mNS) as the NIHSS score of three or less. We compared variables between patients with and without pre-stroke statins and identified variables with significant differences between them. We conducted a logistic regression analysis using variables for pre-stroke statin use except for the NIHSS score, mNS, lipids, or stroke subtypes, calculated propensity scores for a pre-stroke statin and implemented a one-to-one propensity score matching (PSM). We evaluated differences between matched pairs and whether pre-stroke statin was significant for mNS at admission. We used the McNemar test to evaluate symmetry on a binary matched pairs contingency table of mNS. Results: Two thousand six hundred fifteen patients met our inclusion criteria during the study period. In 594 patients (22.7%) with pre-stroke statins and 2021 patients without them, 308 (51.9%) and 895 (44.3%) patients presented mNS (p=0.0012). After one-to-one PSM, 555 patients underwent pre-stroke statin treatment, and 555 patients did not undergo it. There were no differences in variables between matched pairs except for the NIHSS score, mNS, or cholesterol levels; 286 patients with pre-stroke stains and 252 patients without them presented mNS at admission (p=0.0411), and the binary matched pairs contingency table of mNS was not symmetrical (p=0.0385). Conclusions: Pre-stroke statin use is associated with mNS at the onset of AIS.

Differential influences of LDL cholesterol on functional outcomes after intravenous thrombolysis according to prestroke statin use

This study aimed to elucidate whether low-density lipoprotein cholesterol (LDL-C) levels differentially affect functional outcomes after intravenous thrombolysis (IVT) depending on prestroke statin use. Patients with acute ischemic stroke treated with IVT were categorized into low, intermediate, and high LDL-C groups based on LDL-C levels at admission (< 100/100–130/ > 130 mg/dl, respectively). Multivariable logistic regression analyses were performed to explore the relationships between LDL-C and clinical outcomes (good outcomes at 3 months, modified Rankin Scale scores 0–2). The interaction between LDL-C levels and prestroke statin use regarding functional outcomes was investigated. Among the 4711 patients (age, 67 ± 12 years; males, 62.1%) who met the eligibility criteria, compared with the high LDL-C group, the low and intermediate LDL-C groups were not associated with good outcomes at 3 months according to the multivariable analysis. A potential interaction between the LDL-C group and prestroke statin use on good outcomes at 3 months was observed (Pinteraction = 0.07). Among patients with prestroke statin use, low (aOR 1.84 [1.04–3.26]) and intermediate (aOR 2.31 [1.20–4.47]) LDL-C groups were independently associated with a greater likelihood of having a 3-month good outcome. Our study showed that LDL-C was not associated with a 3-month good outcome, but prestroke statin use could modify the influence of LDL-C levels on functional outcomes after IVT.

A register-based study on associations between pre-stroke physical activity and cognition early after stroke (part of PAPSIGOT)

The objective was to investigate if pre-stroke physical activity is associated with intact cognition early after stroke. The study design was a cross-sectional, register-based study. The study sample included 1111 adults with first stroke (mild or moderate severity) admitted to three Swedish stroke units. The main outcome was cognition. The associations of pre-stroke physical activity, age, sex, smoking, diabetes, atrial fibrillation, previous TIA, statin treatment, hypertension treatment, reperfusion therapies, stroke severity, and education on the outcome cognition were analyzed using binary logistic regression. Physical activity was assessed within 48 h of admittance, and cognition was screened during stroke unit care. The results were: mean age 70 years, 40% women, 61% pre-stroke physically active, and 53% with post-stroke cognitive impairment. Patients with pre-stroke light or moderate physical activity have higher odds for intact cognition compared to inactive: odds ratio (95% confidence interval) 1.32 (0.97-1.80) and 2.04 (1.18-3.53), respectively. In addition to pre-stroke physical activity, people with younger age, a higher level of education, less severe stroke (more mild than moderate), being non-diabetic, and non-smoking have higher odds for intact cognition. In conclusion physical activity before stroke is associated with intact cognition in patients with mild and moderate stroke.

Association of ischemic stroke onset time with presenting severity, acute progression, and long-term outcome: A cohort study.

Preclinical data suggest circadian variation in ischemic stroke progression, with more active cell death and infarct growth in rodent models with inactive phase (daytime) than active phase (nighttime) stroke onset. We aimed to examine the association of stroke onset time with presenting severity, early neurological deterioration (END), and long-term functional outcome in human ischemic stroke. In a Korean nationwide multicenter observational cohort study from May 2011 to July 2020, we assessed circadian effects on initial stroke severity (National Institutes of Health Stroke Scale [NIHSS] score at admission), END, and favorable functional outcome (3-month modified Rankin Scale [mRS] score 0 to 2 versus 3 to 6). We included 17,461 consecutive patients with witnessed ischemic stroke within 6 hours of onset. Stroke onset time was divided into 2 groups (day-onset [06:00 to 18:00] versus night-onset [18:00 to 06:00]) and into 6 groups by 4-hour intervals. We used mixed-effects ordered or logistic regression models while accounting for clustering by hospitals. Mean age was 66.9 (SD 13.4) years, and 6,900 (39.5%) were women. END occurred in 2,219 (12.7%) patients. After adjusting for covariates including age, sex, previous stroke, prestroke mRS score, admission NIHSS score, hypertension, diabetes, hyperlipidemia, smoking, atrial fibrillation, prestroke antiplatelet use, prestroke statin use, revascularization, season of stroke onset, and time from onset to hospital arrival, night-onset stroke was more prone to END (adjusted incidence 14.4% versus 12.8%, p = 0.006) and had a lower likelihood of favorable outcome (adjusted odds ratio, 0.88 [95% CI, 0.79 to 0.98]; p = 0.03) compared with day-onset stroke. When stroke onset times were grouped by 4-hour intervals, a monotonic gradient in presenting NIHSS score was noted, rising from a nadir in 06:00 to 10:00 to a peak in 02:00 to 06:00. The 18:00 to 22:00 and 22:00 to 02:00 onset stroke patients were more likely to experience END than the 06:00 to 10:00 onset stroke patients. At 3 months, there was a monotonic gradient in the rate of favorable functional outcome, falling from a peak at 06:00 to 10:00 to a nadir at 22:00 to 02:00. Study limitations include the lack of information on sleep disorders and patient work/activity schedules. Night-onset strokes, compared with day-onset strokes, are associated with higher presenting neurologic severity, more frequent END, and worse 3-month functional outcome. These findings suggest that circadian time of onset is an important additional variable for inclusion in epidemiologic natural history studies and in treatment trials of neuroprotective and reperfusion agents for acute ischemic stroke.

Abstract TP146: The Effect Of Statins On Thrombus Composition Retrieved By Mechanical Thrombectomy In Acute Ischemic Stroke

Introduction: Ample evidence exists in support of the anti-inflammatory properties of statins which in turn could affect arterial thrombosis. Compositional analysis of thrombi retrieved by MT may provide us with knowledge useful for evaluating the effect of current Statin therapy on thrombus composition. Methods: Consecutive AIS-LVO patients were included. Histopathological evaluation of thrombi retrieved during MT was performed using Martius Scarlet Blue staining (MSB) and immunohistochemistry for von Willebrand Factor (vWF) and anti-citrulinated H3 (CitH3; NETs marker) and the composition of thrombi was determined using image analysis software. Thrombus was considered rich in a given composition if that composition was higher than its overall mean. We reviewed patient’s medication records and cataloged any statin therapy prior to MT. Results: 117 patients were included in this study. The mean density of red blood cells (RBCs), white blood cells (WBCs), platelets (PLT), fibrin (FIB), vWF and NETs (CitH3) in thrombi was 43.4%, 3.7%, 23.6%, 29.3%, 14.3% and 21.1% respectively. Twenty-seven patients were taking Statins at the time of MT. Statins were not associated with pre-thrombectomy IV-tPA, and stroke etiology (p values: &gt;0.05). There was no association between Statins and thrombi composition and type (p values: &gt;0.05 for all thrombus components and type). Additionally, Statins were not associated with MT outcomes including number of device passes and final mTICI score. Conclusion: Pre-stroke Statin therapy was not associated with differences in thrombus composition.

Statins for the Prevention of Post-Stroke Seizure and Epilepsy Development: A Systematic Review and Meta-Analysis

ObjectivesCerebrovascular disease is the leading cause of seizures and incident epilepsy of known etiology in older adults. Statins have increasingly garnered attention as a potential preventive strategy due to their pleiotropic effects beyond lipid-lowering, which may include neuroprotective and anti-epileptogenic properties. We aim to assess the evidence on statin use for prevention of post-stroke early-onset seizures and post-stroke epilepsy. Materials and methodsWe conducted a systematic review and meta-analysis in accordance with PRISMA guidelines, which was prospectively registered with PROSPERO (CRD42019144916). PubMed and Embase were searched from database inception to 05/2020 for English-language, full-text studies examining the association between statin use in adults and development of early-onset seizures (≤7 days post-stroke) or post-stroke epilepsy. Pooled analyses were based on random-effects models using the inverse-variance method. ResultsOf 182 citations identified, 175 were excluded due to duplication or ineligibility. The 7 eligible publications were all cohort studies from East Asia or South America, with a total of 53,579 patients. Pre-stroke statin use was not associated with post-stroke epilepsy (3 studies pooled: OR 1.14, CI 0.91-1.42). However, post-stroke statin use was associated with lower risk of both early-onset seizures (3 studies pooled: OR 0.36, CI 0.25-0.53), and post-stroke epilepsy (6 studies pooled: OR 0.64, CI 0.46-0.88). ConclusionsReview of 7 cohort studies suggested post-stroke, but not pre-stroke, statin use may be associated with reduced risk of early-onset seizures and post-stroke epilepsy. Further research is warranted to validate these findings in broader populations and better parse the temporal components of the associations.

Pre-Stroke Statin Therapy Improves In-Hospital Prognosis Following Acute Ischemic Stroke Associated with Well-Controlled Nonvalvular Atrial Fibrillation.

Many studies have confirmed the positive effect of statins in the secondary prevention of ischemic stroke. Although several studies have concluded that statins may also be beneficial in patients with atrial fibrillation-related stroke, the results of those studies are inconclusive. Therefore, the aim of this study was to analyze the effect of pre-stroke statin therapy on atrial fibrillation-related stroke among patients with a well-controlled atrial fibrillation. This retrospective multicenter analysis comprised 2309 patients with acute stroke, with a total of 533 patients meeting the inclusion criteria. The results showed a significantly lower neurological deficit on the National Institutes of Health Stroke Scale at hospital admission and discharge in the group of atrial fibrillation-related stroke patients who took statins before hospitalization compared with those who did not (p < 0.001). In addition, in-hospital mortality was significantly higher in the atrial fibrillation-related stroke patients not taking statins before hospitalization than in those who did (p < 0.001). Based on the results of our previous research and this current study, we postulate that the addition of a statin to the oral anticoagulants may be helpful in the primary prevention of atrial fibrillation-related stroke.

Paradoxical effect of statin medication on depressive disorder in first-ever ischemic stroke patients: possible antidepressant-like effect prestroke and the opposite in continuous medication poststroke.

Poststroke depression (PSD) is the most frequent complication after stroke. Statin is a widely used prophylactic for stroke. However, some researchers reported that poststroke statin may lead to a depressive change in stroke patients. We aimed to study the effect of different statin medication timing especially prestroke timing on PSD to adopt appropriate intervention around stroke. Patients with first-ever ischemic stroke were consecutively observed from January 2012 to June 2017. They were grouped by different initiation time of statin treatment. The follow-up endpoints were set to: (1) diagnosis of PSD within 1-year and (2) censor data. Cox regression model adjusted for confounding factors was performed. A total of 1571 patients were included in the analyses, among which 210 (13.4%) were comorbided with PSD, and the median time of the course was 30 (14-98) days. The patients who received both pre- and poststroke statin treatment had 1.99 times (P = 0.037) the hazard faced by patients who did not receive that medication. In contrast, sole statin pretreatment may have the tendency to reduce the risk of PSD. Our findings provide the primary results for the prestroke statin medication. The initiation timing of continuous regular statin treatment ahead of ischemic stroke could have a correlation with a higher risk of PSD.

Prestroke Statins Improve Prognosis of Atrial Fibrillation-Associated Stroke through Increasing Suppressor of Cytokine Signaling-3 Levels

Background: Cerebral infarction associated with atrial fibrillation (AF) has relatively higher mortality and morbidity rates than other types of stroke. Statins are being commonly prescribed to patients with stoke. However, the use of statins in AF-related stroke, especially prestroke, has not been well studied. This study aimed to investigate whether the use of prestroke statins could improve clinical outcomes in patients with AF-related acute ischemic stroke (AIS) and its mechanism. Methods: This prospective study enrolled 453 AF-associated AIS patients from 4 medical centers and divided them into 2 groups based on the statin use before the stroke episode. All patients received comprehensive clinical examinations including 72-h Holter electrocardiogram monitoring and were followed up for 3 months. Plasma suppressor of cytokine signaling-3 (SOCS-3) and matrix metalloproteinase-9 (MMP-9) levels were measured by ELISA on admission and days 3 and 7 after enrollment. The endpoints were death, major disability (modified Rankin Scale score ≥3), and composite outcome (death/major disability) at 3 months after the AIS episode. Results: Plasma SOCS-3 levels were significantly increased and MMP-9 levels decreased in patients in the prestroke statin group on hospital admission and days 3 and 7 after enrollment (p < 0.001). Furthermore, our data suggested that baseline plasma SOCS-3 levels were associated with increased risk of 3-month mortality (adjusted odds ratio [OR], 1.012; 95% confidence interval [CI], 1.006–1.018; p < 0.001) and major disability (adjusted OR, 1.013; 95% CI, 1.007–1.02; p < 0.001). Similarly, baseline plasma MMP-9 levels were also associated with increased risk of 3-month mortality (adjusted OR, 1.037; 95% CI, 1.022–1.053; p < 0.001) and major disability (adjusted OR, 1.038; 95% CI, 1.022–1.55; p < 0.001). Conclusion: Our data suggested that the prestroke use of statins improved the clinical outcomes in AIS patients with AF by upregulating the level of SOCS-3 and reducing the plasma MMP-9 level.

Prestroke statin use enhances collateralization in acute ischemic stroke patients

Statin therapy has been shown to be effective in the prevention of ischemic stroke. In addition, recent studies have suggested that prior statin therapy could lower the initial stroke severity and improve stroke functional outcomes in the event of stroke. It was speculated that prestroke statin use may enhance collateral circulation and result in favorable functional outcomes. The aim of the study was to investigate the association of prestroke statin use with leptomeningeal collaterals and to determine the association of prestroke statin use with stroke severity and functional outcome in acute ischemic stroke patients. We prospectively and consecutively enrolled 239 acute ischemic stroke patients with acute infarction due to occlusion of the middle cerebral artery within 24 h in the neurology department of West China Hospital from May 2011 to April 2017. Computed tomographic angiography (CTA) imaging was performed for all patients to detect middle cerebral artery thrombus; regional leptomeningeal collateral score (rLMCS) was used to assess the degree of collateral circulation; the National Institutes of Health Stroke Scale (NIHSS) was used to measure stroke severity at admission; the modified Rankin scale (mRS) was used to measure outcome at 90 days; and premorbid medications were recorded. Univariate and multivariate analyses were performed. Overall, 239 patients met the inclusion criteria. Fifty-four patients used statins, and 185 did not use statins before stroke onset. Prestroke statin use was independently associated with good collateral circulation (rLMCS > 10) (odds ratio [OR], 4.786; 95% confidence interval [CI], 1.195-19.171; P = 0.027). Prestroke statin use was not independently associated with lower stroke severity (NIHSS score≤14) (OR, 1.955; 95% CI, 0.657-5.816; p = 0.228), but prestroke statin use was independently associated with favorable outcome (mRS score≤2) (OR, 3.868; 95% CI, 1.325-11.289; P = 0.013). Our findings suggest that prestroke statin use was associated with good leptomeningeal collaterals and clinical outcomes in acute ischemic stroke (AIS) patients presenting with occlusion of the middle cerebral artery. However, clinical studies should be conducted to verify this claim.

Abstract WMP120: Pre-stroke Statin Enhancement of Collateralization in Acute Ischemic Stroke

Background: Recent studies suggested that prior statin therapy could lower the initial stroke severity and improve stroke functional outcome in case of stroke onset. It was speculated that pre-stroke statin may enhance collateral circulation and result in favorable functional outcome. This study aimed to investigate the association of pre-stroke statin use with leptomeningeal collaterals in acute ischemic stroke patients. Methods: We prospectively and consecutively enrolled 239 acute ischemic stroke patients with acute infarction due to occlusion of the middle cerebral artery within 24 hours from May 2011 to April 2017. CTA imaging was performed for all patients to detect middle cerebral artery thrombus; regional leptomeningeal collateral score (rLMCS) was used to assess the degree of collateral circulation; admission NIHSS was used to measure stroke severity; modified Rankin scale (mRS) at 90 day was used to measure outcome. Univariate and multivariate analyses were performed. Results: 239 patients met inclusion criteria. 54 patients use statin before stroke onset. Pre-stroke statin use was independently associated with good collateral circulations (rLMCS&gt;10) (OR, 4.786; 95% CI, 1.195 - 19.171; P = 0.027). Pre-stroke statin use was not independently associated with lower stroke severity (NIHSS≤14) (OR, 1.955; 95%CI, 0.657- 5.816; P = 0.228), but pre-stroke statin use was independently associated with good outcome (mRS≤2) (OR, 3.868; 95%CI, 1.325 - 11.289; P = 0.013). Conclusion: Pre-stroke statin use seems enhance collateralization and improve clinical outcomes in patients with acute stroke. However, clinical controlled studies should be used to verify this claim.

Abstract TP164: Statins for the Prevention of Post-Stroke Seizure and Epilepsy Development: A Systematic Review and Meta-Analysis

Introduction: Cerebrovascular disease is the leading cause of seizures and incident epilepsy of known etiology in older adults. As prophylactic use of antiepileptic drugs remains controversial, statins have garnered attention as an alternate preventive strategy due to pleiotropic effects, beyond lipid-lowering, which may include neuroprotective and anti-epileptogenic properties. Our objective was to assess the current evidence on statin use for prevention of post-stroke seizure and post-stroke epilepsy (PSE). Methods: We conducted a systematic review following PRISMA guidelines. Pubmed and Embase were searched from database inception to May 2019 for English-language, full-text experimental, observational analytic, or systematic reviews/meta-analytic studies examining the association between statin use in adults and development of early-onset seizures (ES; seizures ≤7 days after stroke) or PSE. Pooled analyses were based on random-effects models using the inverse-variance method. Results: Of 157 citations, 154 were excluded due to duplication or ineligibility, yielding 3 cohort studies from East Asia. Two studies reported on outcomes of ischemic stroke and 1 on hemorrhagic stroke. Only 1 study reported on ES, finding a significantly reduced risk following post-stroke statin use (OR 0.35, CI 0.20-0.60). Two studies reported on pre-stroke statin use, with findings demonstrating a lack of association with PSE (pooled OR 1.17, CI 0.93-1.48; Figure 1.1). However, post-stroke statin use was associated with less PSE (pooled OR 0.61, CI 0.50-0.74), without evidence of heterogeneity (Figure 1.2). Conclusions: Systematic review and meta-analysis of 3 high-quality cohort studies suggests post-stroke, but not pre-stroke, statin use may be associated with reduced risk of PSE. Further research is warranted to verify if these findings are replicable in other populations, as well as to explore the influence of timing and duration of statin use on outcomes.

Prestroke statins use reduces oxidized low density lipoprotein levels and improves clinical outcomes in patients with atrial fibrillation related acute ischemic stroke

BackgroundAtrial fibrillation (AF) is a common cause of cerebral infarction, which could lead to endothelial dysfunction, increased reactive oxygen species (ROS) and oxidized low density lipoprotein (Ox-LDL).AF is associated with higher mortality and more severe neurologic disability. Statins may exert neuroprotective effects that are independent of LDL-C lowering. The purpose of our study was to investigate whether prestroke statins use could reduce plasma Ox-LDL levels and improve clinical outcomes in patients with AF-related acute ischemic stroke (AIS).MethodsThis was a multicenter prospective study that involved four medical centers, 242 AIS patients with AF were identified, who underwent a comprehensive clinical investigation and a 72 h-Holter electrocardiogram monitoring. All patients were divided into two groups: prestroke statins use and no prestroke statins use groups, who were followed up for 3 months. Plasma Ox-LDL levels were measured using enzyme-linked immunosorbent assay (ELISA) on admission and at 3 months. The outcome was death, major disability (modified Rankin Scale score ≥ 3), and composite outcome (death/major disability) at 3 months after AIS.ResultsOne hundred thirty-six patients were in no prestroke statins use group, and 106 in prestroke statins use group. Plasma Ox-LDL levels were significantly lower in prestroke statins use than in no prestroke statins use on admission and at 3 months (P < 0.001). Plasma Ox-LDL levels on admission were associated with 3-month mortality [adjusted odds ratio (OR), 1.05; 95% confidence interval (CI), 0.99–1.12; P = 0.047]. In fully adjusted models, prestroke statins use was associated with reduced 3-month mortality [adjusted OR, 0.38; 95% CI, 0.16–0.91; P = 0.031)], major disability (adjusted OR, 0.38; 95% CI, 0.15–0.99; P = 0.047), and composite outcome (adjusted OR, 0.31; 95% CI, 0.17–0.74; P = 0.009).ConclusionsPrestroke statins use can reduce plasma Ox-LDL levels and improve clinical outcomes in patients with AF-related AIS.

Statin effects in atrial fibrillation-related stroke: A systematic review and meta-analysis

Effects of statins on atrial fibrillation (AF)-related stroke are not well established. We aimed to evaluate whether statin therapy is associated with mortality and recurrent cardiovascular events after AF-related stroke by conducting a systematic review and meta-analysis of recent observational studies. Electronic databases (PubMed, EMBASE, and Cochrane library) were searched to identify literature investigating the effect of pre- and post-stroke statins on clinical outcomes in AF–related stroke patients. The primary outcome was all-cause mortality. Secondary outcomes were recurrent ischemic stroke, recurrent all-type stroke, myocardial infarction, major adverse cardiovascular events (MACE), and poor functional outcome (mRS 4-6) at discharge. We extracted adjusted hazard ratios (HRs) and 95% confidence interval (95% CI) from multivariable analysis of each study to diminish limitations of observational studies. The pooled estimates on each outcome were acquired. A total of 6 studies were divided into post-stroke statin group (n=5) and pre-stroke statin group (n=2). Post-stroke statin therapy was associated with reduced risk of all-cause mortality (HR, 0.64; 95% CI, 0.55–0.74, I2=13%). Regarding to recurrent ischemic stroke, post-stroke statin was not effective to prevent event (HR, 0.99; 95% CI, 0.80-1.21, I2=21%). There were no significant association between post-stroke statin therapy and risk reduction of recurrent stroke, myocardial infarction, or MACE. Pre-stroke statin use was associated with a low risk of poor functional outcome at discharge (HR, 0.76; 95% CI, 0.60-0.96, I2=9%). In these meta-analyses, statin therapy was associated with risk reduction of all-cause mortality and poor functional outcome in patients with AF-related stroke.

Low-dose statin pretreatment reduces stroke severity and improves functional outcomes.

Pre-stroke statin use reduces stroke severity and improves functional outcomes; however, whether low-dose statins as a primary preventive measure have similar effects on the Chinese population remains unclear. Consecutive cases of ischaemic stroke between May 2011 and January 2017 were retrospectively analysed. The primary endpoints were stroke severity on admission and functional outcomes at 90days. The secondary endpoints were factors related to lower stroke severity on admission. Propensity score matching and logistic regression analyses were performed. Of the 1878 patients, 6.4% and 23.8% were pre-stroke statin users before and after propensity matching, respectively, reducing the National Institutes of Health Stroke Scale (NIHSS) score on admission from 5 (2-9) to 3 (2-4) (P < 0.001). Patients receiving pretreatment with low-dose statins tended to have a better mRS distribution (median mRS score 2 [1-3] vs. 3 [2-4], P = 0.007) and a higher likelihood of favourable functional outcomes (FFOs) at 90days (61 [65.6%] vs. 151 [50.8%], P = 0.005). The logistic regression analysis showed that low-dose statins taken before stroke (odds ratio [OR] = 0.15, 95% confidence interval [CI] = 0.08-0.27, P < 0.001) and being male (OR = 0.81, 95% CI = 0.66-0.99, P = 0.035) were related to a lower stroke severity on admission but not among patients with atrial fibrillation (OR = 1.65, 95% CI = 1.12-2.44, P = 0.012) or elevated white blood cell (WBC) counts (OR = 1.12, 95% CI = 1.08-1.17, P < 0.001). Pretreatment with low-dose statins reduced initial stroke severity, improved functional outcomes at 90days and was independently associated with a lower stroke severity on admission among Chinese patients.

The outcomes of statin therapy in patients with acute ischemic stroke in Taiwan: a nationwide epidemiologic study.

Acute stroke is the third leading cause of death in Taiwan. Although statin therapy is widely recommended for stroke prevention, little is known about the epidemiology of statin therapy after acute ischemic stroke (AIS) in Taiwan. To investigate the effects of statin therapy on recurrent stroke, intracranial hemorrhage (ICH), coronary artery disease (CAD), cost of hospitalization and mortality, we conducted a nationwide population-based epidemiologic study. Cases of AIS were identified from the annual hospitalization discharge diagnoses of the National Health Insurance Research Database with the corresponding International Classification of Diseases, ninth revision codes from January 2001 to December 2010. We divided the AIS patients into three groups: non-statin, pre-stroke statin and post-stroke statin. A total of 422671 patients with AIS (including 365419 cases in the non-statin group, 22716 cases in the pre-stroke statin group and 34536 cases in the post-stroke statin group) were identified. When compared to the non-statin group, both statin groups had a lower recurrent stroke risk [pre-stroke statin: odds ratio (OR) = 0.84; 95% confidence interval (CI) = 0.82-0.87; P < 0.0001; post-stroke statin: OR = 0.89; 95% CI = 0.86-0.91; P < 0.0001], lower ICH risk (pre-statin: OR = 0.75; 95% CI = 0.69-0.82; P < 0.0001; post-stroke statin: OR = 0.75; 95% CI = 0.71-0.81; P < 0.0001), and a lower mortality rate (pre-stroke statin: OR = 0.56; 95% CI = 0.53-0.59; P < 0.0001; post-stroke statin: OR = 0.51; 95% CI = 0.48-0.53; P < 0.0001). In terms of CAD, only the post-statin group had a lower risk (OR = 0.81; 95% CI = 0.79-0.84; P < 0.0001) than the non-statin group. The post-statin group had the lowest 1-year medical costs after index discharge among the three groups. Statin therapy reduced the risks of recurrent stroke, CAD, ICH and the first year mortality in patients after AIS. Treatment with statin therapy after AIS is a cost-effective strategy in Taiwan.