Statins for neuroprotection in spontaneous intracerebral hemorrhage.
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ABSTRACT:
SUBMITTER: Chen CJ
PROVIDER: S-EPMC6937496 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Objectives This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the safety and efficacy of statin treatment in patients with spontaneous intracerebral hemorrhage (ICH). Secondary objectives include exploring the effects of dosage and timing (including continuation, discontinuation, and initiation of statins).
| S-EPMC8829829 | biostudies-literature
Project description:PURPOSE OF REVIEW:We review the current evidence for medical and surgical treatments of spontaneous intracerebral hemorrhage (ICH). RECENT FINDINGS:Therapy with hemostatic agents (e.g. factor VIIa and tranexamic acid) if started early after bleeding onset may reduce hematoma expansion, but their clinical effectiveness has not been shown. Rapid anticoagulation reversal with prothrombin concentrates (PCC) plus vitamin K is the first choice in vitamin K antagonist-related ICH. In ICH related to dabigatran, anticoagulation can be rapidly reversed with idarucizumab. PCC are recommended for ICH related to FXa inhibitors, whereas specific reversal agents are not yet approved. While awaiting ongoing trials studying minimally invasive approaches or hemicraniectomy, the role of surgery in ICH remains to be defined. Therapies targeting downstream molecular cascades in order to prevent secondary neuronal damage are promising, but the complexity and multi-phased nature of ICH pathophysiology is challenging. Finally, in addition to blood pressure control, antithrombotic prevention after ICH has to consider the risk of recurrent bleeding as well as the risk of ischemic events. Treatment of acute ICH remains challenging, and many promising interventions for acute ICH await further evidence from trials.
| S-EPMC5590024 | biostudies-literature
Project description:BACKGROUND AND PURPOSE:Apolipoprotein E (ApoE) genotypes have been associated with lobar intracerebral hemorrhage (ICH). Although statins have been associated with an increased risk of ICH, meta-analyses have not consistently shown a statin-induced risk of ICH. Here, we test whether hypercholesterolemia (HC) and ApoE polymorphisms affect the risk of ICH by statin use. METHODS:The Genetic and Environmental Risk Factors for Hemorrhagic Stroke (GERFHS) study is a prospective, demographically matched case-control study of ICH. A similar study of ICH, Genetic Risks for Medication-Related Hemorrhagic Stroke (GOCHA), was used as a replication cohort. Subjects were classified as normocholesterolemia, HC without statin use, and HC with statin use. Statistical comparisons were performed using Fisher exact test, ?2 tests, and the Breslow-Day test. RESULTS:The discovery cohort consisted of 558 ICH cases and 1444 controls, and the replication cohort consisted of 1020 ICH cases and 382 controls. The association of lower risk for HC was not attenuated by statin use. Statin use was observed to confer a higher risk for lobar ICH in those carrying ApoE4/E4 and ApoE2/E4 genotypes in both discovery and replication cohorts, and a test for interaction showed a trend towards significance (P=0.11 for statin and ApoE4/E4). CONCLUSIONS:Statin use does not seem to attenuate the association of HC with decreased risk for nonlobar ICH. Our data support a gene-by-drug effect for lobar ICH, but larger sample sizes are needed to confirm the association before any clinical change is warranted. CLINICAL TRIAL REGISTRATION URL:http://clinicaltrials.gov. Unique identifier: NCT00930280.
| S-EPMC3873717 | biostudies-literature
Project description:ImportanceLimited evidence is available concerning optimal seizure prophylaxis after spontaneous intracerebral hemorrhage (sICH).ObjectiveTo evaluate which of 4 seizure prophylaxis strategies provides the greatest net benefit for patients with sICH.Design, setting, and participantsThis decision analysis used models to simulate the following 4 common scenarios: (1) a 60-year-old man with low risk of early (≤7 days after stroke) (10%) and late (3.6% or 9.8%) seizures and average risk of short- (9%) and long-term (30%) adverse drug reaction (ADR); (2) an 80-year-old woman with low risk of early (10%) and late (3.6% or 9.8%) seizures and high short- (24%) and long-term (80%) ADR risks; (3) a 55-year-old man with high risk of early (19%) and late (34.8% or 46.2%) seizures and low short- (9%) and long-term (30%) ADR risks; and (4) a 45-year-old woman with high risk of early (19%) and late (34.8% or 46.2%) seizures and high short- (18%) and long-term (60%) ADR risks.InterventionsThe following 4 antiseizure drug strategies were included: (1) conservative, consisting of short-term (7-day) secondary early-seizure prophylaxis with long-term therapy after late seizure; (2) moderate, consisting of long-term secondary early-seizure prophylaxis or late-seizure therapy; (3) aggressive, consisting of long-term primary prophylaxis; and (4) risk guided, consisting of short-term secondary early-seizure prophylaxis among low-risk patients (2HELPS2B score, 0), short-term primary prophylaxis among patients at higher risk (2HELPS2B score, ≥1), and long-term secondary therapy for late seizure.Main outcomes and measuresQuality-adjusted life-years (QALYs).ResultsFor scenario 1, the risk-guided strategy (8.13 QALYs) was preferred over the conservative (8.08 QALYs), moderate (8.07 QALYs), and aggressive (7.88 QALYs) strategies. For scenario 2, the conservative strategy (2.18 QALYs) was preferred over the risk-guided (2.17 QALYs), moderate (2.09 QALYs), and aggressive (1.15 QALYs) strategies. For scenario 3, the aggressive strategy (9.21 QALYs) was preferred over the risk-guided (8.98 QALYs), moderate (8.93 QALYs), and conservative (8.77 QALYs) strategies. For scenario 4, the risk-guided strategy (11.53 QALYs) was preferred over the conservative (11.23 QALYs), moderate (10.93 QALYs), and aggressive (8.08 QALYs) strategies. Sensitivity analyses suggested that short-term strategies (conservative and risk guided) are preferred under most scenarios, and the risk-guided strategy performs comparably to or better than alternative strategies in most settings.Conclusions and relevanceThis decision analytical model suggests that short-term (7-day) prophylaxis dominates longer-term therapy after sICH. Use of the 2HELPS2B score to guide clinical decisions for initiation of short-term primary vs secondary early-seizure prophylaxis should be considered for all patients after sICH.
| S-EPMC8314179 | biostudies-literature
Project description:ObjectiveTo evaluate whether delayed appearance of intraventricular hemorrhage (dIVH) represents an independent entity from intraventricular hemorrhage (IVH) present on admission CT or is primarily related to the time interval between symptom onset and admission CT.MethodsA total of 282 spontaneous intracerebral hemorrhage (ICH) patients, admitted February 2009-March 2014 to the neurological intensive care unit of a tertiary care university hospital, were prospectively enrolled in the ICH Outcomes Project. Multivariate logistic regression was used to determine associations with acute mortality and functional long-term outcome (modified Rankin Scale).ResultsA cohort of 282 ICH patients was retrospectively studied: 151 (53.5%) had intraventricular hemorrhage on initial CT scan (iIVH). Of the remaining 131 patients, 19 (14.5%) developed IVH after the initial CT scan (dIVH). The median times from symptom onset to admission CT were 1.1, 6.0, and 7.4 hours for the dIVH, iIVH, and no IVH groups (Mann-Whitney U test, dIVH vs iIVH, p < 0.001) and median time from onset to dIVH detection was 7.2 hours. The increase in ICH volume following hospital admission was larger in dIVH than in iIVH and no IVH patients (mean 17.6, 0.2, and 0.4 mL). After controlling for components of the ICH score and hematoma expansion, presence of IVH on initial CT was associated with discharge mortality and poor outcome at 3, 6, and 12 months, but dIVH was not associated with any of the outcome measures.ConclusionsIn ICH patients, associated IVH on admission imaging is commonly encountered and is associated with poor long-term outcome. In contrast, dIVH on subsequent scans is far less common and does not appear to portend worse outcome.
| S-EPMC4352099 | biostudies-literature
Project description:Background and purposeStatin use may be associated with improved outcome in intracerebral hemorrhage patients. However, the topic remains controversial. Our analysis examined the effect of prior, continued, or new statin use on intracerebral hemorrhage outcomes using the ERICH (Ethnic/Racial Variations of Intracerebral Hemorrhage) data set.MethodsWe analyzed ERICH (a multicenter study designed to examine ethnic variations in the risk, presentation, and outcomes of intracerebral hemorrhage) to explore the association of statin use and hematoma growth, mortality, and 3-month disability. We computed subset analyses with respect to 3 statin categories (prior, continued, or new use).ResultsTwo thousand four hundred and fifty-seven enrolled cases (mean age, 62 years; 42% females) had complete data on mortality and 3-month disability (modified Rankin Scale). Among those, 1093 cases were on statins (prior, n=268; continued, n=423; new, n=402). Overall, statin use was associated with reduced mortality and disability without any effect on hematoma growth. This association was primarily driven by continued/new statin use. A multivariate analysis adjusted for age and major predictors for poor outcome showed that continued/new statins users had good outcomes compared with prior users. However, statins may have been continued/started more frequently among less severe patients. When a propensity score was developed based on factors that could influence a physician's decision in prescribing statins and used as a covariate, continued/new statin use was no longer a significant predictor of good outcome.ConclusionsAlthough statin use, especially continued/new use, was associated with improved intracerebral hemorrhage outcomes, this effect may merely reflect the physician's view of a patient's prognosis rather than a predictor of survival.
| S-EPMC5659292 | biostudies-literature
Project description:Apoptosis is an important factor during the early stage of intracerebral hemorrhage. MiR-181c plays a key regulatory role in apoptosis. However, whether miR-181c is involved in apoptosis of prophase cells after intracerebral hemorrhage remains unclear. Therefore, in vitro and in vivo experiments were conducted to test this hypothesis. In vivo experiments: collagenase type VII was injected into the basal ganglia of adult Sprague-Dawley rats to establish an intracerebral hemorrhage model. MiR-181c mimic or inhibitor was injected in situ 4 hours after intracerebral hemorrhage. Neurological functional defects (neurological severity scores) were assessed 1, 7, and 14 days after model establishment. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling and western blot assay were conducted 14 days after model establishment. In vitro experiments: PC12 cells were cultured under oxygen-glucose deprivation, and hemins were added to simulate intracerebral hemorrhage in vitro. MiR-181c mimic or inhibitor was added to regulate miR-181c expression. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, luciferase reporter system, and western blot assay were performed. Experimental results revealed differences in miR-181c expression in brain tissues of both patients and rats with cerebral hemorrhage. In addition, in vitro experiments found that miR-181c overexpression could upregulate the Bcl-2/Bax ratio to inhibit apoptosis, while inhibition of miR-181c expression could reduce the Bcl-2/Bax ratio and aggravate apoptosis of cells. Regulation of apoptosis occurred through the phosphoinositide 3 kinase (PI3K)/Akt pathway by targeting of phosphatase and tensin homolog deleted on chromosome ten (PTEN). Higher miR-181c overexpression correlated with lower neurological severity scores, indicating better recovery of neurological function. In conclusion, miR-181c affects the prognosis of intracerebral hemorrhage by regulating apoptosis, and these effects might be directly mediated and regulated by targeting of the PTEN\PI3K/Akt pathway and Bcl-2/Bax ratio. Furthermore, these results indicated that miR-181c played a neuroprotective role in intracerebral hemorrhage by regulating apoptosis of nerve cells, thus providing a potential target for the prevention and treatment of intracerebral hemorrhage. Testing of human serum was authorized by the Ethics Committee of China Medical University (No. 2012-38-1) on February 20, 2012. The protocol was registered with the Chinese Clinical Trial Registry (Registration No. ChiCTR-COC-17013559). The animal study was approved by the Institutional Animal Care and Use Committee of China Medical University (approval No. 2017008) on March 8, 2017.
| S-EPMC7047781 | biostudies-literature
Project description:Differences in the incidence of spontaneous intracerebral hemorrhage (ICH) between ethnicities exist, with an estimated 42% of the variance explained by ethnicity itself. Caucasians have a higher proportion of lobar ICH (LICH, 15.4% of all ICH) than do Asians (3.4%). Alterations in the causal factor exposure between countries justify part of the ethnic variance in ICH incidence. One third of ICH risk can be explained by genetic variation; therefore, genetic differences between populations can partly explain the difference in ICH incidence. In this paper, we review the current knowledge of genetic variants associated with ICH in multiple ethnicities. Candidate gene variants reportedly associated with ICH were involved in the potential pathways of hypertension, vessel wall integrity, lipid metabolism, endothelial dysfunction, inflammation, platelet function, and coagulopathy. Furthermore, variations in APOE (in multiple ethnicities), PMF1/SLC25A44 (in European), ACE (in Asian), MTHFR (in multiple ethnicities), TRHDE (in European), and COL4A2 (in European) were the most convincingly associated with ICH. The majority of the associated genes provide small contributions to ICH risk, with few of them being replicated in multiple ethnicities.
| S-EPMC6321144 | biostudies-literature
Project description:Intracerebral hemorrhage (ICH) is a complex and heterogeneous disease, and there is no effective treatment. Spontaneous ICH represents the final manifestation of different types of cerebral small vessel disease, usually categorized as: lobar (mostly related to cerebral amyloid angiopathy) and nonlobar (hypertension-related vasculopathy) ICH. Accurate phenotyping aims to reflect these biological differences in the underlying mechanisms and has been demonstrated to be crucial to the success of genetic studies in this field. This review summarizes how current knowledge on genetics and epigenetics of this devastating stroke subtype are contributing to improve the understanding of ICH pathophysiology and their potential role in developing therapeutic strategies.
| S-EPMC9223468 | biostudies-literature
Project description:BackgroundGiven an ageing population the incidence of both patients suffering from intracerebral hemorrhage (ICH) and those requiring oral anticoagulation will increase. Up to now there are no results from randomized trials available whether or not, and when, ICH survivors should resume OAC. This review summarizes the most important observational studies, and initiated ongoing trials, to help guiding physicians in daily routine decision making.FindingsSeveral large observational studies and meta-analyses verified that OAC resumption was associated with a significant reduction of thromboembolic complications and mortality without leading to increased rates of recurrent ICH. OAC resumption seemed further associated with improved functional recovery and favorable long-term outcome. Given the general bleeding risk reduction in patients using Non-vitamin K antagonist oral anticoagulants (NOAC) compared to Vitamin-K-antagonist (VKA), NOAC use should also be preferred after ICH, although specific comparative studies are pending. Patients with lobar ICH need special attention as these patients showed increased ICH recurrence rates, why decision making should include extended diagnostic work-up evaluating cerebral microbleed burden, cortical subarachnoid hemorrhage and superficial siderosis. Further, patients with mechanical heart valves need specific consideration as restarting VKA may be unsafe until two weeks, whereas optimal balancing of hemorrhagic with thromboembolic complications may allow earlier re-initiation one week after ICH. In patients with atrial fibrillation, resumption generally should take place between 4 and 8?weeks after ICH depending on a patient's individual risk profile. Left atrial appendage occlusion (LAAO) might represent an alternative strategy in high-risk patients. Ongoing clinical trials will clarify whether OAC resumption versus LAAO versus no antithrombotic therapy may represent the best possible secondary stroke prevention in ICH survivors with atrial fibrillation.ConclusionsAccording to observational data OAC resumption after ICH seems beneficial and safe. Ongoing clinical trials will create evidence regarding treatment effects of pharmaceutical resumption and interventional alternatives. Yet, individual decision making weighing the patient's individual thromboembolic versus hemorrhagic risks remains essential.
| S-EPMC7650131 | biostudies-literature