Risk Of Intracranial Hemorrhage In Patients Research Articles

Comparison of direct oral anticoagulants versus low-molecular-weight heparin in primary and metastatic brain cancers: a meta-analysis and systematic review

BackgroundThe safety and efficacy of direct-acting oral anticoagulants (DOACs) for therapeutic anticoagulation in the setting of primary or metastatic brain cancer is not known. ObjectivesTo conduct a meta-analysis and systematic review of studies that compare the risk of intracranial hemorrhage (ICH) in patients with brain cancer treated with DOACs vs low-molecular-weight heparin (LMWH). MethodsA literature search was conducted using PubMed, EMBASE, and Cochrane databases. Summary statistics were obtained by calculating the risk ratio (RR), and heterogeneity across studies was estimated using the I2 statistic. A total of 10 retrospective studies (n = 1638) met criteria for inclusion. The primary endpoint was the pooled RR for ICH in patients with brain tumors receiving anticoagulation with DOACs compared with those receiving LMWH. Secondary analyses included the risk of fatal ICH in each subgroup. ResultsThe pooled RR for ICH in patients receiving DOACs vs those receiving LMWH was 0.65 (95% CI, 0.36-1.17; P = .15; I2 = 50%). In studies evaluating primary brain cancer, there was a reduction in risk of ICH with DOACs (RR, 0.35; 95% CI, 0.18-0.69; P = .003; I2 = 0%). In patients with metastatic brain cancer, there was no difference in the risk of ICH with the type of anticoagulation (RR, 1.05; 95% CI, 0.71-1.56; P = .80; I2 = 0%). The overall risk of fatal ICH was not different between anticoagulants. ConclusionThe risk of ICH in patients with brain cancer receiving therapeutic anticoagulation varies by anticoagulation agent and diagnosis of primary or metastatic disease.

The risk of intracranial hemorrhage in glioma patients receiving anticoagulant treatment for venous thromboembolism: a bayesian network meta-analysis.

We aimed to perform a Bayesian network meta-analysis to assess the risk of intracranial hemorrhage (ICH) in patients with glioma receiving anticoagulant treatment for venous thromboembolism. The PubMed, Embase and Web of Science databases were searched for relevant publications until September 2022. All studies evaluating the risk of ICH in patients with glioma receiving anticoagulant treatment were included. Bayesian network meta-analysis and pairwise meta-analysis were performed to compare the ICH risk between the anticoagulant treatments. The Cochrane's Risk of Bias Tool and the Newcastle-Ottawa Scale (NOS) were used to evaluate the quality of studies. A total of 11 studies with 1301 patients were included. Pairwise comparisons showed no significant differences excepted with LMWH vs. DOACs (OR: 7.28, 95% CI: 2.11-25.17) and LMWH vs. Placebo (OR: 3.66, 95% CI: 2.15-6.24). For network meta-analysis, significant difference was found between patients treated with LMWH vs. Placebo (OR: 4.16, 95% CI: 2.00-10.14) and LMWH vs. DOACs (OR: 10.13, 95% CI: 2.70-70.19). It seems that LMWH has the highest risk of ICH in glioma patients, while no evidence indicates that DOACs increase the risk of ICH. The use of DOACs may perhaps be a better choice. Further larger studies focusing on the benefit-to-risk ratio are warranted.

Antiplatelet medications and intracranial hemorrhage in patients with primary brain tumors

BackgroundSpontaneous intracranial hemorrhage (ICH) is a frequent and severe consequence of primary brain tumors. The safety of antiplatelet medications in this patient population is undefined. ObjectiveThe primary objective was to determine whether antiplatelet medications are associated with an increased risk of ICH in patients with primary brain tumors. Patients/MethodsWe performed a matched, retrospective cohort study of patients with the diagnosis of primary brain tumor treated at our institution between 2010 and 2021. Radiographic images of all potential ICH events underwent blinded review. The primary end point of the study was the cumulative incidence of ICH at 1 year after tumor diagnosis. Results and ConclusionsA total of 387 patients with primary brain tumors were included in the study population (130 exposed to antiplatelet agents, 257 not exposed). The most common malignancy was glioblastoma (n = 256, 66.1%). Among the intervention cohort, 119 patients received aspirin monotherapy. The cumulative incidence of any ICH at 1 year was 11.0% (95% CI, 5.3-16.6) in those receiving antiplatelet medications and 13.0% (95% CI, 8.5-17.6) in those not receiving antiplatelet medications (Gray test, p = 0.6). The cumulative incidence of major ICH was similar between the cohorts (3.3% in antiplatelet cohort vs 2.9% in control cohort, p = 1.0). This study did not identify an increased incidence of ICH in patients with primary brain tumors exposed to antiplatelet medications.

Abstract 51: Apoe Epsilon 4 And Risk Of Bleeding Patients With Brain Arteriovenous Malformations. A Combined Genetic Study In The Uk Biobank And All Of Us

Background: Patients with brain arteriovenous malformation (AVM) are at risk of intracranial hemorrhage (ICH). The epsilon 2 and 4 alleles within the APOE gene are well-described genetic risk factors for spontaneous, non-traumatic intraparenchymal hemorrhages. We tested the hypothesis that the APOE epsilon variants lead to higher risk of ICH in patients with AVMs. Methods: We conducted a two-stage (discovery and replication) genetic association study using individual-level data from the UK Biobank and the All of Us Research Program. We ascertained AVMs and ICH using validated ICD-9/10 codes. Genome-wide array genotyping was completed using the UK Biobank Axiom Array in the UK Biobank, and Illumina’s Global Diversity Array in All of Us. We used genotypic data on the APOE variants rs429358 and rs7412 to ascertain the epsilon 2 and 4 status. Within each study, we tested for association between APOE epsilon variants and ICH risk using multivariable logistic regression. Results: The discovery phase included 189 UK Biobank participants with an AVM (mean age 57 years, female sex 49%), including 37 (19.6%) that sustained an ICH. After adjusting by age, sex, and race/ethnicity, APOE epsilon 4 was associated with a higher risk of ICH (OR 4.20; 95%CI 1.99-9.25; p<0.001) whereas epsilon 2 was not (p>0.05). These results were replicated in 228 participants with AVMs enrolled in All of Us (mean age 56 years, female sex 66%), including 31 (13.6%) who sustained an ICH, where APOE epsilon 4 was associated with a higher risk of ICH (OR 2.73; 95%CI 1.05-7.22; p=0.038) whereas epsilon 2 was not (p>0.05). Conclusion: Among study participants with AVMs enrolled in two large population studies, the APOE epsilon 4 variants were associated higher risk of sustaining a brain bleed. These results point to shared pathophysiology with spontaneous intraparenchymal hemorrhages and provide support for further research focused on evaluating the role of APOE in risk stratification strategies.

Stains therapy and the risk of all bleeding and intracranial hemorrhage: A meta-analysis of randomized controlled studies.

Statins had been used as a cornerstone in the primary and secondary prevention of cardiovascular disease. Widespread attention had been given to the risk of bleeding, especially intracranial hemorrhage (ICH) in patients receiving statins therapy. This study aimed to determine whether statins treatment was associated with the risk of bleeding and ICH in randomized controlled trials (RCTs). Electronic databases were searched for studies up to September 8, 2022. Articles from RCTs were included in the meta-analysis if they reported the bleeding events associated with the treatment of statins or placebo/nonstatin treatment. The risk ratios (RR) of total bleeding and ICH were pooled from the number of patients with each outcome in the statins and control groups from the included studies. Twenty-nine studies comprising 145,929 individuals (2437 incident bleeding cases) were included in the meta-analysis. After a median follow-up duration of 3.65 years, statins treatment was not associated with the risk of all bleeding (RR=1.03, 95% CI 0.93-1.15). Furthermore, in 26 studies comprising 144,177 participants, after a median follow-up duration of 3.95 years, statins treatment was not associated with the risk of ICH (RR=1.05, 95% CI 0.84-1.31). Although in the subgroup analysis with patients with prior stroke, statins treatment showed an increased risk of ICH (RR=1.47, 95% CI 1.07-2.01), sensitivity analysis showed that the result was unstable, which may be mainly driven by the SPARCL study. Statins therapy is not associated with the risk of all bleeding and ICH. Although a mildly increased risk of ICH in patients with prior stroke is observed, which may be caused by chance finding and warrant further documentation.

Vascular complications in patients with brain tumors.

Venous thromboembolism (VTE) and other vascular events are common in patients with brain tumors, but their optimal management is not firmly established, in large part due to the competing risk of intracranial hemorrhage (ICH) in this population. There is conflicting evidence on whether therapeutic anticoagulation increases the risk of ICH in patients with brain tumors, with several metanalysis and retrospective cohort studies showing an increased risk and others showing no differences. Current guidelines recommend anticoagulating brain tumors patients with VTE with either low-molecular weight heparin (LMWH) or direct oral anticoagulants (DOACs), and several retrospective studies have shown the risk of ICH with DOACs is similar or smaller than with LMWH. An increased risk of VTE exists in a variety of brain tumor types. Most patients with brain tumors and VTE should receive therapeutic anticoagulation, and recent retrospective evidence supports the use of both LMWH and DOACs as effective and relatively safe in this setting. Patients with brain tumors are also at increased risk of other vascular tumor- or treatment-related complications whose optimal management is unclear.

ICH in primary or metastatic brain cancer patients with or without anticoagulant treatment: a systematic review and meta-analysis

AbstractAnticoagulant treatment in patients with primary and metastatic brain cancer is a concern due to risk of intracranial hemorrhage (ICH). We performed a systematic review and meta-analysis to evaluate the risk of ICH in patients with primary or metastatic brain cancer treated with or without anticoagulants. Articles on ICH in patients with primary or metastatic brain cancer treated with or without anticoagulants published up to September 2021 were identified by searching PubMed, EMBASE, and Cochrane Library databases. The primary outcome of this analysis was ICH. Thirty studies were included. Rate of ICH was 13.0% in 1009 patients with metastatic brain cancer and 6.4% in 2353 patients with primary brain cancer (relative risk [RR], 3.26; 95% confidence interval [CI], 2.69-3.94; I2 = 92.8%). In patients with primary brain cancer, ICH occurred in 12.5% and 4.4% of patients treated with or without anticoagulants, respectively (11 studies, 659 treated and 1346 not treated patients; RR, 2.63; 95% CI, 1.48-4.67; I2 = 49.6%). In patients with metastatic brain cancer, ICH occurred in 14.7% and 15.4% (5 studies, 265 treated and 301 not treated patients; RR, 0.92; 95% CI, 0.43-1.93; I2 = 0%). ICH occurred in 8.3% of 172 treated with direct oral anticoagulants (DOACs) and in 11.7% of 278 treated with low-molecular weight heparin (LMWH) (5 studies; RR, 0.44; 95% CI, 0.25-0.79; I2 = 0%). Patients with metastatic brain cancer have a particularly high risk of ICH. Patients with primary brain cancer have an increased risk of ICH during anticoagulation. DOACs are associated with a lower risk of ICH than LMWH.

A New Nomogram for Predicting the Risk of Intracranial Hemorrhage in Acute Ischemic Stroke Patients After Intravenous Thrombolysis.

BackgroundWe aimed to develop and validate a new nomogram for predicting the risk of intracranial hemorrhage (ICH) in patients with acute ischemic stroke (AIS) after intravenous thrombolysis (IVT).MethodsA retrospective study enrolled 553 patients with AIS treated with IVT. The patients were randomly divided into two cohorts: the training set (70%, n = 387) and the testing set (30%, n = 166). The factors in the predictive nomogram were filtered using multivariable logistic regression analysis. The performance of the nomogram was assessed based on the area under the receiver operating characteristic curve (AUC-ROC), calibration plots, and decision curve analysis (DCA).ResultsAfter multivariable logistic regression analysis, certain factors, such as smoking, National Institutes of Health of Stroke Scale (NIHSS) score, blood urea nitrogen-to-creatinine ratio (BUN/Cr), and neutrophil-to-lymphocyte ratio (NLR), were found to be independent predictors of ICH and were used to construct a nomogram. The AUC-ROC values of the nomogram were 0.887 (95% CI: 0.842–0.933) and 0.776 (95% CI: 0.681–0.872) in the training and testing sets, respectively. The AUC-ROC of the nomogram was higher than that of the Multicenter Stroke Survey (MSS), Glucose, Race, Age, Sex, Systolic blood Pressure, and Severity of stroke (GRASPS), and stroke prognostication using age and NIH Stroke Scale-100 positive index (SPAN-100) scores for predicting ICH in both the training and testing sets (p < 0.05). The calibration plot demonstrated good agreement in both the training and testing sets. DCA indicated that the nomogram was clinically useful.ConclusionsThe new nomogram, which included smoking, NIHSS, BUN/Cr, and NLR as variables, had the potential for predicting the risk of ICH in patients with AIS after IVT.

Association of red cell distribution width and D-dimer levels with intracranial hemorrhage in patients with cerebral venous thrombosis

BackgroundPatients with cerebral venous thrombosis (CVT) are at risk of developing intracranial hemorrhage (ICH). Considering the association between ICH and a poor outcome, identifying risk factors for ICH in patients with CVT is of great importance. MethodsIn this observational, retrospective, and double-center research over 3 years at Tongji and Union Hospital, red cell distribution width (RDW) and D-dimer levels were assessed in 117 adult patients with a diagnosis of CVT. Demographics, clinical presentation, imaging evaluation, laboratory results, and outcomes were analyzed. ResultsIn univariate analysis, RDW (odds ratio [OR] 1.30, 95% confidence interval [95% CI] 1.09–1.55, P < 0.001) and D-dimer (OR 1.34, 95% CI 1.13–1.59, P = 0.01) levels were associated with the risk of ICH in patients with CVT. In multivariate analysis, RDW (OR 1.31, 95% CI 1.09–1.58, P < 0.001) and D-dimer (OR 1.33, 95% CI 1.1–1.6, P < 0.001) levels were independently associated with the risk of ICH in patients with CVT after correction for time of onset and white blood cell count. ConclusionElevated RDW and D-dimer levels were associated with an increased risk of ICH in patients with CVT. Further research should be undertaken to investigate their value in predicting CVT-related ICH.

Clinical Relevance of Intracranial Hemorrhage Volume in Primary and Metastatic Brain Tumors

BackgroundVenous thromboembolism occurs in approximately 15-30% of individuals with primary or metastatic brain tumors. Spontaneous intracranial hemorrhage (ICH) is also a frequent complication of brain tumors thus complicating the decision to administer therapeutic anticoagulation. We previously demonstrated that anticoagulation does not increase the risk of ICH in patients with brain metastases; however, in the setting of glioma, the risk of major ICH is 13-fold higher during exposure to anticoagulation. Absent a standardized definition of major intracranial hemorrhage, major was based on bleed volume greater than 10ml, symptoms, or requiring surgical intervention. The aim of this study was to evaluate the 10 mL bleed volume cutoff with clinical presentation and outcomes for ICH with brain tumors.MethodsIn a retrospective matched-cohort study, we evaluated patients who had primary brain tumors (n=133) and those with metastatic tumors (n=293). Matched controls were identified using a round-robin algorithm that identified best-match according to baseline demographics. A blinded review of radiographic imaging was performed and the volume of hemorrhage calculated using the ½ ABC method. Patient charts were reviewed for all surgical procedures associated with hemorrhages as well as for the presence of symptoms such as focal neurologic deficit, headache, nausea, or change in cognitive function. Statistical comparisons were performed by one sided Fisher's test and log rank test on Kaplan-Meier estimates of survival.ResultsA total of 61 out of 133 patients with primary brain tumors (45.8%), and 138 patients out of 293 patients with metastatic tumors (47%) were identified with an intracranial hemorrhage. In metastatic tumors, 87.5% (21 of 24) patients with a bleed volume of 10 mL or higher were symptomatic compared with 36% with smaller volumes (P<0.001). Similarly, glioma patients with a hemorrhage volume of 10 mL or higher was associated with the development of clinical symptoms (83% vs 17%, P<0.001). Enoxaparin administration did not influence the likelihood of symptomatology for hemorrhages > 10 mL either in glioma (P=0.3) or brain metastases (P=0.65). A threshold of 10 mL ICH also discriminated between the need for neurosurgical procedure (odds ratio 8.50, 95% CI 3.29-21.70, P<0.001). The median survival following any hemorrhage was poor (3.2 months) and was not significantly influenced by the size of hemorrhage (P=0.42).ConclusionsIntracranial bleed volume of 10 mL or more in patients with primary or metastatic brain tumors consistently correlated with clinical symptoms and need for surgical intervention. Volume assessment is an important element in assessing the clinical significance of intracranial hemorrhage and this data supports the implementation of a 10 mL volume threshold to characterize intracranial hemorrhages in cancer patients. DisclosuresNeuberg:Synta Pharmaceuticals: Other: Stock shares.

Comparative risk for intracranial hemorrhage related to new oral anticoagulants: A network meta-analysis.

Background:The intracranial hemorrhage (ICH) risk of oral anticoagulants/non-vitamin K antagonist oral anticoagulants (NOACs) remains largely unknown. Patients who need oral anticoagulants such as aspirin or warfarin often suffer from obvious complications.Methods:This network meta-analysis intended to assess the ICH risk in patients taking NOACs. The data from PubMed, the Cochrane database, and Embase were reviewed. All phase III randomized controlled trials of NOACs (apixaban, edoxaban, dabigatran, rivaroxaban), aspirin and warfarin were reviewed.Results:Twenty-three trials involving 137,713 participants were included, involving 6 regimens. Warfarin had the first risk of ICH (surface under the cumulative ranking area: 0.82), followed by dabigatran, edoxaban, aspirin, apixaban, rivaroxaban, and placebo. Dabigatran had the lowest risk of all-cause mortality (surface under the cumulative ranking area: 0.63), followed by apixaban, edoxaban, warfarin, rivaroxaban, aspirin, and placebo.Conclusion:Warfarin significantly increased the risk of ICH in patients taking oral anticoagulants compared with 4 NOACs (dabigatran, edoxaban, apixaban, rivaroxaban) and aspirin. Apixaban is least likely to induce all-cause mortality.

New oral anticoagulants for nonvalvular atrial fibrillation with stable coronary artery disease: A meta-analysis.

New oral anticoagulants (NOACs) are effective and safe in patients with nonvalvular atrial fibrillation (NVAF). Limited evidence is available regarding outcomes for NVAF patients with stable coronary artery disease (CAD). A systematic search of Medline, Embase, and the Cochrane Register was performed. Two reviewers independently performed data extraction and quality assessment using the Cochrane Collaboration risk-of-bias assessment tool. We evaluated all primary publications and secondary analyses comparing NOACs with any other OAC agent for preventing stroke in patients with both NVAF and stable CAD from phase III clinical randomized control trials. The primary outcomes were stroke, systemic embolism (SE), major bleeding, and intracranial hemorrhage (ICH), and the secondary outcomes were cardiovascular (CV) death, all-cause death, and myocardial infarction (MI). Four articles with a total of 19266 patients were included in this study. The pooled results showed a relative risk for stroke/SE with NOACs of 0.83 (95% confidence interval [CI]: 0.71-0.97), for major bleeding 0.85 (95% CI: 0.63-1.14), for ICH 0.36 (95% CI: 0.19-0.54), for MI 1.00 (95% CI: 0.82-1.20), for CV death 0.94 (95% CI: 0.83-1.06), and for all-cause death 0.95 (95% CI: 0.85-1.07). NOACs were effective in preventing stroke/SE and reducing the risk of ICH in patients with both NVAF and CAD.

Incremental Risk of Intracranial Hemorrhage After Mild Traumatic Brain Injury in Patients on Antiplatelet Therapy: Systematic Review and Meta-Analysis.

Mild traumatic brain injury (TBI) is a common event and antiplatelet therapy might represent a risk factor for bleeding. The aim of this study was to evaluate the risk of intracranial hemorrhage (ICH) after mild TBI in patients on antiplatelet therapy through a systematic review and meta-analysis. We conducted a systematic review and meta-analysis of prospective and retrospective observational studies on patients with mild TBI on antiplatelet therapy vs. those not on any antithrombotic therapy. The primary outcome was the risk of ICH in patients with mild TBI based on the first computed tomography scan. Secondary outcome was the risk of mortality and neurosurgery. Nine studies and 14,545 patients were included. The incidence of ICH ranged from 3.6% to 29.4% in the antiplatelet group and from 1.6% to 21.1% in the control group. Patients on antiplatelet therapy had a higher risk of ICH after a mild TBI compared with patients that were not on antithrombotic therapy (risk ratio 1.51; 95% confidence interval 1.21-1.88). No difference was found in the composite outcome of mortality and neurosurgery. Patients on antiplatelet therapy have an increased risk of ICH after mild TBI compared with patients not on antithrombotic therapy. However, the risk is just slightly increased, and the need to perform a computed tomography scan in patients on antiplatelet therapy after a mild TBI should be evaluated case by case, but always considered in patients with other risk factors.

Intravenous Thrombolysis Is Not Associated with Increased Time to Endovascular Treatment

Background: Endovascular treatment (EVT) with or without intravenous thrombolysis (IVT) is effective and safe in is­chemic stroke caused by large vessel occlusion, but IVT might delay time to EVT or increase risk of intracranial hemorrhage (ICH). We assessed the influence of prior IVT on time to treatment and risk of ICH in patients treated with EVT. Methods: We analyzed data from the MR CLEAN Registry and included patients with an anterior circulation occlusion treated with EVT who presented directly to an intervention center, between 2014 and 2017. Primary endpoint was the door to groin time. Secondary outcomes were workflow time intervals and safety outcomes. We compared patients who received EVT only with patients who received IVT prior to EVT. Results: We included 1,427 patients directly referred to an intervention center of whom 1,023 (72%) received IVT + EVT. Adjusted door to CT imaging and door to groin time were shorter in IVT + EVT patients (difference 5.7 min [95% CI: 4.6–6.8] and 7.0 min [95% CI: 2.4–12], respectively) while CT imaging to groin time was similar between the groups. Early recanalization on digital subtraction angiography before EVT was seen more often after prior IVT (11 vs. 5.2%, aOR 2.4 [95% CI: 1.4–4.2]). Rates of symptomatic ICH were similar. Conclusion: Prior IVT did not delay door to groin times and was associated with higher rates of early recanalization, without increasing the risk of ICH. Our results do not warrant withholding IVT prior to EVT.

Bleeding Risk of Low-Molecular Weight Heparin Vs Direct Oral Anticoagulant in Patients with Intracranial Tumors

IntroductionAppropriate anticoagulation management in cancer patients is complicated by the high propensity for recurrent venous thromboembolism (VTE) as well as history of bleeding, altered anatomy, impaired organ function, nutritional issues, and intracranial tumors. The Hokusai trial demonstrated non-inferiority of edoxaban, a direct oral anticoagulant (DOAC), to low-molecular weight heparin (LMWH) in treatment of cancer-associated VTE. In the SELECT D trial, patients with cancer-associated VTE treated with rivaroxaban, another DOAC, had a 4% recurrence of VTE compared to 11% in the group treated with LMWH. These results have challenged the long standing dogma of use of LMWH for the treatment of cancer-associated VTE based on the CLOT trial.One of the particularly challenging features of treating cancer patients with VTE is when patients have known brain tumor(s) as this heightens the concern for intracranial hemorrhage (ICH). A retrospective cohort study reported in Blood in 2015 showed no difference in ICH in patients with intracranial tumors treated with LMWH compared to matched controls not on anticoagulation. This study also confirmed that tumor histology predicts bleeding risk as the metastatic melanoma and renal cell carcinoma patients had greater risk of ICH. The risk of ICH in patients with intracranial tumors treated with DOACs remains unknown.The aim of the present study is to compare the ICH rate in patients with intracranial tumors treated either with a DOAC or LMWH.MethodsWe performed a retrospective analysis of patients with a diagnosis of malignancy with intracranial tumor documented by imaging between May 1, 2011 and December 31, 2016. All patients were on therapeutic anticoagulation with either a DOAC or LMWH. We compared the rate of ICH in patients with intracranial tumors on treatment with DOACs to the rate in those on treatment with LMWH. Additionally, we evaluated the rate of non-intracranial bleeding and recurrent VTE in both groups. CTCAE grading was used for bleeding events. Comparisons among continuous variables were made using t-tests, and comparisons among categorical variables were made using Chi-squared and Fisher's exact tests. Associations were considered significant for P-values (two-sided) ≤ 0.05.ResultsA total of 135 patients, 90 in the LMWH group and 45 in the DOAC group, were available for analysis. For patient demographics and characteristics by treatment group, see Table 1. There was a significant difference between treatment group and type of cancer, with a higher proportion of primary CNS malignancy (versus metastatic disease) in the LMWH group (71.2% vs 42.2%, p=0.003), and a higher proportion of patients in the LMWH group had only 1 brain tumor (55.6% vs 35.6%, p=0.035). There was a significant association between treatment group and whether patients were treated with bevacizumab (p=0.002), with a higher rate of bevacizumab treatment in the LMWH group (28.9% vs. 4.4%).There was not a significant difference between treatment groups and the occurrence of ICH (10.0% LMWH vs. 8.9% DOAC, Table 2). Across treatment groups, the majority of ICH events were grade 1-2, but the LMWH group did have one grade 4 and one grade 5 ICH compared to no high grade ICH in the DOAC group (Table 3). In the LMWH group, nearly all (8/9) of the observed ICH events required anticoagulation to be discontinued. In the DOAC group, only one ICH event required anticoagulant discontinuation, whereas one other ICH event required decreased anticoagulation to prophylactic dosing. In the LMWH group, nearly all (8/9) of the observed ICH events occurred at a time when patients were not on systemic antineoplastic treatment. One ICH event in the LMWH group occurred while the patient was on therapy with a tyrosine kinase inhibitor (TKIs). In the DOAC group, two ICH events occurred at a time when patients were not on systemic antineoplastic treatment, whereas the other two events occurred while the patients were on immunotherapy. There was no significant difference between recurrent clotting events (4.4% LMWH vs. 6.7% DOAC) or other bleeding events (11.1% LMWH vs. 6.7% DOAC).ConclusionIn patients with malignant intracranial tumors, there is no difference in the risk of ICH or other bleeding events between those on therapeutic anticoagulation with a DOAC or LMWH. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Management of venous thromboembolism in patients with glioma

BackgroundVenous thromboembolism (VTE) is a common complication among patients with glioma. However, data on the safety of therapeutic doses of anticoagulation is scarce in this patient population. ObjectivesThe purpose of this study is to evaluate the risk of intracranial hemorrhage (ICH) in glioma patients receiving therapeutic anticoagulation for VTE treatment. Patients and methodsWe conducted a case-control study including glioma patients with and without acute VTE from Jan 2010 to March 2015. Controls were matched based on age, gender and tumor grade. Result569 patients with glioma were identified, 76 (13.3%) developed acute VTE. Of the 70 patients treated with full dose anticoagulant therapy, 14 (20%) patients had a major bleeding including 11 (15.7%) ICH. The odds ratio for ICH in patients with glioma and VTE who were treated with anticoagulation compared to the control group was 7.5 (95% CI, 1.6–34.9) p=0.01. Overall survival was similar for VTE and control group (36 vs. 42months, p=0.93). ConclusionTherapeutic anticoagulation is associated with a 7-fold increase risk of ICH in glioma patients. Data emerging from this study support the need for high quality studies to evaluate the risk of ICH in patients with glioma and VTE.

A meta‐analysis of intracranial hemorrhage in patients with brain tumors receiving therapeutic anticoagulation

Essentials Clinicians may be hesitant to administer anticoagulation in the setting of brain metastases or glioma. In this meta-analysis, we identified nine retrospective cohort studies that met inclusion criteria. Anticoagulation did not increase the risk of intracranial hemorrhage in brain metastasis. In the setting of glioma, anticoagulation resulted in 3.8-fold increase in intracranial hemorrhage. Background Venous thromboembolism commonly occurs in patients with brain tumors. Because of the high rate of spontaneous intracranial hemorrhage (ICH), the safety of therapeutic anticoagulation is commonly questioned. Objective We performed a meta-analysis to evaluate whether therapeutic anticoagulation is associated with an increased risk of intracranial hemorrhage in patients with brain tumors. Patients/Methods A systematic literature search strategy was conducted. Summary statistics for ICH were obtained by calculating the odds ratio using a random effects model and heterogeneity across studies was estimated by the I(2) statistic. Results A total of nine retrospective cohort studies met the criteria for inclusion. The odds ratio (OR) for ICH in patients receiving therapeutic anticoagulation versus those who did not receive anticoagulation was 2.13 (95% confidence interval [CI], 1.00-4.56; I(2) = 46%). In studies evaluating anticoagulation in patients with brain metastases, there was no apparent increased risk of ICH (OR, 1.07; 95% CI, 0.61-1.88; I(2) = 0%). However, in patients with glioma there was an increase in risk of ICH associated with the administration of anticoagulation (OR, 3.75; 95% CI, 1.42-9.95; I(2) = 33%). Conclusions The risk of ICH in patients with brain tumors receiving therapeutic anticoagulation depends on the diagnosis of primary or metastatic brain tumors. Although anticoagulation was not associated with an increased risk of ICH in the setting of brain metastasis, its use resulted in a greater than 3-fold increased risk of ICH in patients with glioma.

Continued Statin Treatment After Acute Intracranial Hemorrhage

Statin therapy has clearly demonstrated a beneficial effect in reducing the risk of first ever and recurrent ischemic stroke in patients with coronary artery and cerebrovascular diseases. However, the overall benefit of statins in patients with previous stroke appears to be partially offset by an increased risk of intracranial hemorrhage (ICH). Post hoc analyses of 2 large randomized trials, Heart Protection Society and Stroke Prevention by Aggressive Reduction in Cholesterol Levels, suggest that patients with previous stroke may be at increased risk of hemorrhagic stroke independently of cholesterol levels.1 Like dynamite, statins help fighting fires (ischemic strokes), but with an added risk of potential collateral damages (ICH). Thus, avoidance of statin initiation or continuation after ICH has been recommended by several experts. In contrast, recent observational cohort studies and 1 meta-analysis found no evidence of increased risk of ICH in patients treated with statins after an ischemic stroke. Therefore, it is a matter of controversy whether continuation or initiation of statins in acute ICH patients with history of ischemic stroke is beneficial or harmful in terms of ICH growth, stroke (ischemic and hemorrhagic) recurrence and clinical outcome. Dr Goldstein, …

Abstract 205: Risk of Intracranial Hemorrhage with Protease-activated Receptor-1 Antagonists

Background: Recent clinical trial data suggest that protease-activated receptor-1 (PAR-1) antagonists may increase the risk of intracranial hemorrhage (ICH). Our objective was to investigate the qualitative and quantitative risk of ICH in patients receiving PAR-1 antagonist therapy. Methods: Pubmed and EMBASE from 1966 to May 2012 were searched to identify relevant studies. We included randomized controlled trials that included a comparison of PAR-1 antagonist with placebo, and in which the total number of patients and ICH events were reported separately for active treatment and control groups. Summary incidence rates, relative risks (RRs), and 95% confidence intervals (CIs) were calculated using random-effects models. Between-study heterogeneity was assessed using the I 2 statistic. Results: In 9 PAR-1 antagonist trials with 42, 000 patients with a history of thrombotic vascular disease or acute coronary syndrome, PAR-1 antagonist treatment was associated with increased risk of ICH (0.59% vs. 0.30%; RR 1.98, 95% CI 1.46 to 2.68, P &lt; 0.00001) (Figure). There was no heterogeneity across trials (P=0.84, I 2 =0%), PAR-1 antagonist agent (P=0.52), treatment duration (P=0.38), or trial-qualifying event (P=0.59). Risk of death from any cause or a cardiovascular cause did not differ between active treatment and control groups. Conclusion: This meta-analysis showed that patients with a history of thrombotic vascular disease or acute coronary syndrome treated with PAR-1 antagonists are at higher risk of experiencing ICH, a dreaded form of stroke, associated with high mortality and greater loss of health over a survivor’s lifetime than ischemic stroke.