Stroke.

Stroke affects up to one in five people during their lifetime in some high-income countries, and up to almost one in two in low-income countries. Globally, it is the second leading cause of death. Clinically, the disease is characterised by sudden neurological deficits. Vascular aetiologies contribute to the most common causes of ischaemic stroke, including large artery disease, cardioembolism, and small vessel disease. Small vessel disease is also the most frequent cause of intracerebral haemorrhage, followed by macrovascular causes. For acute ischaemic stroke, multimodal CT or MRI reveal infarct core, ischaemic penumbra, and site of vascular occlusion. For intracerebral haemorrhage, neuroimaging identifies early radiological markers of haematoma expansion and probable underlying cause. For intravenous thrombolysis in ischaemic stroke, tenecteplase is now a safe and effective alternative to alteplase. In patients with strokes caused by large vessel occlusion, the indications for endovascular thrombectomy have been extended to include larger core infarcts and basilar artery occlusion, and the treatment time window has increased to up to 24 h from stroke onset. Regarding intracerebral haemorrhage, prompt delivery of bundled care consisting of immediate anticoagulation reversal, simultaneous blood pressure lowering, and prespecified stroke unit protocols can improve clinical outcomes. Guided by underlying stroke mechanisms, secondary prevention encompasses pharmacological, vascular, or endovascular interventions and lifestyle modifications.

Trigger factors in patients with a patent foramen ovale-associated stroke: A case-crossover study.

BACKGROUND: Patent foramen ovale (PFO) is a congenital anatomical variant which is associated with strokes in young adults. Contrary to vascular risk factors and atherosclerosis, a PFO is present from birth. However, it is completely unknown how an anatomical structure that is already present at birth in a large proportion of the population can convert into a PFO that causes stroke in a few. Recent studies reported a significant association between certain trigger factors and ischemic stroke in young adults. This study aims to investigate these triggers in PFO-associated stroke. METHODS: The ODYSSEY study, a multicenter prospective cohort study between 2013 and 2021, included patients aged 18-49 years experiencing their first-ever ischemic event. Participants completed a questionnaire about exposure to potential trigger factors. A case-crossover design was used to assess the relative risks (RR) with 95% confidence intervals (95% CI). The primary outcome was the RR of potential trigger factors for PFO-associated stroke. RESULTS: Overall, 1043 patients completed the questionnaire and had an ischemic stroke, of which 124 patients had a PFO-associated stroke (median age 42.1 years, 45.2% men). For patients with PFO-associated stroke, the RR was 26.0 (95% CI 8.0-128.2) for fever, 24.2 (95% CI 8.5-68.7) for flu-like disease, and 3.31 (95% CI 2.2-5.1) for vigorous exercise. CONCLUSION: In conclusion, flu-like disease, fever, and vigorous exercise may convert an asymptomatic PFO into a stroke-causing PFO in young adults. DATA ACCESS STATEMENT: The raw and anonymized data used in this study can be made available to other researchers on request. Written proposals can be addressed to the corresponding author and will be assessed by the ODYSSEY investigators for appropriateness of use, and a data sharing agreement in accordance with Dutch regulations will be put in place before data are shared.

Short-Term and Long-Term Risk of Recurrent Vascular Event by Cause After Ischemic Stroke in Young Adults.

Importance: Cause of ischemic stroke in young people is highly variable; however, the risk of recurrence is often presented with all subtypes of stroke grouped together in classification systems such as the Trial of ORG (danaparoid sodium [Orgaran]) 10172 in Acute Stroke Treatment (TOAST) criteria, which limits the ability to individually inform young patients with stroke about their risk of recurrence. Objective: To determine the short-term and long-term risk of recurrent vascular events after ischemic stroke at a young age by stroke cause and to identify factors associated with recurrence. Design, Setting, and Participants: This cohort study used data from the Observational Dutch Young Symptomatic Stroke Study, a prospective, multicenter, hospital-based cohort study, conducted at 17 hospitals in the Netherlands between 2013 and 2021. Eligible participants included 30-day survivors of an initial, neuroimaging-proven ischemic stroke (aged 18-49 years). Data analysis was conducted from June to July 2023. Exposure: Diagnosis of a first-ever, ischemic stroke via neuroimaging. Main Outcome and Measures: The primary outcome was short-term (within 6 months) and long-term (within 5 years) recurrence risk of any vascular event, defined as fatal or nonfatal recurrent ischemic stroke, transient ischemic attack, myocardial infarction, and revascularization procedure. Predefined characteristics were chosen to identify factors associated with risk of recurrence (cause of stroke, age, sex, stroke severity, and cardiovascular health factors). Results: A total of 1216 patients (median [IQR] age, 44.2 [38.4-47.7] years; 632 male [52.0%]; 584 female [48.0%]) were included, with a median (IQR) follow-up of 4.3 (2.6-6.0) years. The 6-month risk of any recurrent ischemic event was 6.7% (95% CI, 5.3%-8.1%), and the 5-year risk was 12.2% (95% CI, 10.2%-14.2%)The short-term risk was highest for patients with cervical artery dissections (13.2%; 95% CI, 7.6%-18.7%). Other factors associated with a recurrent short-term event were atherothrombotic stroke, rare causes of stroke, and hypertension. The long-term cumulative risk was highest for patients with atherothrombotic stroke (22.7%; 95% CI, 10.6%-34.7%) and lowest for patients with cryptogenic stroke (5.8%; 95% CI, 3.0%-8.5%). Cardioembolic stroke was associated with a recurrent long-term event, as were diabetes and alcohol abuse. Conclusions and Relevance: The findings of this cohort study of 1216 patients with an ischemic stroke at a young age suggest that the risk of recurrent vascular events was high and varied by cause of stroke both for short-term and long-term follow-up, including causes that remained concealed when combined into 1 category in the routinely used TOAST criteria. This knowledge will allow for more personalized counseling of young patients with stroke.

Blood pressure variability and white matter hyperintensities after ischemic stroke.

Background: High blood pressure variability (BPV) may be a risk factor for stroke and dementia in patients with ischemic stroke, but the underlying mechanism is unknown. We aimed to investigate whether high BPV is associated with presence and progression of white matter hyperintensities (WMH). Methods: We performed a post-hoc analysis on the MRI substudy of the PRoFESS trial, including 771 patients with ischemic stroke who underwent MRI at baseline and after a median of 2.1 years. WMH were rated with a semi-quantitative scale. Visit-to-visit BPV was expressed as the coefficient of variation (interval 3-6 months, median number of visits 7). The association of BPV with WMH burden and progression was assessed with linear and logistic regression analyses adjusted for confounders. Results: BPV was associated with burden of periventricular WMH (ß 0.36 95%CI 0.19-0.53, per one SD increase in BPV) and subcortical (log-transformed) WMH (ß 0.25, 95%CI 0.08-0.42). BPV was not associated with periventricular (OR 1.09, 95%CI 0.94-1.27) and subcortical WMH progression (OR 1.15, 95%CI 0.99-1.35). Associations were independent of mean BP. Conclusion: High visit-to-visit BPV was associated with both subcortical and periventricular WMH burden in patients with ischemic stroke, but not with WMH progression in this study.

Long-term Risk of Bleeding and Ischemic Events After Ischemic Stroke or Transient Ischemic Attack in Young Adults.

BACKGROUND AND OBJECTIVES: Guidelines recommend antithrombotic medication as secondary prevention for patients with ischemic stroke or transient ischemic attack (TIA) at young age based on results from trials in older patients. We investigated the long-term risk of bleeding and ischemic events in young patients after ischemic stroke or TIA. METHODS: We included 30-day survivors of first-ever ischemic stroke or TIA aged 18-50 years from the Follow-Up of TIA and Stroke Patients and Unelucidated Risk Factor Evaluation (FUTURE) study, a prospective cohort study of stroke at young age. We obtained information on recurrent ischemia based on structured data collection from 1995 until 2014 as part of the FUTURE study follow-up, complemented with information on any bleeding and ischemic events by retrospective chart review from baseline until last medical consultation or June 2020. Primary outcome was any bleeding; secondary outcome any ischemic event during follow-up. Both were stratified for sex, age, etiology, and use of antithrombotic medication at discharge. Bleeding and ischemic events were classified according to location and bleeding events also by severity. RESULTS: We included 544 patients (56.1% women, median age of 42.2; interquartile range [IQR] 36.5-46.7 years) with a median follow-up of 9.6 (IQR 2.5-14.3) years. Ten-year cumulative risk of any bleeding event was 21.8% (95% CI 17.4-26.0) and 33.9% (95% CI 28.3-37.5) of any ischemic event. Risk of bleeding was higher in women with a cumulative risk of 28.2% (95% CI 21.6-34.3) vs 13.7% (95% CI 8.2-18.9) in men (p < 0.01), mainly because of gynecologic bleeds. Female sex (p < 0.001) and age between 40 and 49 years (p = 0.04) were independent predictors of bleeding. DISCUSSION: Young patients after ischemic stroke or TIA have a substantial long-term risk of both bleeding (especially women) and ischemic events. Future studies should investigate the effects of long-term antithrombotics in young patients, taking into account the risk of bleeding complications.

Balancing Benefits and Risks of Long-Term Antiplatelet Therapy in Noncardioembolic Transient Ischemic Attack or Stroke.

Background and Purpose: Lifelong treatment with antiplatelet drugs is recommended following a transient ischemic attack or ischemic stroke. Bleeding complications may offset the benefit of antiplatelet drugs in patients at increased risk of bleeding and low risk of recurrent ischemic events. We aimed to investigate the net benefit of antiplatelet treatment according to an individuals' bleeding risk. Methods: We pooled individual patient data from 6 randomized clinical trials (CAPRIE [Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events], ESPS-2 [European Stroke Prevention Study-2], MATCH [Management of Atherothrombosis With Clopidogrel in High-Risk Patients], CHARISMA [Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance], ESPRIT [European/Australasian Stroke Prevention in Reversible Ischemia Trial], and PRoFESS [Prevention Regimen for Effectively Avoiding Second Strokes]) investigating antiplatelet therapy in the subacute or chronic phase after noncardioembolic transient ischemic attack or stroke. Patients were stratified into quintiles according to their predicted risk of major bleeding with the S2TOP-BLEED score. The annual risk of major bleeding and recurrent ischemic events was assessed per quintile for 4 scenarios: (1) aspirin monotherapy, (2) aspirin-clopidogrel versus aspirin or clopidogrel monotherapy, (3) aspirin-dipyridamole versus clopidogrel, and (4) aspirin versus clopidogrel. Net benefit was calculated for the second, third, and fourth scenario. Results: Thirty seven thousand eighty-seven patients were included in the analyses. Both risk of major bleeding and recurrent ischemic events increased over quintiles of predicted bleeding risk, but risk of ischemic events was consistently higher (eg, from 0.7%/y (bottom quintile) to 3.2%/y (top quintile) for major bleeding on aspirin and from 2.5%/y to 10.2%/y for risk of ischemic events on aspirin). Treatment with aspirin-clopidogrel led to more major bleedings (0.9%­1.7% per year), than reduction in ischemic events (ranging from 0.4% to 0.9/1.0% per year) across all quintiles. There was no clear preference for either aspirin-dipyridamole or clopidogrel according to baseline bleeding risk. Conclusions: Among patients with a transient ischemic attack or ischemic stroke included in clinical trials of antiplatelet therapy, the risk of recurrent ischemic events and of major bleeding increase in parallel. Antiplatelet treatment cannot be individualized solely based on bleeding risk assessment.

Blood pressure, blood pressure variability and the risk of poststroke dementia.

OBJECTIVE: High blood pressure and blood pressure variability are potential, modifiable risk factors of poststroke dementia. We aimed to investigate the association between achieved blood pressure, blood pressure variability and poststroke dementia. METHODS: We studied 17 064 patients with noncardioembolic ischemic stroke included in the Prevention Regimen for Effectively avoiding Second Strokes (PRoFESS) trial. We analysed the data as a single observational cohort. We studied mean achieved SBP and DBP and blood pressure variability defined as coefficient of variation (SD/mean∗100). The association between blood pressure and dementia was investigated with logistic regression analysis, correcting for sociodemographic factors and cardiovascular risk factors. RESULTS: During 39 818 person-years of follow-up, 817 patients were diagnosed with dementia (2.1 per 100 person-years). We found a significant nonlinear association between mean SBP and the risk of dementia, implying a U-shaped association between mean SBP and dementia. Mean SBP of 120-129 mmHg was associated with a significantly higher risk of dementia than 130-139 mmHg [odds ratio (OR) 1.28; 95% confidence interval (95% CI) 1.03-1.58]. There was no indication of a U-shaped association between mean DBP and dementia, and no significant association between mean DBP categories and dementia. Higher blood pressure variability was associated with an increased risk of dementia (OR 1.06 per point increase, 95% CI 1.02-1.04), independent of mean SBP. CONCLUSION: Among patients with a recent noncardioembolic ischemic stroke, there appears to be a U-shaped association between achieved SBP and dementia. High blood pressure variability is associated with an increased risk of poststroke dementia.

[Revised guideline 'Brain metastases': More treatment options]. / Herziene richtlijn 'Hersenmetastasen'.

The guideline on brain metastasis from the Netherlands Society of Neurology has been updated. Important changes have been made, particularly with regard to treatment of brain metastases. Treatment of patients with brain metastases is complex and requires a multidisciplinary approach to formulate an optimal, individualized treatment plan. Neurosurgical resection may also be considered in patients with multiple brain metastases and one dominant, symptomatic lesion, if the patient is in good clinical condition. Stereotactic radiosurgery is a treatment option for patients with a maximum of 10 brain metastases, depending on the size and number of metastases. The indication for whole brain radiotherapy is relatively limited. Doctors should be cautious with whole brain radiotherapy in patients with a Karnofsky Performance Status <70. In patients with small, asymptomatic brain metastases, targeted therapy or immune therapy may be considered without locoregional therapy.

Refining prediction of major bleeding on antiplatelet treatment after transient ischaemic attack or ischaemic stroke.

INTRODUCTION: Bleeding is the main safety concern of treatment with antiplatelet drugs. We aimed to refine prediction of major bleeding on antiplatelet treatment after a transient ischaemic attack (TIA) or stroke by assessing the added value of new predictors to the existing S2TOP-BLEED score. PATIENTS AND METHODS: We used Cox regression analysis to study the association between candidate predictors and major bleeding among 2072 patients with a transient ischaemic attack or ischaemic stroke included in a population-based study (Oxford Vascular Study - OXVASC). An updated model was proposed and validated in 1094 patients with a myocardial infarction included in OXVASC. Models were compared with c-statistics, calibration plots, and net reclassification improvement. RESULTS: Independent predictors for major bleeding on top of S2TOP-BLEED variables were peptic ulcer (hazard ratio (HR): 1.72; 1.04-2.86), cancer (HR: 2.40; 1.57-3.68), anaemia (HR: 1.55; 0.99-2.44) and renal failure (HR: 2.20; 1.57-4.28). Addition of those variables improved discrimination from 0.69 (0.64-0.73) to 0.73 (0.69-0.78) in the TIA/stroke cohort (p = 0.01). Performance improved particularly for upper gastro-intestinal bleeds (0.70; 0.64-0.75 to 0.77; 0.72-0.82). Net reclassification improved over the entire range of the score (net reclassification improvement: 0.56; 0.36-0.76). In the validation cohort, discriminatory performance improved from 0.68 (0.62-0.74) to 0.70 (0.64-0.76). DISCUSSION AND CONCLUSION: Peptic ulcer, cancer, anaemia and renal failure improve predictive performance of the S2TOP-BLEED score for major bleeding after stroke. Future external validation studies will be required to confirm the value of the STOP-BLEED+ score in transient ischaemic attack/stroke patients.

Development and internal validation of a prediction rule for post-stroke infection and post-stroke pneumonia in acute stroke patients.

INTRODUCTION: Patients with acute stroke are at high risk for infection. These infections are associated with unfavourable outcome after stroke. A prediction rule can identify the patients at the highest risk for strategies to prevent infection. We aim to develop a prediction rule for post-stroke pneumonia and other infections in patients with acute stroke. PATIENTS AND METHODS: We used data from the Preventive Antibiotics in Stroke Study, a multicentre randomised trial comparing preventive ceftriaxone vs. standard stroke care in patients with acute stroke. Possible predictors for post-stroke pneumonia or infection were selected from the literature. Backward elimination logistic regression analysis was used to construct prediction rules for pneumonia or infection. Internal validation was performed and a risk chart was constructed. We adjusted for preventive antibiotic use. RESULTS: Pneumonia was diagnosed in 159 of the 2538 included patients, and infection in 348. Pneumonia was predicted by higher age, male sex, pre-stroke disability, medical history of chronic obstructive pulmonary disease, more severe stroke, dysphagia and intracerebral haemorrhage (rather than ischaemic stroke). Infections were predicted by higher age, male sex, history of diabetes, chronic obstructive pulmonary disease, more severe stroke, dysphagia, use of bladder catheter, preventive antibiotic use and intracerebral haemorrhage. With the prediction rule developed, risks for pneumonia ranged from 0.4% to 56.2% and from 1.8% to 88.0% for infection. Discrimination of the score was good (C-statistic, 0.84; 95% CI: 0.81-0.87 and 0.82; 95% CI: 0.79-0.84 for pneumonia and infection). CONCLUSIONS: The Preventive Antibiotics in Stroke Study pneumonia and infection rule identify patients at the highest risk for post-stroke pneumonia or infection and may be used for future studies and novel therapies, after confirmation in an external population.

External Validation of Risk Scores for Major Bleeding in a Population-Based Cohort of Transient Ischemic Attack and Ischemic Stroke Patients.

BACKGROUND AND PURPOSE: The S2TOP-BLEED score may help to identify patients at high risk of bleeding on antiplatelet drugs after a transient ischemic attack or ischemic stroke. The score was derived on trial populations, and its performance in a real-world setting is unknown. We aimed to externally validate the S2TOP-BLEED score for major bleeding in a population-based cohort and to compare its performance with other risk scores for bleeding. METHODS: We studied risk of bleeding in 2072 patients with a transient ischemic attack or ischemic stroke on antiplatelet agents in the population-based OXVASC (Oxford Vascular Study) according to 3 scores: S2TOP-BLEED, REACH, and Intracranial-B2LEED3S. Performance was assessed with C statistics and calibration plots. RESULTS: During 8302 patient-years of follow-up, 117 patients had a major bleed. The S2TOP-BLEED score showed a C statistic of 0.69 (95% confidence interval [CI], 0.64-0.73) and accurate calibration for 3-year risk of major bleeding. The S2TOP-BLEED score was much more predictive of fatal bleeding than nonmajor bleeding (C statistics 0.77; 95% CI, 0.69-0.85 and 0.50; 95% CI, 0.44-0.58). The REACH score had a C statistic of 0.63 (95% CI, 0.58-0.69) for major bleeding and the Intracranial-B2LEED3S score a C statistic of 0.60 (95% CI, 0.51-0.70) for intracranial bleeding. The ratio of ischemic events versus bleeds decreased across risk groups of bleeding from 6.6:1 in the low-risk group to 1.8:1 in the high-risk group. CONCLUSIONS: The S2TOP-BLEED score shows modest performance in a population-based cohort of patients with a transient ischemic attack or ischemic stroke. Although bleeding risks were associated with risks of ischemic events, risk stratification may still be useful to identify a subgroup of patients at particularly high risk of bleeding, in whom preventive measures are indicated.

Predicting the presence of macrovascular causes in non-traumatic intracerebral haemorrhage: the DIAGRAM prediction score.

OBJECTIVE: A substantial part of non-traumatic intracerebral haemorrhages (ICH) arises from a macrovascular cause, but there is little guidance on selection of patients for additional diagnostic work-up. We aimed to develop and externally validate a model for predicting the probability of a macrovascular cause in patients with non-traumatic ICH. METHODS: The DIagnostic AngioGRAphy to find vascular Malformations (DIAGRAM) study (n=298; 69 macrovascular cause; 23%) is a prospective, multicentre study assessing yield and accuracy of CT angiography (CTA), MRI/ magnetic resonance angiography (MRA) and intra-arterial catheter angiography in diagnosing macrovascular causes in patients with non-traumatic ICH. We considered prespecified patient and ICH characteristics in multivariable logistic regression analyses as predictors for a macrovascular cause. We combined independent predictors in a model, which we validated in an external cohort of 173 patients with ICH (78 macrovascular cause, 45%). RESULTS: Independent predictors were younger age, lobar or posterior fossa (vs deep) location of ICH, and absence of small vessel disease (SVD). A model that combined these predictors showed good performance in the development data (c-statistic 0.83; 95% CI 0.78 to 0.88) and moderate performance in external validation (c-statistic 0.66; 95% CI 0.58 to 0.74). When CTA results were added, the c-statistic was excellent (0.91; 95% CI 0.88 to 0.94) and good after external validation (0.88; 95% CI 0.83 to 0.94). Predicted probabilities varied from 1% in patients aged 51-70 years with deep ICH and SVD, to more than 50% in patients aged 18-50 years with lobar or posterior fossa ICH without SVD. CONCLUSION: The DIAGRAM scores help to predict the probability of a macrovascular cause in patients with non-traumatic ICH based on age, ICH location, SVD and CTA.

Early time course of major bleeding on antiplatelet therapy after TIA or ischemic stroke.

OBJECTIVE: To study the early time course of major bleeding and its subtypes in patients with cerebral ischemia on dual and single antiplatelet therapy. METHODS: We performed a post hoc analysis on individual patient data from 6 randomized clinical trials (Clopidogrel Versus Aspirin in Patients at Risk of Ischaemic Events [CAPRIE], Second European Stroke Prevention Study [ESPS-2], Management of Atherothrombosis With Clopidogrel in High-Risk Patients [MATCH], Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance [CHARISMA], European/Australasian Stroke Prevention in Reversible Ischaemia Trial [ESPRIT], and Prevention Regimen for Effectively Avoiding Second Strokes [PRoFESS]) including 45,195 patients with a TIA or noncardioembolic ischemic stroke. We studied incidence rates of bleeding per antiplatelet regimen stratified by time from randomization (≤30, 31-90, 91-180, 181-365, >365 days). We calculated incidence rates per trial and pooled estimates with random-effects meta-analysis. We performed Poisson regression to assess differences between time periods with adjustment for age and sex. RESULTS: The incidence of major bleeding on aspirin plus clopidogrel and aspirin plus -dipyridamole was highest in the first 30 days, 5.8 and 4.9 per 100 person-years, respectively, and was significantly higher than at 31 to 90 days (rate ratio 1.98, 95% confidence interval 1.16-3.40 for aspirin plus clopidogrel; rate ratio 1.94, 95% confidence interval 1.24-3.03 for aspirin plus dipyridamole). Incidence rates on aspirin and clopidogrel monotherapy were 2.8 and 2.5 per 100 person-years, respectively, in the first 30 days, with no significant change over time. The time course was similar for gastrointestinal bleeds. There was no early excess of intracranial hemorrhage in patients on either dual or single antiplatelet therapy. CONCLUSION: Dual antiplatelet therapy is associated with high early risks of major and gastrointestinal bleeding that decline after the first month in trial cohorts.

Predicting Major Bleeding in Ischemic Stroke Patients With Atrial Fibrillation.

BACKGROUND AND PURPOSE: Performance of risk scores for major bleeding in patients with atrial fibrillation and a previous transient ischemic attack or ischemic stroke is not well established. We aimed to validate risk scores for major bleeding in patients with atrial fibrillation treated with oral anticoagulants after cerebral ischemia and explore the net benefit of oral anticoagulants among bleeding risk categories. METHODS: We analyzed 3623 patients with a history of transient ischemic attack or stroke included in the RE-LY trial (Randomized Evaluation of Long-Term Anticoagulation Therapy). We assessed performance of HEMORR2HAGES (hepatic or renal disease, ethanol abuse, malignancy, older age, reduced platelet count or function, hypertension [uncontrolled], anemia, genetic factors, excessive fall risk, and stroke), Shireman, HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly), ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation), and ORBIT scores (older age, reduced haemoglobin/haematocrit/history of anaemia, bleeding history, insufficient kidney function, and treatment with antiplatelet) with C statistics and calibration plots. Net benefit of oral anticoagulants was explored by comparing risk reduction in ischemic stroke with risk increase in major bleedings on warfarin. RESULTS: During 6922 person-years of follow-up, 266 patients experienced a major bleed (3.8 per 100 person-years). C statistics ranged from 0.62 (Shireman) to 0.67 (ATRIA). Calibration was poor for ATRIA and moderate for other models. The reduction in recurrent ischemic strokes on warfarin was larger than the increase in major bleeding risk, irrespective of bleeding risk category. CONCLUSIONS: Performance of prediction models for major bleeding in patients with cerebral ischemia and atrial fibrillation is modest but comparable with performance in patients with only atrial fibrillation. Bleeding risk scores cannot guide treatment decisions for oral anticoagulants but may still be useful to identify modifiable risk factors for bleeding. Clinical usefulness may be best for ORBIT, which is based on a limited number of easily obtainable variables and showed reasonable performance.

Predicting major bleeding in patients with noncardioembolic stroke on antiplatelets: S2TOP-BLEED.

OBJECTIVE: To develop and externally validate a prediction model for major bleeding in patients with a TIA or ischemic stroke on antiplatelet agents. METHODS: We combined individual patient data from 6 randomized clinical trials (CAPRIE, ESPS-2, MATCH, CHARISMA, ESPRIT, and PRoFESS) investigating antiplatelet therapy after TIA or ischemic stroke. Cox regression analyses stratified by trial were performed to study the association between predictors and major bleeding. A risk prediction model was derived and validated in the PERFORM trial. Performance was assessed with the c statistic and calibration plots. RESULTS: Major bleeding occurred in 1,530 of the 43,112 patients during 94,833 person-years of follow-up. The observed 3-year risk of major bleeding was 4.6% (95% confidence interval [CI] 4.4%-4.9%). Predictors were male sex, smoking, type of antiplatelet agents (aspirin-clopidogrel), outcome on modified Rankin Scale ≥3, prior stroke, high blood pressure, lower body mass index, elderly, Asian ethnicity, and diabetes (S2TOP-BLEED). The S2TOP-BLEED score had a c statistic of 0.63 (95% CI 0.60-0.64) and showed good calibration in the development data. Major bleeding risk ranged from 2% in patients aged 45-54 years without additional risk factors to more than 10% in patients aged 75-84 years with multiple risk factors. In external validation, the model had a c statistic of 0.61 (95% CI 0.59-0.63) and slightly underestimated major bleeding risk. CONCLUSIONS: The S2TOP-BLEED score can be used to estimate 3-year major bleeding risk in patients with a TIA or ischemic stroke who use antiplatelet agents, based on readily available characteristics. The discriminatory performance may be improved by identifying stronger predictors of major bleeding.

Blood pressure levels and the risk of intracerebral hemorrhage after ischemic stroke.

OBJECTIVE: To investigate the association between blood pressure (BP) levels and risk of intracerebral hemorrhage (ICH) after ischemic stroke. METHODS: We performed a post hoc analysis of data from the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial, a randomized clinical trial including 20,332 patients with recent noncardioembolic ischemic stroke. BP measurements were divided into predefined categories. We calculated incidence rates per BP category and performed multivariable Cox regression analysis with systolic blood pressure (SBP) and diastolic blood pressure (DBP) categories as time-dependent covariables. RESULTS: One hundred thirty-three ICHs occurred during 50,778 person-years of follow-up, resulting in an incidence rate of 2.6 per 1,000 person-years. The incidence rate of ICH increased with increasing SBP and DBP categories. Risk of ICH was significantly higher in patients with SBP ≥160 mm Hg (hazard ratio 2.27, 95% confidence interval 1.34-3.86) compared with those with SBP of 130-<140 mm Hg and in patients with DBP ≥100 mm Hg (hazard ratio 3.08, 95% confidence interval 1.78-5.34) compared with those with DBP of 80-<90 mm Hg. The association between SBP or DBP and ICH did not differ by ischemic stroke subtype (p = 0.55 and 0.93). CONCLUSIONS: Among patients with recent noncardioembolic ischemic stroke, the risk of ICH is high. High SBP and DBP are associated with an increased risk of ICH. The association between BP and ICH is not dependent on ischemic stroke subtype.

Yield of angiographic examinations in isolated intraventricular hemorrhage: A case series and systematic review of the literature.

BACKGROUND: It is unknown which patients with non-traumatic isolated intraventricular hemorrhage should undergo angiographic imaging to detect an underlying macrovascular cause and which modality has the highest yield. We studied yield of angiographic examinations in patients with isolated intraventricular hemorrhage. METHODS: We reviewed medical records of patients with intraventricular hemorrhage admitted to the University Medical Center Utrecht between 2002 and 2012. We searched PubMed and Embase for studies on angiographic examinations in intraventricular hemorrhage until January 2014. We calculated yield of angiographic imaging and investigated influence of age, hypertension and anticoagulant use with meta-regression analysis. RESULTS: We identified 39 patients of whom 30 underwent an angiographic study. CTA suggested a macrovascular abnormality in nine patients, which was confirmed by DSA in seven. In the literature, we found 16 studies describing 209 patients. Pooled analysis showed a yield of 58% for DSA (95% CI 48-68%; 147 patients). One small study described the yield of CTA or MRA (0%; 4 patients). Yield of angiographic imaging decreased with increasing age (-2.6%; -5.0 to -0.2 per year increase) but was not affected by history of hypertension (-8.3%; -80.8 to 64.2) or anticoagulant use (-47.1%; -110.3 to 16.1). CONCLUSION: The reported yield of DSA in isolated intraventricular hemorrhage is around 50% but varies considerably, probably due to differences in clinical judgment on the need for angiography performance. The yield is higher in younger patients but based on the available data, it is not possible to set age or other criteria for patients in whom DSA can be safely omitted.