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Browsing by Author "Arima, Hisatomi"

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Applicability of ENCHANTED trial results to current acute ischemic stroke patients eligible for intravenous thrombolysis in England and Wales: Comparison with the Sentinel Stroke National Audit Programme registry
(Sage Publishing, 2019-10) Robinson, Thompson; Bray, Benjamin; Paley, Lizz; Sprigg, Nikola; Wan, Xia; Arima, Hisatomi; Bath, Philip; Broderick, Joseph; Durham, Alice; Kim, Jong; Lavados, Pablo; Lee, Tsong-Hai; Martins, Sheila; Nguyen, Thang; Pandian, Jeyaraj; Parsons, Mark; Pontes-Neto, Octavio; Ricci, Stefano; Sharma, Vijay; Wang, Jiguang; Woodward, Mark; Rudd, Anthony; Chalmers, John; Anderson, Craig; ENCHANTED Investigators
Background: Randomized controlled trials provide high-level evidence, but the necessity to include selected patients may limit the generalisability of their results. Methods: Comparisons were made of baseline and outcome data between patients with acute ischemic stroke (AIS) recruited into the alteplase-dose arm of the international, multi-center, Enhanced Control of Hypertension and Thrombolysis Stroke study (ENCHANTED) in the United Kingdom (UK), and alteplase-treated AIS patients registered in the UK Sentinel Stroke National Audit Programme (SSNAP) registry, over the study period June 2012 to October 2015. Results: There were 770 AIS patients (41.2% female; mean age 72 years) included in ENCHANTED at sites in England and Wales, which was 19.5% of alteplase-treated AIS patients registered in the SSNAP registry. Trial participants were significantly older, had lower baseline neurological severity, less likely Asian, and had more premorbid symptoms, hypertension and atrial fibrillation. Although ENCHANTED participants had higher rates of symptomatic intracerebral hemorrhage than those in SSNAP, there were no differences in onset-to-treatment time, levels of disability (assessed by the modified Rankin scale) at hospital discharge, and mortality over 90 days between groups. Conclusions: Despite the high level of participation, equipoise over the dose of alteplase among UK clinician investigators favored the inclusion of older, frailer, milder AIS patients in the ENCHANTED trial.
Associations of Early Systolic Blood Pressure Control and Outcome After Thrombolysis- Eligible Acute Ischemic Stroke: Results From the ENCHANTED Study
(2022) Wang, Xia; Minhas, Jatinder S.; Moullaali, Tom J.; Di Tanna, Gian Luca; Lindley, Richard I.; Chen, Xiaoying; Arima, Hisatomi; Chen, Guofang; Delcourt, Candice; Bath, Philip M.; Broderick, Joseph P.; Demchuk, Andrew M.; Donnan, Geoffrey A.; Durham, Alice C.; Lavados, Pablo; Lee, Tsong-Hai; Levi, Christopher; Martins, Sheila O.; Olavarría, Verónica V.; Pandian, Jeyaraj D.; Parsons, Mark W.; Pontes-Neto, Octavio M.; Ricci, Stefano; Sato, Shoichiro; Sharma, Vijay K.; Silva, Federico; Thang, Nguyen H.; Wang, Ji-Guang; Woodward, Mark; Chalmers, John; Song, Lili; Anderson, Craig S.; Robinson, Thompson G.
BACKGROUND AND PURPOSE: In thrombolysis-eligible patients with acute ischemic stroke, there is uncertainty over the most appropriate systolic blood pressure (SBP) lowering profile that provides an optimal balance of potential benefit (functional recovery) and harm (intracranial hemorrhage). We aimed to determine relationships of SBP parameters and outcomes in thrombolyzed acute ischemic stroke patients. METHODS: Post hoc analyzes of the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study), a partial-factorial trial of thrombolysis-eligible and treated acute ischemic stroke patients with high SBP (150–180 mm Hg) assigned to low-dose (0.6 mg/kg) or standard-dose (0.9 mg/kg) alteplase and intensive (target SBP, 130–140 mm Hg) or guideline-recommended (target SBP <180 mm Hg) treatment. All patients were followed up for functional status and serious adverse events to 90 days. Logistic regression models were used to analyze 3 SBP summary measures postrandomization: attained (mean), variability (SD) in 1–24 hours, and magnitude of reduction in 1 hour. The primary outcome was a favorable shift on the modified Rankin Scale. The key safety outcome was any intracranial hemorrhage. RESULTS: Among 4511 included participants (mean age 67 years, 38% female, 65% Asian) lower attained SBP and smaller SBP variability were associated with favorable shift on the modified Rankin Scale (per 10 mm Hg increase: odds ratio, 0.76 [95% CI, 0.71–0.82]; P<0.001 and 0.86 [95% CI, 0.76–0.98]; P=0.025) respectively, but not for magnitude of SBP reduction (0.98, [0.93– 1.04]; P=0.564). Odds of intracranial hemorrhage was associated with higher attained SBP and greater SBP variability (1.18 [1.06–1.31]; P=0.002 and 1.34 [1.11–1.62]; P=0.002) but not with magnitude of SBP reduction (1.05 [0.98–1.14]; P=0.184). CONCLUSIONS: Attaining early and consistent low levels in SBP <140 mm Hg, even as low as 110 to 120 mm Hg, over 24 hours is associated with better outcomes in thrombolyzed acute ischemic stroke patients.
Associations with health-related quality of life after intracerebral haemorrhage: pooled analysis of INTERACT studies
(BMJ Publishing Group, 2017) Delcourt, Candice; Zheng, Danni; Chen, Xiaoying; Hackett, Maree; Arima, Hisatomi; Hata, Jun; Heeley, Emma; Al-Shahi Salman, Rustam; Woodward, Mark; Huang, Yining; Robinson, Thompson; Lavados, Pablo; Lindley, Richard I; Stapf, Christian; Davies, Leo; Chalmers, John; Anderson, Craig; Sato, Shoichiro; INTERACT Investigators
BACKGROUND AND PURPOSE: Limited data exist on health-related quality of life (HRQoL) after intracerebral haemorrhage (ICH). We aimed to determine baseline factors associated with HRQoL among participants of the pilot and main phases of the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trials (INTERACT 1 and 2). METHODS: The INTERACT studies were randomised controlled trials of early intensive blood pressure (BP) lowering in patients with ICH (<6 hours) and elevated systolic BP (150-220 mm Hg). HRQoL was determined using the European Quality of Life Scale (EQ-5D) at 90 days, completed by patients or proxy responders. Binary logistic regression analyses were performed to identify factors associated with poor overall HRQoL. RESULTS: 2756 patients were included. Demographic, clinical and radiological factors associated with lower EQ-5D utility score were age, randomisation outside of China, antithrombotic use, high baseline National Institutes of Health Stroke Scale (NIHSS) score, larger ICH, presence of intraventricular extension and use of proxy responders. High (≥14) NIHSS score, larger ICH and proxy responders were associated with low scores in all five dimensions of the EQ-5D. The NIHSS score had a strong association with poor HRQoL (p<0.001). Female gender and antithrombotic use were associated with decreased scores in dimensions of pain/discomfort and usual activity, respectively. CONCLUSIONS: Poor HRQoL was associated with age, comorbidities, proxy source of assessment, clinical severity and ICH characteristics. The strongest association was with initial clinical severity defined by high NIHSS score.
Blood pressure variability and outcome after acute intracerebral haemorrhage: a post-hoc analysis of INTERACT2, a randomised controlled trial
(Elsevier, 2014) Manning, Lisa; Hirakawa, Yoichiro; Arima, Hisatomi; Wang, Xia; Chalmers, John; Wang, Jiguang; Lindley, Richard; Heeley, Emma; Delcourt, Candice; Neal, Bruce; Lavados, Pablo; Davis, Stephen; Tzourio, Christophe; Huang, Yining; Stapf, Christian; Woodward, Mark; Rothwell, Peter; Robinson, Thompson; Anderson, Craig
Background: High blood pressure is a prognostic factor for acute stroke, but blood pressure variability might also independently predict outcome. We assessed the prognostic value of blood pressure variability in participants of INTERACT2, an open-label randomised controlled trial (ClinicalTrials.gov number NCT00716079). Methods: INTERACT2 enrolled 2839 adults with spontaneous intracerebral haemorrhage (ICH) and high systolic blood pressure (150–220 mm Hg) without a definite indication or contraindication to early intensive treatment to reduce blood pressure. Participants were randomly assigned to intensive treatment (target systolic blood pressure <140 mm Hg within 1 h using locally available intravenous drugs) or guideline-recommended treatment (target systolic blood pressure <180 mm Hg) within 6 h of onset of ICH. The primary outcome was death or major disability at 90 days (modified Rankin Scale score ≥3) and the secondary outcome was an ordinal shift in modified Rankin Scale scores at 90 days, assessed by investigators masked to treatment allocation. Blood pressure variability was defined according to standard criteria: five measurements were taken in the first 24 h (hyperacute phase) and 12 over days 2–7 (acute phase). We estimated associations between blood pressure variability and outcomes with logistic and proportional odds regression models. The key parameter for blood pressure variability was standard deviation (SD) of systolic blood pressure, categorised into quintiles. Findings: We studied 2645 (93·2%) participants in the hyperacute phase and 2347 (82·7%) in the acute phase. In both treatment cohorts combined, SD of systolic blood pressure had a significant linear association with the primary outcome for both the hyperacute phase (highest quintile adjusted OR 1·41, 95% CI 1·05–1·90; ptrend=0·0167) and the acute phase (highest quintile adjusted OR 1·57, 95% CI 1·14–2·17; ptrend=0·0124). The strongest predictors of outcome were maximum systolic blood pressure in the hyperacute phase and SD of systolic blood pressure in the acute phase. Associations were similar for the secondary outcome (for the hyperacute phase, highest quintile adjusted OR 1·43, 95% CI 1·14–1·80; ptrend=0·0014; for the acute phase OR 1·46, 95% CI 1·13–1·88; ptrend=0·0044). Interpretation: Systolic blood pressure variability seems to predict a poor outcome in patients with acute intracerebral haemorrhage. The benefits of early treatment to reduce systolic blood pressure to 140 mm Hg might be enhanced by smooth and sustained control, and particularly by avoiding peaks in systolic blood pressure. Funding: National Health and Medical Research Council of Australia.
Blood pressure variability and outcome in acute ischemic and hemorrhagic stroke: a post hoc analysis of the HeadPoST study
(2019) Minhas, Jatinder; Wang, Xia; Lavados, Pablo; Moullaali, Tom; Arima, Hisatomi; Billot, Laurent; Olavarria, Veronica; Middleton, Sandy; Pontes, Octavio; De Silva, H Asita; Lee, Tsong; Pandian, Jeyaraj; Mead, Gillian; Watkins, Caroline; Chalmers, John; Anderson, Craig S; Robinson, Thompson; HeadPoST Investigators
The Head Positioning in Acute Stroke Trial (HeadPoST) is a pragmatic, international, cluster crossover randomized trial of 11,093 patients with acute stroke assigned to a lying-flat (0°) or sitting-up (head elevated ≥30°) position. This post hoc analysis aimed to determine the association between blood pressure variability (BPV) and outcomes for patients from a wide range of international clinical settings and how the association was modified by randomized head position. BPV was defined according to the standard criteria, with the key parameter considered the coefficient of variation (CV) of systolic BP (SBP) over 24 h. Outcome was ordinal 90-day Modified Rankin Scale (mRS) score. The association was analyzed by ordinal, logistic regression, hierarchical, mixed models with fixed intervention (lying flat vs. sitting up), and fixed period, random cluster, and random cluster-period, effects. Nine thousand one hundred and fifty six (8324 acute ischemic stroke and 817 intracerebral hemorrhage; mean age 68.1 years; 39.2% women) were included in the analysis. CV of SBP had a significant linear association with unfavorable shift of mRS at 90 days (adjusted odds ratio 1.06, 95% confidence interval 1.02-1.11; P = 0.01). There was no heterogeneity of the association by randomized head positioning. In addition, CV of diastolic BP (DBP) (1.08, 1.03-1.12; P = 0.001) over 24 h post stroke was significantly associated with 3-month poor outcome. The association was more apparent in sitting-up position (1.12, 1.06-1.19) compared with lying-flat position (1.03, 0.98-1.09) (P interaction = 0.005). BPV was associated with adverse stroke outcome, and the magnitude of the association was greater with sitting-up head positioning in terms of DBP variability.
Characteristics, management and response to alteplase in China versus non-China participants of the ENCHANTED trial
(2017) Song, Lily; Wang, Xia; Robinson, Thompson; Lindley, Richard I; Arima, Hisatomi; Lavados, Pablo; Chen, Xiaoying; Chalmers, John; Anderson, Craig S
Background: The characteristics of patients with acute ischaemic stroke (AIS) and their management vary across regions, which may influence outcomes. We examined for differential patterns of outcome between China and non-China participants of the ENhanced Control of Hypertension And Thrombolysis strokE stuDy (ENCHANTED), which tested different alteplase doses in AIS. Methods: ENCHANTED was an international, multicentre, open, blinded-endpoint trial of the effects of low-dose (0.6 mg/kg) versus standard-dose (0.9 mg/kg) intravenous alteplase on 90-day disability outcomes and symptomatic intracerebral haemorrhage (sICH) in 3310 patients with AIS. Results: Participants (n=1419, 48%) in China were younger, and more often male, hypertensive and with prior stroke and coronary artery disease, but less likely to have atrial fibrillation and use antihypertensive, antithrombotic and lipid-lowering agents, compared with non-China patients with AIS. Although China participants had more AIS due to large artery occlusion, were treated later and had differing ancillary management, there was no significant difference in 90-day modified Rankin scale scores 2-6 (55.6% vs 47.8%; OR, adjusted for baseline and management factors 0.87 (95% CI 0.71 to 1.07; p=0.20)) and risk of sICH (Safe Implementation of Thrombolysis in Stroke-Monitoring Study criteria: 1.4% vs 1.8%; p=0.12) compared with non-China participants. There was no heterogeneity in the treatment effects of low-dose versus standard-dose alteplase between China and non-China participants. Conclusion: Patients with AIS recruited to the ENCHANTED trial in China had similar outcomes in response to thrombolysis treatment despite significantly differing demographic, clinical and management factors to patients with AIS in other regions.
Clinical prediction algorithm (BRAIN) to determine risk of hematoma growth in acute intracerebral hemorrhage
(American Heart Association, Inc., 2015) Wang, Xia; Arima, Hisatomi; Al-Shahi Salman, Rustam; Woodward, Mark; Heeley, Emma; Stapf, Christian; Lavados, Pablo; Thompson, Robinson; Huang, Yining; Wang, Jiguang; Delcourt, Candice; Anderson, Craig; INTERACT Investigators
BACKGROUND AND PURPOSE: We developed and validated a simple algorithm to predict the risk of hematoma growth in acute spontaneous intracerebral hemorrhage (ICH) to better inform clinicians and researchers in their efforts to improve outcomes for patients. METHODS: We analyzed data from the computed tomography substudies of the pilot and main phases of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trials (INTERACT1 and 2, respectively). The study group was divided into a derivation cohort (INTERACT2, n=964) and a validation cohort (INTERACT1, n=346). Multivariable logistic regression was used to identify factors associated with clinically significant (≥6 mL) increase in hematoma volume at 24 hours after symptom onset. A parsimonious risk score was developed on the basis of regression coefficients derived from the logistic model. RESULTS: A 24-point BRAIN score was derived from INTERACT2 (C-statistic, 0.73) based on baseline ICH volume (mL per score, ≤10=0, 10-20=5, >20=7), recurrent ICH (yes=4), anticoagulation with warfarin at symptom onset (yes=6), intraventricular extension (yes=2), and number of hours to baseline computed tomography from symptom onset (≤1=5, 1-2=4, 2-3=3, 3-4=2, 4-5=1, >5=0) predicted the probability of ICH growth (ranging from 3.4% for 0 point to 85.8% for 24 points) with good discrimination (C-statistic, 0.73) and calibration (Hosmer-Lemeshow P=0.82) in INTERACT1. CONCLUSIONS: The simple BRAIN score predicts the probability of hematoma growth in ICH. This could be used to improve risk stratification for research and clinical practice.
Cluster-Randomized, Crossover Trial of Head Positioning in Acute Stroke
(Massachusetts Medical Society, 2017) Anderson, Craig; Arima, Hisatomi; Lavados, Pablo; Billot, Laurent; Hackett, Maree; Olavarría, Verónica; Muñoz Venturelli, Paula; Brunser, Alejandro; Peng, Bin; Cui, Liying; Song, Lily; Rogers, Kris; Middleton, Sandy; Lim, Joyce Y.; Forshaw, Denise; Lightbody, Elizabeth; Woodward, Mark; Pontes-Neto, Octavio; De Silva, Asita; Lin, Ruey-Tay; Lee, Tsong-Hai; Pandian, Jeyaraj D.; Mead, Gillian E.; Robinson, Thompson; Watkins, Caroline; HeadPoST Investigators and Coordinators
BACKGROUND: The role of supine positioning after acute stroke in improving cerebral blood flow and the countervailing risk of aspiration pneumonia have led to variation in head positioning in clinical practice. We wanted to determine whether outcomes in patients with acute ischemic stroke could be improved by positioning the patient to be lying flat (i.e., fully supine with the back horizontal and the face upwards) during treatment to increase cerebral perfusion. METHODS: In a pragmatic, cluster-randomized, crossover trial conducted in nine countries, we assigned 11,093 patients with acute stroke (85% of the strokes were ischemic) to receive care in either a lying-flat position or a sitting-up position with the head elevated to at least 30 degrees, according to the randomization assignment of the hospital to which they were admitted; the designated position was initiated soon after hospital admission and was maintained for 24 hours. The primary outcome was degree of disability at 90 days, as assessed with the use of the modified Rankin scale (scores range from 0 to 6, with higher scores indicating greater disability and a score of 6 indicating death). RESULTS: The median interval between the onset of stroke symptoms and the initiation of the assigned position was 14 hours (interquartile range, 5 to 35). Patients in the lying-flat group were less likely than patients in the sitting-up group to maintain the position for 24 hours (87% vs. 95%, P<0.001). In a proportional-odds model, there was no significant shift in the distribution of 90-day disability outcomes on the global modified Rankin scale between patients in the lying-flat group and patients in the sitting-up group (unadjusted odds ratio for a difference in the distribution of scores on the modified Rankin scale in the lying-flat group, 1.01; 95% confidence interval, 0.92 to 1.10; P=0.84). Mortality within 90 days was 7.3% among the patients in the lying-flat group and 7.4% among the patients in the sitting-up group (P=0.83). There were no significant between-group differences in the rates of serious adverse events, including pneumonia. CONCLUSIONS: Disability outcomes after acute stroke did not differ significantly between patients assigned to a lying-flat position for 24 hours and patients assigned to a sitting-up position with the head elevated to at least 30 degrees for 24 hours. (Funded by the National Health and Medical Research Council of Australia; HeadPoST ClinicalTrials.gov number, NCT02162017.)
Degree and Timing of Intensive Blood Pressure Lowering on Hematoma Growth in Intracerebral Hemorrhage: Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial-2 Results
(American Heart Association, Inc., 2016) Carcel, Cheryl; Wang, Xia; Sato, Shoichiro; Stapf, Christian; Sandset, Else; Delcourt, Candice; Arima, Hisatomi; Thompson, Robinson; Lavados, Pablo; Chalmers, John; Anderson, Craig; INTERACT2 Investigators
BACKGROUND AND PURPOSE: Degree and timing of blood pressure (BP) lowering treatment in relation to hematoma growth were investigated in the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial-2 (INTERACT2). METHODS: INTERACT2 was an international clinical trial of intensive (target systolic BP [SBP], <140 mm Hg) versus guideline-recommended (SBP, <180 mm Hg) BP lowering in 2839 patients within 6 hours of spontaneous intracerebral hemorrhage and elevated SBP (150-220 mm Hg), in which 964 had repeat cranial computed tomography at 24 hours. ANCOVA models assessed categories of SBP reduction and time to target SBP on 24-hour hematoma growth. RESULTS: Greater SBP reduction was associated with reduced hematoma growth (13.3, 5.0, and 3.0 mL for <10, 10-20, and ≥20 mm Hg, respectively; P trend<0.001). In the intensive treatment group (n=491), the least mean hematoma growth was in patients who achieved target SBP <1 hour (2.6 mL) versus to those in target at 1 to 6 (4.7 mL) and >6 hours (5.4 mL). The smallest mean absolute hematoma growth (2.0 mL) was in those achieving target SBP 5 to 8 times versus 3 to 4 (3.1 mL) and 0 to 2 times (5.2 mL). CONCLUSIONS: Intensive BP lowering with greater SBP reduction, which is achieved quickly and maintained consistently, seems to provide protection against hematoma growth for 24 hours. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00716079
Dysphagia screening and risks of pneumonia and adverse outcomes after acute stroke: An international multicenter study
(Sage, 2019-06) Ouyang, Menglu; Boaden, Elizabeth; Arima, Hisatomi; Lavados, Pablo; Billot, Laurent; Hackett, Maree; Olavarría, Verónica; Muñoz Venturelli, Paula; Song, Lili; Rogers, Kris; Middleton, Sandy; Pontes-Neto, Octavio; Lee, Tsong-Hai; Watkins, Caroline; Robinson, Thompson; Anderson, Craig
Background Dysphagia is associated with aspiration pneumonia after stroke. Data are limited on the influences of dysphagia screen and assessment in clinical practice. Aims To determine associations between a “brief” screen and “detailed” assessment of dysphagia on clinical outcomes in acute stroke patients. Methods A prospective cohort study analyzed retrospectively using data from a multicenter, cluster cross-over, randomized controlled trial (Head Positioning in Acute Stroke Trial [HeadPoST]) from 114 hospitals in nine countries. HeadPoST included 11,093 acute stroke patients randomized to lying-flat or sitting-up head positioning. Herein, we report predefined secondary analyses of the association of dysphagia screening and assessment and clinical outcomes of pneumonia and death or disability (modified Rankin scale 3–6) at 90 days. Results Overall, 8784 (79.2%) and 3917 (35.3%) patients were screened and assessed for dysphagia, respectively, but the frequency and timing for each varied widely across regions. Neither use of a screen nor an assessment for dysphagia was associated with the outcomes, but their results were compared to “screen-pass” patients, those who failed had higher risks of pneumonia (adjusted odds ratio [aOR] = 3.00, 95% confidence interval [CI] = 2.18–4.10) and death or disability (aOR = 1.66, 95% CI = 1.41–1.95). Similar results were evidence for the results of an assessment for dysphagia. Subsequent feeding restrictions were related to higher risk of pneumonia in patients failed dysphagia screen or assessment (aOR = 4.06, 95% CI = 1.72–9.54). Conclusions Failing a dysphagia screen is associated with increased risks of pneumonia and poor clinical outcome after acute stroke. Further studies concentrate on determining the effective subsequent feeding actions are needed to improve patient outcomes.
Early Blood Pressure Lowering Does Not Reduce Growth of Intraventricular Hemorrhage following Acute Intracerebral Hemorrhage: Results of the INTERACT Studies
(Karger, 2016) Chan, Edward; Anderson, Craig; Wang, Xia; Arima, Hisatomi; Saxena, Anubhav; Moullaali, Tom; Delcourt, Candice; Wu, Guojun; Wang, Jinchao; Chen, Guofang; Lavados, Pablo; Stampf, Christian; Robinson, Thompson; Chalmers, John
Background Intraventricular hemorrhage (IVH) extension is common following acute intracerebral hemorrhage (ICH) and is associated with poor prognosis. Aim To determine whether intensive blood pressure (BP)-lowering therapy reduces IVH growth. Methods Pooled analyses of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trials (INTERACT1 and INTERACT2) computed tomography (CT) substudies; multicenter, open, controlled, randomized trials of patients with acute spontaneous ICH and elevated systolic BP, randomly assigned to intensive (<140 mm Hg) or guideline-based (<180 mm Hg) BP management. Participants had blinded central analyses of baseline and 24-hour CT. Association of BP lowering to IVH growth was assessed in analysis of covariance. Results There was no significant difference in adjusted mean IVH growth following intensive (n = 228) compared to guideline-recommended (n = 228) BP treatment (1.6 versus 2.2 ml, respectively; p = 0.56). Adjusted mean IVH growth was nonsignificantly greater in patients with a mean achieved systolic BP ≥160 mm Hg over 24 h (3.94 ml; p trend = 0.26). Conclusions Early intensive BP-lowering treatment had no clear effect on IVH in acute ICH.
Early blood pressure lowering in patients with intracerebral haemorrhage and prior use of antithrombotic agents: pooled analysis of the INTERACT studies
(BMJ Publishing Group, 2016) Song, Lili; Sandset, Else Charlotte; Arima, Hisatomi; Heeley, Emma; Delcourt, Candice; Chen, Guofeng; Yang, Jie; Wu, Guojun; Wang, Xia; Lavados, Pablo; Huang, Yining; Stampf, Christian; Wang, Jiguang; Robinson, Thompson; Chalmers, John; Lindley, Richard; Anderson, Craig
OBJECTIVE: Antithrombotic agents increase risks of intracerebral haemorrhage (ICH) and associated adverse outcomes. We determined differential effects of early blood pressure (BP) lowering in patients with/without antithrombotic-associated ICH in the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trials (INTERACT1 and 2). DESIGN: Post hoc pooled analyses of the INTERACT studies-international, multicentre, prospective, open, blinded end point trials of patients with ICH (<6 h) and elevated systolic BP (SBP 150-180 mm Hg) randomly assigned to intensive (target SBP <140 mm Hg) or guideline-based (SBP <180 mm Hg) BP management. Associations of antithrombotic use and (1) death or dependency (modified Rankin scale scores 3-6) were analysed using logistic regression, and (2) of increased haematoma+intraventricular haemorrhage volume (IVH) with/without intraventricular haemorrhage (IVH) over 24 h were estimated in analyses of covariance. RESULTS: In all, 3184 patients were included in these analyses. Antithrombotic-associated ICH (364 patients, 11%) was not associated with a significantly increased risk of death or dependency (OR 1.38, 95% CI 0.93 to 2.04). There was no heterogeneity in the BP-lowering treatment effect on death or dependency. Among 1309 patients who underwent follow-up CT after 24 h, absolute increase in haematoma±IVH volume was larger (5.2/5.0 mL) in those with compared to those without prior antithrombotics (2.2/0.9 mL; p=0.022/0.031). Intensive BP lowering reduced haematoma±IVH growth by 4.7/7.1 mL in patients on antithrombotics versus 1.3/1.4 mL in those without, although these differences did not reach statistical significance (p homogeneity=0.104/0.059). CONCLUSIONS: In patients with ICH, prior antithrombotic therapy is associated with greater haematoma growth, which may be reduced by early intensive BP-lowering treatment.
Estimated GFR and the effect of intensive blood pressure lowering after acute intracerebral hemorrhage
(Elsevier, 2016) Zheng, Danni; Sato, Shoichiro; Arima, Hisatomi; Heeley, Emma; Delcourt, Candice; Cao, Yongjun; Chalmers, John; Anderson, Craig
BACKGROUND: The kidney-brain interaction has been a topic of growing interest. Past studies of the effect of kidney function on intracerebral hemorrhage (ICH) outcomes have yielded inconsistent findings. Although the second, main phase of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2) suggests the effectiveness of early intensive blood pressure (BP) lowering in improving functional recovery after ICH, the balance of potential benefits and harms of this treatment in those with decreased kidney function remains uncertain. STUDY DESIGN: Secondary analysis of INTERACT2, which randomly assigned patients with ICH with elevated systolic BP (SBP) to intensive (target SBP<140mmHg) or contemporaneous guideline-based (target SBP<180mmHg) BP management. SETTING & PARTICIPANTS: 2,823 patients from 144 clinical hospitals in 21 countries. PREDICTORS: Admission estimated glomerular filtration rates (eGFRs) of patients were categorized into 3 groups based on the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine equation: normal or high, mildly decreased, and moderately to severely decreased (>90, 60-90, and <60mL/min/1.73m(2), respectively). OUTCOMES: The effect of admission eGFR on the primary outcome of death or major disability at 90 days (defined as modified Rankin Scale scores of 3-6) was analyzed using a multivariable logistic regression model. Potential effect modification of intensive BP lowering treatment by admission eGFR was assessed by interaction terms. RESULTS: Of 2,623 included participants, 912 (35%) and 280 (11%) had mildly and moderately/severely decreased eGFRs, respectively. Patients with moderately/severely decreased eGFRs had the greatest risk for death or major disability at 90 days (adjusted OR, 1.82; 95% CI, 1.28-2.61). Effects of early intensive BP lowering were consistent across different eGFRs (P=0.5 for homogeneity). LIMITATIONS: Generalizability issues arising from a clinical trial population. CONCLUSIONS: Decreased eGFR predicts poor outcome in acute ICH. Early intensive BP lowering provides similar treatment effects in patients with ICH with decreased eGFRs.
Ethnicity and Other Determinants of Quality of Functional Outcome in Acute Ischemic Stroke
(2020) Chen, Xiaoying; Wang, Xia; Delcourt, Candice; Li, Jingwei; Arima, Hisatomi; Hackett, Maree L; Lavados, Pablo; Lindley, Richard I.; Chalmers, John; Robinson, Thompson; Anderson, Craig S.
Background and Purpose— Patient-centered outcomes are important. We aimed to determine predictors of health-related quality of life (HRQoL) and develop utility-weighted modified Rankin Scale (mRS) scores in thrombolyzed acute ischemic stroke patients from both arms of ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study). Methods— ENCHANTED was an international quasi-factorial clinical trial of different doses of intravenous alteplase and intensities of blood pressure control in acute ischemic stroke patients, with outcomes on the 5-Dimensional European Quality of Life Scale and mRS assessed at 90 days post-randomization. Logistic regression models were used to identify baseline predictors of poor HRQoL (≤mean 5-Dimensional European Quality of Life Scale utility scores). Ordinary least squares regression derived utility-weighted mRS scores. Results— In 4016 acute ischemic stroke patients with complete 5-Dimensional European Quality of Life Scale and mRS data, independent predictors of poor HRQoL were older age (odds ratio, 1.19 [95% CI, 1.12–1.27], per 10-year increase), non-Asian ethnicity (1.91 [1.61–2.27]), greater stroke severity on the National Institutes of Health Stroke Scale (1.11 [1.09–1.12]), diabetes mellitus (1.41 [1.18–1.69]), premorbid disability (mRS score 1 versus 0; 1.62 [1.33–1.97]), large vessel atheromatous pathogenesis (1.32 [1.12–1.54]), and proxy respondent (2.35 [2.01–2.74]). Sensitivity analyses indicate the ethnicity influence on HRQoL was driven by the high proportion of Chinese (62.9% of Asian) participants with better HRQoL compared with non-Chinese or other Asian groups. Derived utility values across mRS scores 0 to 5 were 0.977, 0.885, 0.748, 0.576, 0.194, and −0.174, respectively. Correlations between mRS and 5-Dimensional European Quality of Life Scale scores were stronger in Asians. Conclusions— HRQoL is worse after thrombolyzed acute ischemic stroke in the elderly, non-Asians, with greater initial severity, diabetes mellitus, premorbid disability, due to large vessel atheroma, and proxy assessment. The broader significance of better HRQoL in Asians is tempered by Chinese participants dominating analyses. From utility-weighted mRS scores indicating the greatest steps in mRS scores are between 5 and 3, treatments to avoid major disability provide the greatest benefits for patients.
Flat-head positioning increases cerebral blood flow in anterior circulation acute ischemic stroke. A cluster randomized phase IIb trial.
(Sage Publications, 11/09/2017) Olavarria, Veronica; Lavados, Pablo; Muñoz Venturelli, Paula; Gonzalez, Francisca; Gaete, Javier; Martins, Sheila; Arima, Hisatomi; Anderson, Craig; Brunser, Alejandro
Background Whether lying-flat improves blood flow in patients with acute ischemic stroke is unknown. Our aim was to investigate if lying-flat "changes" cerebral blood flow velocities assessed by transcranial Doppler in acute ischemic stroke patients. Methods In a multicenter cluster clinical trial, we randomly assigned patients within 12 h from onset of a neurological deficit due to cerebral ischemia of the anterior circulation to lying-flat or upright head positioning. The primary outcome was a change of 8 cm/s or more in mean cerebral blood flow velocities on transcranial Doppler to the middle cerebral artery at 1 and 24 h post-randomization, adjusted for imbalance in baseline variables. Secondary outcomes included serious adverse events and physical functioning at 90 days. Results Ninety-four of 304 patients screened were recruited. The primary outcome occurred in 11 (26%) of 43 patients in the lying-flat group and in 6 (12%) of 51 in the upright group at 1 h (adjusted odds ratio, 3.81; 95% CI, 1.07 to 13.54), and in 23 (53%) and 18 (36%) patients in these respective groups at 24 h (adjusted odds ratio, 3.04; 95% CI, 1.08 to 8.53). There were no between-group differences in serious adverse events, including pneumonia, heart failure or mortality, nor in functional outcome at 3 months (adjusted common odds ratio, 1.38; 95% CI 0.64 to 3.00). Conclusion The lying-flat head position was associated with a significant increase in cerebral blood flow velocities at one and 24 h within the ipsilateral hemisphere of anterior circulation acute ischemic stroke, without serious safety concerns. Clinical trial registration-URL: http://www.clinicaltrials.gov . Unique identifier: NCT01706094.
Frequency, determinants, and effects of early seizures after thrombolysis for acute ischemic stroke: The ENCHANTED trial
(Lippincott Williams & Wilkins, 2017) Xu, Ying; Hackett, Maree; Chalmers, John; Lindley, Richard; Wang, Xia; Li, Qiang; Robinson, Thompson; Arima, Hisatomi; Lavados, Pablo; Anderson, Craig; For the ENCHANTED Study Group
BACKGROUND: Seizures after ischemic stroke have not been well-studied. We aim to determine the frequency, determinants, and significance of early seizures after thrombolysis for acute ischemic stroke. METHODS: Data are from the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED), an international, multicenter, randomized controlled trial where patients with acute ischemic stroke were randomized to low-dose (0.6 mg/kg) or standard-dose (0.9 mg/kg) IV alteplase. The protocol prespecified prospective data collection on in-hospital seizures over 7 days postrandomization. Logistic regression models were used to determine variables associated with seizures and their significance on poor outcomes of death or disability (modified Rankin scale scores 3-6), symptomatic intracerebral hemorrhage (sICH), and European Quality of Life 5-Dimensions questionnaire [EQ-5D] over 90 days. RESULTS: Data were available for 3,139 acute ischemic stroke participants, of whom 42 (1.3%) had seizures at a median 22.7 hours after the onset of symptoms. Baseline variables associated with seizures were male sex (odds ratio [OR] 2.19, 95% confidence interval [CI] 1.07-4.50), severe neurologic impairment (NIH Stroke Scale score ≥10; OR 2.16, 95% CI 1.06-4.40), and fever (OR 4.55, 95% CI 2.37-8.71). Seizures independently predicted poor recovery: death or major disability (OR 2.88, 95% CI 1.28-6.47), unfavorable ordinal shift of mRS scores (OR 1.94, 95% CI 1.10-3.39), and lower than median EQ-5D health utility index score (OR 3.50, 95% CI 1.37-8.91). There was no association of seizures with sICH in adjusted analysis. CONCLUSIONS: In thrombolysis-treated patients with acute ischemic stroke, seizures are uncommon, occur early, and predict poor recovery.
Head position and cerebral blood flow in acute ischemic stroke patients: protocol for the pilot phase, cluster randomized, Head Position in Acute Ischemic Stroke Trial (HeadPoST pilot)
(Sage Publications, 2016) Brunser, Alejandro; Muñoz Venturelli, Paula; Lavados, Pablo; Gaete, Javier; Martins, Sheila; Arima, Hisatomi; Anderson, Craig; Olavarría, Verónica
RATIONALE: Few proven interventions exist for acute ischemic stroke (AIS), and most are expensive and restricted in applicability. Lying flat 'head down' positioning of AIS patients has been shown to increase by as much as 20%, mean cerebral blood flow velocities (CBFV) measured by transcranial Doppler (TCD) but whether this translates into clinical improvement is uncertain. AIM: To determine if the lying flat position increases mean CBFV in the affected territory as compared to the sitting up position in AIS patients. METHODS AND DESIGN: Head Position in Acute Ischemic Stroke Trial (HeadPoST pilot) is a cluster randomized (clusters being months), assessor-blinded end-point, phase IIb trial, where consecutive adults with anterior circulation AIS within 12 h of symptom onset are positioned to a randomized position for 48 h with TCD performed serially. STUDY OUTCOMES: Primary outcome is mean CBFV on TCD at 1 and 24 h after positioning. Secondary outcomes include: serious adverse events, neurological impairment at seven days, and death and disability at 90 days. SAMPLE SIZE ESTIMATES: Assuming an increase of 8.3 (SD 11.4) cm/s in average of mean CBFV when tilted from 30° to 0°, 46 clusters are required (92 patients in total) to detect a 20% increase of mean CBFV with 90% power and 5% level of significance. CONCLUSION: HeadPoST pilot is a cluster randomized multicenter clinical trial investigating the effect of head positioning on mean CBFV in anterior circulation AIS.
Head position and cerebral blood flow velocity in acute ischemic stroke: a systematic review and meta-analysis.
(Karger, 2014) Lavados, Pablo; Heritier, Stephane; Muñoz Venturelli, Paula; Brunser, Alejandro; Anderson, Craig; Arima, Hisatomi; Olavarría, Verónica
BACKGROUND: Patients with acute ischemic stroke (AIS) have impaired vasomotor reactivity, especially in the affected cerebral hemisphere, such that they may depend directly on systemic blood pressure to maintain perfusion to vulnerable 'at risk' penumbral tissue. As the sitting up position may affect cerebral perfusion by decreasing cerebral blood flow (CBF) in salvageable tissue, positioning AIS patients with their head in a lying flat position could increase CBF through collateral circulation or gravitational force. We wished to quantify the effect of different head positions on mean flow velocity (MFV) by transcranial Doppler ultrasonography (TCD) in AIS patients to assess the potential for benefit (or harm) of head positioning in a clinical trial. METHODS: We performed a systematic review and meta-analysis of observational studies with TCD to evaluate differences in cerebral MFV between the lying flat and sitting up head positions in AIS. For each study and each comparison, we obtained the mean value of changes in MFV and its variance. RESULTS: A total of 303 studies were identified, but 298 were excluded for varying reasons; 4 papers met the inclusion criteria and 57 patients were included in the meta-analysis for calculation of the overall mean difference in MFV. We found a significant increase in MFV from a bed angle of 30 to 15° (4.6 cm/s, 95% confidence interval, CI, 2.9-6.2, p < 0.001) and from 30 to 0° (8.3 cm/s, 95% CI 5.3-11.3, p < 0.001) in the affected hemisphere but not on the normal side in AIS patients. CONCLUSIONS: In AIS patients, MFV increased significantly in the side affected by the stroke but not in the unaffected side when they were positioned in a lying flat head position at 0 or 15° compared to an upright head position at 30°. The clinical significance of these findings is now undergoing further randomized evaluation in the international multicenter Head Position in Acute Stroke Trial (HeadPoST).
Head Position in Stroke Trial (HeadPoST) - sitting-up vs lying-flat positioning of patients with acute stroke: study protocol for a cluster randomised controlled trial
(Biomed Central Ltd., 2015) Muñoz, Paula; Arima, Hisatomi; Lavados, Pablo; Brunser, Alejandro; Peng, Bin; Cui, Liying; Song, Lily; Billot, Laurent; Boaden, Elizabeth; Hackett, Maree; Heritier, Stephane; Stephen, Jan; Middleton, Sandy; Olavarría, Verónica; Lim, Joyce; Lyndle, Richard; Heeley, Emma; Thompson, Robinson; Pontes, Octavio; Natsagdorj, Lkhamtsoo; Ruey-Tay, Lin; Watkins, Caroline; Anderson, Craig
BACKGROUND: Positioning a patient lying-flat in the acute phase of ischaemic stroke may improve recovery and reduce disability, but such a possibility has not been formally tested in a randomised trial. We therefore initiated the Head Position in Stroke Trial (HeadPoST) to determine the effects of lying-flat (0°) compared with sitting-up (≥ 30°) head positioning in the first 24 hours of hospital admission for patients with acute stroke. METHODS/DESIGN: We plan to conduct an international, cluster randomised, crossover, open, blinded outcome-assessed clinical trial involving 140 study hospitals (clusters) with established acute stroke care programs. Each hospital will be randomly assigned to sequential policies of lying-flat (0°) or sitting-up (≥ 30°) head position as a 'business as usual' stroke care policy during the first 24 hours of admittance. Each hospital is required to recruit 60 consecutive patients with acute ischaemic stroke (AIS), and all patients with acute intracerebral haemorrhage (ICH) (an estimated average of 10), in the first randomised head position policy before crossing over to the second head position policy with a similar recruitment target. After collection of in-hospital clinical and management data and 7-day outcomes, central trained blinded assessors will conduct a telephone disability assessment with the modified Rankin Scale at 90 days. The primary outcome for analysis is a shift (defined as improvement) in death or disability on this scale. For a cluster size of 60 patients with AIS per intervention and with various assumptions including an intracluster correlation coefficient of 0.03, a sample size of 16,800 patients at 140 centres will provide 90 % power (α 0.05) to detect at least a 16 % relative improvement (shift) in an ordinal logistic regression analysis of the primary outcome. The treatment effect will also be assessed in all patients with ICH who are recruited during each treatment study period. DISCUSSION: HeadPoST is a large international clinical trial in which we will rigorously evaluate the effects of different head positioning in patients with acute stroke.
Head Position in the Early Phase of Acute Ischemic Stroke: An International Survey of Current Practice
(National Stroke Association. Published by Elsevier Inc., 2015) Muñoz, Paula; Olavarría, Verónica; González, Francisca; Brunser, Alejandro; Lavados, Pablo; Arima, Hisatomi; Anderson, Craig
BACKGROUND: Evidence to recommend a specific head position for patients in the early phase of acute ischemic stroke (AIS) is scarce. The aim of this study was to assess current head position practice for AIS patients among physicians from hospitals in different countries. METHODS: A cross-sectional survey research design was used; physicians who are part of a stroke research network were invited to participate by e-mail. Descriptive statistics were used. RESULTS: An invitation to participate was delivered to 298 doctors from 16 countries and 42.9% completed all survey questions. Participant responses were evenly divided in sitting up and lying flat position as the most usual at their hospital: 52.8% (95% confidence interval [CI], 43.7-61.0) of respondents preferred sitting up, whereas 47.2% (95% CI, 38.2-55.5) preferred lying flat; 53.9% (95% CI, 45.3-62.5) of participants answered that no written protocol specifying the indicated head position for stroke patients was available at their hospital or department, and 71% (95% CI, 63.2-78.9) recognized being uncertain about the best position for AIS patients. CONCLUSIONS: Common practice differs between physicians, and there is a lack of consensus about the best strategy regarding head position for AIS patients in many countries. An opportunity exists for a randomized trial to resolve this uncertainty and develop evidence-based consensus protocols to improve patient management and outcomes.

Browsing by Author "Arima, Hisatomi"

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