The purpose of this study was to determine the safety and efficacy of intravenous recombinant tissue-type plasminogen activator (0.6 mg/kg alteplase) within 3 hours of stroke onset in Japanese patients outside the indications in the European license.Of the 600 patients who were treated with recombinant tissue-type plasminogen activator, 422 met the inclusion criteria of the European license (IN group) and 178 did not (OUT group).The OUT group was inversely associated with any intracerebral hemorrhage (adjusted OR, 0.50; 95% CI, 0.29-0.84), positively associated with an unfavorable outcome (2.48; 1.55-3.94) and mortality (2.04; 1.02-4.04), and not associated with symptomatic intracerebral hemorrhage (0.53; 0.11-1.79) or complete independency (0.65; 0.40-1.03) after multivariate adjustment.Functional and vital outcomes 3 months after low-dose recombinant tissue-type plasminogen activator in patients outside the European indications were less favorable compared with those included in the indications; however, the risk of intracerebral hemorrhage was not.
Purpose: Intravenous nicardipine is commonly used to reduce elevated blood pressure (BP) in acute intracerebral hemorrhage (ICH). We determined factors associated with nicardipine dose and the association of the dose with clinical outcomes in hyperacute ICH. Methods: Hyperacute (<3 h from onset) ICH patients with initial systolic BP (SBP) >180 mmHg were registered in a multicenter observational study (the SAMURAI-ICH study). All patients initially received 5mg/h of intravenous nicardipine to lower BP. The dose was adjusted to maintain SBP between 120 and 160 mmHg based on BPs measured every 15 min during the initial 2 h and every 60 min in the following 22 h. Maximum hourly and total doses during the initial 24 h were calculated. Associations of the doses with neurological deterioration (a decrease of ≥2 in GCS or an increase of ≥4 in NIHSS score at 72 h after treatment initiation), hematoma expansion (>33% from baseline to 24 h), and unfavorable outcome (modified Rankin Scale score 4-6 at 3 months) were assessed. Results: Of 211 patients in the registry, 206 patients (81 women, 65.8±11.8 years old) whose nicardipine data were available throughout 24-h observation were studied. Initial BP was 201.9±15.9/107.9±15.1 mmHg. Median time to reach target SBP range was 30 min (IQR 15-45). Maximum and total doses were 9.1±4.2mg/h and 123.7±100.2mg/day, respectively. Multivariate analyses revealed that male sex [standardized regression coefficient (β)=0.20, p=0.0030 for maximum dose; β=0.25, p=0.0002 for total dose], age (β= -0.28, p=0.0002; β= -0.25, p=0.0005) and initial SBP (β=0.19, p=0.0018; β=0.18, p=0.0021) were independently associated with both maximum and total doses. Body weight (β=0.20, p=0.0084) was independently associated with total dose. After multivariate adjustment, maximum dose (per 1mg/h; OR 1.25, 95% CI 1.09-1.45; p=0.0022) was independently and total dose (per 10mg/day; OR 1.06, 95% CI 0.998-1.132; p=0.0555) tended to be associated with neurological deterioration. Nicardipine dose was not associated with hematoma expansion and unfavorable outcome. Conclusions: Nicardipine dosage is roughly predictable with sex, age, body weight and initial SBP in acute ICH. Maximum hourly nicardipine dose was associated with neurological deterioration.
Background Statins have been associated with reduced recurrence and better functional outcomes in patients with acute ischemic stroke. However, the effect of statins in patients with acute large vessel occlusion (LVO) is not well scrutinized. Methods and Results RESCUE (Recovery by Endovascular Salvage for Cerebral Ultra-Acute Embolism)-Japan Registry 2, a physician-initiated registry, enrolled 2420 consecutive patients with acute LVO who were admitted to 46 centers across Japan within 24 hours of onset. We compared patients with and without statin use after acute LVO onset (statin group and nonstatin group, respectively) in terms of the modified Rankin scale at 90 days. We estimated that the odds ratios for the primary outcome was modified Rankin scale and we estimated the odds ratios for a 1-scale lower modified Rankin scale adjusting for confounders. After excluding 12 patients without LVO and 9 patients without follow-up, the mean age of 2399 patients was 75.9 years; men accounted for 55% of patients. Statins were administered to 447 (19%) patients after acute LVO onset. Patients in the statin group had more atherothrombotic cerebral infarctions (34.2% versus 12.1%, P<0.0001), younger age (73.4 years versus 76.5 years, P<0.0001), and lower median National Institutes of Health Stroke Scale on admission (14 versus 17, P<0.0001) than the nonstatin group. The adjusted common OR of the statin group for lower modified Rankin scale was 1.29 (95% CI, 1.04-1.37; P=0.02). The mortality at 90 days was lower in the statin group (4.7%) than the nonstatin group (12.5%; P<0.0001). The adjusted OR of the statin group relative to the nonstatin group for mortality was 0.36 (95% CI, 0.21-0.62; P=0.02). Conclusions Statin administration after acute LVO onset is significantly associated with better functional outcome and mortality at 90 days.
Background and purpose The characteristics of reverse magnetic resonance angiography and diffusion‐weighted imaging ( MRA ‐ DWI ) mismatch ( RMM ), defined as a large DWI lesion in the absence of major artery occlusion ( MAO ), remain unknown, especially in patients treated with intravenous recombinant tissue plasminogen activator (rt‐ PA ). Methods Patients with stroke in the middle cerebral artery territory were included. Early ischaemic changes (EIC) were assessed with the Alberta Stroke Program Early CT Score on DWI (DWI‐ASPECTS). All patients were divided into four groups based on the presence of MAO and a DWI‐ASPECTS cut‐off value of <7. RMM was defined as DWI‐ASPECTS <7 without MAO. Clinical characteristics, symptomatic intracerebral hemorrhage ( sICH ) and favorable functional outcome (modified Rankin Scale score 0–2) at 90 days were compared amongst the four groups. Results Of the 486 patients enrolled (167 women, median age 74 years, median initial National Institutes of Health Stroke Scale score 13), reverse MRA‐DWI mismatch was observed in 24 (5%). Of the clinical characteristics, cardioembolism was the only factor that was independently associated with RMM [odds ratio (OR) 5.49, 95% confidence interval (CI) 1.25–24.1]. Multivariable analyses revealed that patients with RMM more commonly had sICH than those with DWI‐ASPECTS ≥ 7 irrespective of the presence (OR 5.44, 95% CI 1.13–26.1) or absence (13.1, 2.07–83.3) of MAO, and they had a more favorable functional outcome than those with DWI‐ASPECTS < 7 plus MAO (7.45, 2.39–23.2). Conclusion RMM was observed in 5% of patients treated with rt‐PA and associated with cardioembolism. Patients with RMM may benefit from thrombolysis compared with those with EIC with MAO, although increment in the rate of sICH is a concern.
Objective: Optimal blood pressure (BP) control in acute intracerebral hemorrhage (ICH) remains controversial. We determined the effects of SBP lowering to 160 mmHg or more using intravenous nicardipine for acute ICH patients. Methods: This is a prospective, multicenter, observational study conducted in Japan, with the lack of control groups. Patients with supratentorial ICH within 3 h of onset, admission SBP 180 mmHg or more, Glasgow Coma Scale (GCS) 5 or more, and hematoma volume less than 60 ml were initially treated with intravenous nicardipine to maintain SBP between 120 and 160 mmHg with 24-h frequent BP monitoring. The primary endpoints were neurological deterioration within 72 h [GCS decrement ≥2 points or National Institutes of Health Stroke Scale (NIHSS) increment ≥4 points; estimated 90% confidence interval (CI) on the basis of previous studies: 15.2–25.9%] and serious adverse effects (SAE) to stopping intravenous nicardipine within 24 h (1.8–8.9%). The secondary endpoints included hematoma expansion more than 33% at 24 h (17.1–28.3%), modified Rankin Scale (mRS) 4 or more (54.5–67.9%) and death at 3 months (6.0–13.5%). Results: We enrolled 211 Japanese patients (81 women, 65.6 ± 12.0 years old). At baseline, BP was 201.8 ± 15.7/107.9 ± 15.0 mmHg. Median hematoma volume was 10.2 ml (interquartile range 5.6–19.2), and NIHSS score was 13 (8–17). Neurological deterioration was identified in 17 patients (8.1%), SAE in two (0.9%), hematoma expansion in 36 (17.1%), mRS 4 or more in 87 (41.2%), and death in four (1.9%). All the results were equal to or below the estimated lower 90% CI. Conclusion: SBP lowering to 160 mmHg or less using nicardipine appears to be well tolerated and feasible for acute ICH.
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