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Background and Purpose— We assessed whether lower-dose alteplase at 0.6 mg/kg is efficacious and safe for acute fluid-attenuated inversion recovery-negative stroke with unknown time of onset. Methods— This was an investigator-initiated, multicenter, randomized, open-label, blinded-end point trial. Patients met the standard indication criteria for intravenous thrombolysis other than a time last-known-well >4.5 hours (eg, wake-up stroke). Patients were randomly assigned (1:1) to receive alteplase at 0.6 mg/kg or standard medical treatment if magnetic resonance imaging showed acute ischemic lesion on diffusion-weighted imaging and no marked corresponding hyperintensity on fluid-attenuated inversion recovery. The primary outcome was a favorable outcome (90-day modified Rankin Scale score of 0–1). Results— Following the early stop and positive results of the WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke), this trial was prematurely terminated with 131 of the anticipated 300 patients (55 women; mean age, 74.4±12.2 years). Favorable outcome was comparable between the alteplase group (32/68, 47.1%) and the control group (28/58, 48.3%; relative risk [RR], 0.97 [95% CI, 0.68–1.41]; P =0.892). Symptomatic intracranial hemorrhage within 22 to 36 hours occurred in 1/71 and 0/60 (RR, infinity [95% CI, 0.06 to infinity]; P >0.999), respectively. Death at 90 days occurred in 2/71 and 2/60 (RR, 0.85 [95% CI, 0.06–12.58]; P >0.999), respectively. Conclusions— No difference in favorable outcome was seen between alteplase and control groups among patients with ischemic stroke with unknown time of onset. The safety of alteplase at 0.6 mg/kg was comparable to that of standard treatment. Early study termination precludes any definitive conclusions. Registration— URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02002325.

OBJECTIVECerebral hyperperfusion syndrome (CHS) is a serious complication after carotid artery stenting (CAS). Staged angioplasty (SAP)—i.e., angioplasty followed by delayed CAS—has been reported as a potential CHS-avoiding procedure. The purpose of this study was to clarify the effectiveness of SAP in avoiding CHS after carotid revascularization for patients at high risk for this complication.METHODSThe authors retrospectively studied cases involving patients at high risk for CHS from 44 Japanese centers who were scheduled for SAP, regular CAS, angioplasty, or staged procedures other than SAP between October 2007 and March 2014. They investigated the rate of CHS in the population scheduled for SAP or regular CAS, and for safety analysis, the composite rate of transient ischemic attack (TIA) and ischemic stroke in the population eventually receiving SAP or regular CAS.RESULTSData from a total of 525 patients (532 lesions, mean age 72.5 ± 7.5 years, 74 women ) were analyzed. Scheduled procedures included SAP for 113 lesions and regular CAS for 419 lesions. The rate of CHS was lower in the SAP group than in the regular CAS group (4.4% vs 10.5%, p = 0.047). Multivariate analysis showed that SAP was negatively related to CHS (OR 0.315; 95% CI 0.120–0.828). In the population eventually receiving SAP (102 lesions) or regular CAS (428 lesions), the composite rate of TIA and ischemic stroke was comparable between the SAP group and the regular CAS group (9.8% vs 9.3%).CONCLUSIONSSAP may be an effective and safe carotid revascularization procedure to avoid CHS.

Background To explore how the clinical impact of heart rate (HR) and heart rate variabilities (HRV) during the initial 24 hours after acute intracerebral hemorrhage (ICH) contribute to worse clinical outcomes. Methods and Results In the ATACH‐2 (Antihypertensive Treatment in Intracerebral Hemorrhage 2) trial, the HR was recorded for every 15 minutes from baseline to 1 hour and hourly during the initial 24 hours post‐randomization. We calculated the following: mean, standard deviation, coefficient of variation, successive variation, and average real variability (ARV). Outcomes were hematoma expansion at 24 hours and unfavorable functional outcome, defined as modified Rankin Scale score 4 to 6 at 90 days. Of the 1000 subjects in ATACH‐2, 994 with available HR data were included in the analyses. Overall, 262 experienced hematoma expansion, and 362 had unfavorable outcomes. Increased mean HR was linearly associated with unfavorable outcome (per 10 bpm increase adjusted odds ratio [aOR], 1.31, 95% CI, 1.14–1.50) but not with hematoma expansion, while HR‐ARV was associated with hematoma expansion (aOR, 1.06, 95% CI, 1.01–1.12) and unfavorable outcome (aOR, 1.07, 95% CI, 1.01–1.3). Every 10‐bpm increase in mean HR increased the probability of unfavorable outcome by 4.3%, while every 1 increase in HR‐ARV increased the probability of hematoma expansion by 1.1% and unfavorable outcome by 1.3%. Conclusions Increased mean HR and HR‐ARV within the initial 24 hours were independently associated with unfavorable outcome in acute ICH. Moreover, HR‐ARV was associated with hematoma expansion at 24 hours. This may have future therapeutic implications to accommodate HR and HRV in acute ICH. Registration URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT01176565.

ObjectiveTo determine the association between clinical outcomes and acute systolic blood pressure (SBP) levels achieved after intracerebral hemorrhage (ICH).MethodsEligible patients who were randomized to the ATACH‐2 (Antihypertensive Treatment in Intracerebral Hemorrhage 2) trial (ClinicalTrials.gov: NCT01176565) were divided into 5 groups by 10‐mmHg strata of average hourly minimum SBP (<120, 120–130, 130–140, 140–150, and ≥ 150 mmHg) during 2 to 24 hours after randomization. Outcomes included: 90‐day modified Rankin Scale (mRS) 4 to 6; hematoma expansion, defined as an increase ≥6 ml from baseline to 24‐hour computed tomography; and cardiorenal adverse events within 7 days.ResultsOf the 1,000 subjects in ATACH‐2, 995 with available SBP data were included in the analyses. The proportion of mRS 4 to 6 was 37.5, 36.0, 42.8, 38.6, and 38.0%, respectively. For the “140 to 150” group relative to the “120 to 130,” the odds ratio (OR), adjusting for sex, race, age, onset‐to‐randomization time, baseline National Institutes of Health Stroke Scale score, hematoma volume, and hematoma location, was 1.62 (95% confidence interval [CI], 1.02–2.58). Hematoma expansion was identified in 16.9, 13.7, 21.4, 18.5, and 26.4%, respectively. The 140 to 150 (OR, 1.80; 95% CI, 1.05–3.09) and “≥150” (1.98; 1.12–3.51) showed a higher frequency of expansion than the 120 to 130 group. Cardiorenal events occurred in 13.6, 16.6, 11.5, 8.1, and 8.2%, respectively. The 140 to 150 (0.43; 0.19–0.88) and ≥ 150 (0.44; 0.18–0.96) showed a lower frequency of the events than the 120 to 130.InterpretationBeneficial effects of lowering and maintaining SBP at 120 to 130 mmHg during the first 24 hours on clinical outcomes by suppressing hematoma expansion was somewhat offset by cardiorenal complications. ANN NEUROL 2019;85:105–113.