Objective: It is not known whether patients with atrial fibrillation (AF) with ischemic stroke despite oral anticoagulant therapy are at increased risk for further recurrent strokes or how ongoing secondary prevention should be managed.Methods: We conducted an individual patient data pooled analysis of 7 prospective cohort studies that recruited patients with AF and recent cerebral ischemia. We compared patients taking oral anticoagulants (vitamin K antagonists [VKA] or direct oral anticoagulants [DOAC]) prior to index event (OAC_prior) with those without prior oral anticoagulation (OAC_naive). We further compared those who changed the type (ie, from VKA or DOAC, vice versa, or DOAC to DOAC) of anticoagulation (OAC_changed) with those who continued the same anticoagulation as secondary prevention (OAC_unchanged). Time to recurrent acute ischemic stroke (AIS) was analyzed using multivariate competing risk Fine–Gray models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).Results: We included 5,413 patients (median age = 78 years [interquartile range (IQR) = 71–84 years]; 5,136 [96.7%] had ischemic stroke as the index event, median National Institutes of Health Stroke Scale on admission = 6 [IQR = 2–12]). The median CHA₂DS₂‐Vasc score (congestive heart failure, hypertension, age≥ 75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65–74 years, sex category) was 5 (IQR = 4–6) and was similar for OAC_prior (n = 1,195) and OAC_naive (n = 4,119, p = 0.103). During 6,128 patient‐years of follow‐up, 289 patients had AIS (4.7% per year, 95% CI = 4.2–5.3%). OAC_prior was associated with an increased risk of AIS (HR = 1.6, 95% CI = 1.2–2.3, p = 0.005). OAC_changed (n = 307) was not associated with decreased risk of AIS (HR = 1.2, 95% CI = 0.7–2.1, p = 0.415) compared with OAC_unchanged (n = 585).Interpretation: Patients with AF who have an ischemic stroke despite previous oral anticoagulation are at a higher risk for recurrent ischemic stroke despite a CHA₂DS₂‐Vasc score similar to those without prior oral anticoagulation. Better prevention strategies are needed for this high‐risk patient group. ANN NEUROL 2020;87:677–687

Background and Purpose—: Blood pressure (BP) lowering is often conducted as part of general acute management in patients with acute intracerebral hemorrhage. However, the relationship between BP after antihypertensive therapy and clinical outcomes is not fully known. Methods—: Hyperacute (180 mm Hg were included. All patients received intravenous antihypertensive treatment, based on predefined protocol to lower and maintain SBP between 120 and 160 mm Hg. BPs were measured every 15 minutes during the initial 2 hours and every 60 minutes in the next 22 hours (a total of 30 measurements). The mean achieved SBP was defined as the mean of 30 SBPs, and associations between the mean achieved SBP and neurological deterioration (≥2 points’ decrease in Glasgow Coma Score or ≥4 points’ increase in National Institutes of Health Stroke Scale score), hematoma expansion (>33% increase), and unfavorable outcome (modified Rankin Scale score 4–6 at 3 months) were assessed with multivariate logistic regression analyses. Results—: Of the 211 patients (81 women, median age 65 [interquartile range, 58–74] years, and median initial National Institutes of Health Stroke Scale score 13 [8–17]) enrolled, 17 (8%) showed neurological deterioration, 36 (17%) showed hematoma expansion, and 87 (41%) had an unfavorable outcome. On multivariate regression analyses, mean achieved SBP was independently associated with neurological deterioration (odds ratio, 4.45; 95% confidence interval, 2.03–9.74 per 10 mm Hg increment), hematoma expansion (1.86; 1.09–3.16), and unfavorable outcome (2.03; 1.24–3.33) after adjusting for known predictive factors. Conclusions—: High achieved SBP after standardized antihypertensive therapy in hyperacute intracerebral hemorrhage was independently associated with poor clinical outcomes. Aggressive antihypertensive treatment may ameliorate clinical outcomes.

Background and Purpose—: The associations between early blood pressure (BP) variability and clinical outcomes in patients with intracerebral hemorrhage after antihypertensive therapy, recently clarified by a post hoc analysis of Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial 2 (INTERACT2), were confirmed using the Stroke Acute Management with Urgent Risk-factor Assessment and Improvement (SAMURAI)-intracerebral hemorrhage study cohort. Methods—: Patients with hyperacute (180 mm Hg were registered in a prospective, multicenter, observational study. All patients received antihypertensive therapy based on a predefined standardized protocol to lower and maintain SBP between 120 and 160 mm Hg using intravenous nicardipine. BPs were measured hourly during the initial 24 hours. BP variability was determined as SD and successive variation. The associations between BP variability and hematoma expansion (>33%), neurological deterioration within 72 hours, and unfavorable outcome (modified Rankin Scale, 4–6) at 3 months were assessed. Results—: Of the 205 patients, 33 (16%) showed hematoma expansion, 14 (7%) showed neurological deterioration, and 81 (39%) had unfavorable outcomes. The SD and successive variation of SBP were 13.8 (interquartile range, 11.5–16.8) and 14.9 (11.7–17.7) mm Hg, respectively, and those of diastolic BP were 9.4 (7.5–11.2) and 13.1 (11.2–15.9) mm Hg, respectively. On multivariate regression analyses, neurological deterioration was associated with the SD of SBP (odds ratio, 2.75; 95% confidence interval, 1.45–6.12 per quartile) and the successive variation of SBP (2.37; 1.32–4.83), and unfavorable outcome was associated with successive variation of SBP (1.42; 1.04–1.97). Hematoma expansion was not associated with any BP variability. Conclusions—: SBP variability during the initial 24 hours of acute intracerebral hemorrhage was independently associated with neurological deterioration and unfavorable outcomes. Stability of antihypertensive therapy may improve clinical outcomes.

Background: Although tortuosity of the internal carotid artery (ICA) can pose a significant challenge when performing mechanical thrombectomy, few studies have examined the impact of ICA tortuosity on mechanical thrombectomy outcomes. Methods: In a registry-based hospital cohort, consecutive patients with anterior circulation stroke in whom mechanical thrombectomy was attempted were divided into 2 groups: those with tortuosity in the extracranial or cavernous ICA (tortuous group) and those without (nontortuous group). The extracranial ICA tortuosity was defined as the presence of coiling or kinking. The cavernous ICA tortuosity was defined by the posterior deflection of the posterior genu or the shape resembling Simmons-type catheter. Outcomes included first pass effect (FPE; extended Thrombolysis in Cerebral Infarction score 2c/3 after first pass), favorable outcome (3-month modified Rankin Scale score of 0–2), and intracranial hemorrhage. Results: Of 370 patients, 124 were in the tortuous group (extracranial ICA tortuosity, 35; cavernous ICA tortuosity, 70; tortuosity at both sites, 19). The tortuous group showed a higher proportion of women and atrial fibrillation than the nontortuous group. FPE was less frequently achieved in the tortuous group than the nontortuous group (21% versus 39%; adjusted odds ratio, 0.45 [95% CI, 0.26–0.77]). ICA tortuosity was independently associated with the longer time from puncture to extended Thrombolysis in Cerebral Infarction ≥2b reperfusion (β=23.19 [95% CI, 13.44–32.94]). Favorable outcome was similar between groups (46% versus 48%; P =0.87). Frequencies of any intracranial hemorrhage (54% versus 42%; adjusted odds ratio, 1.61 [95% CI, 1.02–2.53]) and parenchymal hematoma (11% versus 6%; adjusted odds ratio, 2.41 [95% CI, 1.04–5.58]) were higher in the tortuous group. In the tortuous group, the FPE rate was similar in patients who underwent combined stent retriever and contact aspiration thrombectomy and in those who underwent either procedure alone (22% versus 19%; P =0.80). However, in the nontortuous group, the FPE rate was significantly higher in patients who underwent combined stent retriever and contact aspiration (52% versus 35%; P =0.02). Conclusions: ICA tortuosity was independently associated with reduced likelihood of FPE and increased risk of postmechanical thrombectomy intracranial hemorrhage. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02251665.

Background: The “1-3-6-12-day rule” for starting direct oral anticoagulants (DOACs) in patients with nonvalvular atrial fibrillation after acute ischemic stroke or transient ischemic attack recommends timings that may be later than used in clinical practice. We investigated more practical optimal timing of DOAC initiation according to stroke severity. Methods: The combined data of prospective registries in Japan, Stroke Acute Management with Urgent Risk-factor Assessment and Improvement-nonvalvular atrial fibrillation (September 2011 to March 2014) and RELAXED (February 2014 to April 2016) were used. Patients were divided into transient ischemic attack and 3 stroke subgroups by the National Institutes of Health Stroke Scale score: mild (0–7), moderate (8–15), and severe (≥16). The early treatment group was defined as patients starting DOACs earlier than the median initiation day in each subgroup. Outcomes included a composite of recurrent stroke or systemic embolism, ischemic stroke, and severe bleeding within 90 days. Six European prospective registries were used for validation. Results: In the 1797 derivation cohort patients, DOACs were started at median 2 days after transient ischemic attack and 3, 4, and 5 days after mild, moderate, and severe strokes, respectively. Stroke or systemic embolism was less common in Early Group (n=785)—initiating DOACS within 1, 2, 3, and 4 days, respectively—than Late Group (n=1012) (1.9% versus 3.9%; adjusted hazard ratio, 0.50 [95% CI, 0.27–0.89]), as was ischemic stroke (1.7% versus 3.2%, 0.54 [0.27–0.999]). Major bleeding was similarly common in the 2 groups (0.8% versus 1.0%). On validation, both ischemic stroke (2.4% versus 2.2%) and intracranial hemorrhage (0.2% versus 0.6%) were similarly common in Early (n=547) and Late (n=1483) Groups defined using derivation data. Conclusions: In Japanese and European populations, early DOAC initiation within 1, 2, 3, or 4 days according to stroke severity seemed to be feasible to decrease the risk of recurrent stroke or systemic embolism and no increase in major bleeding. These findings support ongoing randomized trials to better establish the optimal timing of DOAC initiation.

Background and Purpose—: Ischemic stroke associated with nonvalvular atrial fibrillation (NVAF) despite prior anticoagulation may indicate underlying problems that nullify the stroke-preventing effects of oral anticoagulants. We aimed to evaluate the risk for recurrent stroke in patients with NVAF with prior anticoagulation, compared with that in patients without prior anticoagulation. Methods—: This study comprised pooled individual patient data on NVAF-associated acute ischemic stroke or transient ischemic attack from 2011 to 2014 arising from the Clinical Research Collaboration for Stroke in Korea (15 South Korean stroke centers) and the Stroke Acute Management With Urgent Risk-Factor Assessment and Improvement-NVAF registry (18 Japanese stroke centers). Data on 4841 eligible patients from the Clinical Research Collaboration for Stroke in Korea registry were pooled with data on all patients (n=1192) in the Stroke Acute Management with Urgent Risk-factor Assessment and Improvement-NVAF registry. The primary outcome was recurrent ischemic stroke. The secondary outcomes were hemorrhagic stroke and all-cause death. Outcome events were captured up to 1 year after the index event. Results—: Among the 6033 patients in the full cohort, 5645 patients were analyzed, of whom 1129 patients (20.0%) had received prior anticoagulation. Median age was 75 years (interquartile range, 69–81 years), and 2649 patients (46.9%) were women. Follow-up data of 4617 patient-years (median follow-up 365 days, interquartile range 335–365 days) were available. The cumulative incidence of recurrent ischemic stroke in patients with prior anticoagulation was 5.3% (60/1129), compared with the 2.9% (130/4516) incidence in patients without prior anticoagulation. The risk for recurrent ischemic stroke was higher in patients with prior anticoagulation than in those without (multivariable Cox shared-frailty model, hazard ratio 1.50 [95% CI, 1.02–2.21]). No significant differences in the risks for hemorrhagic stroke and mortality were seen between the 2 groups. Conclusions—: The risk for recurrent ischemic stroke may be higher in NVAF-associated stroke patients with prior anticoagulation than in those without prior anticoagulation. Registration—: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01581502.