Endovascular Thrombectomy With or Without Intravenous Thrombolysis: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: We performed this meta-analysis of randomized clinical trials to compare the outcomes in patients treated with endovascular thrombectomy who receive prior intravenous thrombolysis with those who do not receive such treatment. Recently, one randomized trial reported outcomes to address this issue, so timely update of meta-analysis is needed to determine the value of administering intravenous thrombolysis before endovascular thrombectomy. MATERIALS AND METHODS: Four randomized clinical trials are included in our meta-analysis. We calculated pooled odds ratios and 95% CIs using random-effects models. The primary efficacy endpoint was a favorable outcome defined by a modified Rankin Scale score of 0 (no symptoms), 1 (no significant disability), or 2 (slight disability) at 90 days post-randomization. Secondary endpoints analyzed were any intracerebral hemorrhage, symptomatic intracerebral hemorrhage, and mortality. RESULTS: Of the 1633 patients randomized, the proportion of patients who achieved a favorable outcome was similar between endovascular thrombectomy alone and combined approach with intravenous thrombolysis and endovascular thrombectomy (1631 patients analyzed; odds ratio 1.02; CI 0.84-1.25; p = 0.83). Risk of any intracerebral hemorrhage was significantly lower among those randomized to endovascular thrombectomy alone (1633 patients analyzed; odds ratio 0.75; CI 0.57-0.99; p = 0.04). Rates of symptomatic intracerebral hemorrhage (p = 0.36) and mortality (p = 0.62) were not significantly different between the two groups. CONCLUSIONS: Compared with endovascular thrombectomy preceded by intravenous thrombolysis, endovascular thrombectomy resulted in similar rates of favorable outcome with a lower rate of intracerebral hemorrhage. A large phase 3 trial is required to conclusively demonstrate equivalency of both approaches to guide future practice.

Clopidogrel Bolus is Inferior to Sustained Clopidogrel Pretreatment in Patients Undergoing Carotid Artery Stent Placement.

BACKGROUND: Clopidogrel bolus is an option used before carotid artery stent (CAS) placement when sustained clopidogrel pretreatment is not used. OBJECTIVE: To compare the effect of clopidogrel bolus (450 mg administered ≥4 hours) with sustained clopidogrel pretreatment (48 hours or greater) before CAS among patients recruited in the Carotid Revascularization Endarterectomy versus Stenting Trial. METHODS: We compared the rates of primary end point (either any stroke, myocardial infarction, or death during the periprocedural period or any ipsilateral stroke within 4 years) between patients who received clopidogrel bolus and those who received sustained clopidogrel pretreatment using Cox proportional hazards analysis after adjusting for age, sex, symptomatic status, and initial severity of stenosis (≥70% vs <70%) over 4 years. RESULTS: The rate of periprocedural stroke (7.3% vs 3.4%, P = .03) and primary end point (11.3% vs 5.9%, P = .02) was significantly higher among patients who received clopidogrel bolus. The risk of primary end point was significantly higher in patients who received clopidogrel bolus (hazards ratio 1.9, 95% CI 1.1-3.4, P = .02) after adjusting for potential confounders. The overall mean (±standard deviation) primary end point-free survival based on Kaplan-Meier analysis was 7.0 ± 0.2 years for patients who received clopidogrel bolus and 8.9 ± 0.1 years for those who received sustained clopidogrel pretreatment (log-rank test P = .011). CONCLUSION: Clopidogrel bolus was associated with higher rates of adverse outcomes compared with sustained clopidogrel pretreatment in patients who underwent CAS. Therefore, clopidogrel bolus may not be equivalent to sustained clopidogrel pretreatment.

Reinfection With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Patients Undergoing Serial Laboratory Testing.

BACKGROUND: A better understanding of reinfection after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become one of the healthcare priorities in the current pandemic. We determined the rate of reinfection, associated factors, and mortality during follow-up in a cohort of patients with SARS-CoV-2 infection. METHODS: We analyzed 9119 patients with SARS-CoV-2 infection who received serial tests in total of 62 healthcare facilities in the United States between 1 December 2019 and 13 November 2020. Reinfection was defined by 2 positive tests separated by interval of >90 days and resolution of first infection was confirmed by 2 or more consecutive negative tests. We performed logistic regression analysis to identify demographic and clinical characteristics associated with reinfection. RESULTS: Reinfection was identified in 0.7% (n = 63, 95% confidence interval [CI]: .5%-.9%) during follow-up of 9119 patients with SARS-CoV-2 infection. The mean period (±standard deviation [SD]) between 2 positive tests was 116 ± 21 days. A logistic regression analysis identified that asthma (odds ratio [OR] 1.9, 95% CI: 1.1-3.2) and nicotine dependence/tobacco use (OR 2.7, 95% CI: 1.6-4.5) were associated with reinfection. There was a significantly lower rate of pneumonia, heart failure, and acute kidney injury observed with reinfection compared with primary infection among the 63 patients with reinfection There were 2 deaths (3.2%) associated with reinfection. CONCLUSIONS: We identified a low rate of reinfection confirmed by laboratory tests in a large cohort of patients with SARS-CoV-2 infection. Although reinfection appeared to be milder than primary infection, there was associated mortality.

Effect of Moderate and Severe Persistent Hyperglycemia on Outcomes in Patients With Intracerebral Hemorrhage.

BACKGROUND: We evaluated the effect of persistent hyperglycemia on outcomes in 1000 patients with intracerebral hemorrhage enrolled within 4.5 hours of symptom onset. METHODS: We defined moderate and severe hyperglycemia based on serum glucose levels ≥140 mg/dL-<180 and ≥180 mg/dL, respectively, measured at baseline, 24, 48, and 72 hours. Persistent hyperglycemia was defined by 2 consecutive (24 hours apart) serum glucose levels. We evaluated the relationship between moderate and severe hyperglycemia and death or disability (defined by modified Rankin Scale score of 4-6) at 90 days in the overall cohort and in groups defined by preexisting diabetes. RESULTS: In the multivariate analysis, both moderate (odds ratio, 1.8 [95% CI, 1.1-2.8]) and severe (odds ratio, 1.8 [95% CI, 1.2-2.7]) hyperglycemia were associated with higher 90-day death or disability after adjusting for Glasgow Coma Scale score, hematoma volume, presence or absence of intraventricular hemorrhage, hyperlipidemia, cigarette smoking, and hypertension (no interaction between hyperglycemia and preexisting diabetes, P=0.996). Among the patients without preexisting diabetes, both moderate (odds ratio, 1.8 [95% CI, 1.0-3.2]) and severe (odds ratio, 2.0 [95% CI, 1.1-3.7]) hyperglycemia were associated with 90-day death or disability after adjusting for above mentioned potential confounders. Among the patients with preexisting diabetes, moderate and severe hyperglycemia were not associated with 90-day death or disability. CONCLUSIONS: Persistent hyperglycemia, either moderate or severe, increased the risk of death or disability in nondiabetic patients with intracerebral hemorrhage. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01176565.

Intracerebral Hemorrhage and Coronavirus Disease 2019 in a Cohort of 282,718 Hospitalized Patients.

BACKGROUND: To identify whether the risk of intracerebral hemorrhage is higher in patients with coronavirus disease 2019 (COVID-19), we compared the risk factors, comorbidities, and outcomes in patients intracerebral hemorrhage and COVID-19 and those without COVID-19. METHODS: We analyzed the data from the Cerner deidentified COVID-19 data set derived from 62 health care facilities. The data set included patients with an emergency department or inpatient encounter with discharge diagnoses codes that could be associated with suspicion of or exposure to COVID-19 or confirmed COVID-19. RESULTS: There were a total of 154 (0.2%) and 667 (0.3%) patients with intracerebral hemorrhage among 85,645 patients with COVID-19 and 197,073 patients without COVID-19, respectively. In the multivariate model, there was a lower risk of intracerebral hemorrhage in patients with COVID-19 (odds ratio 0.5; 95% confidence interval 0.5-0.6; p < .0001) after adjustment for sex, age strata, race/ethnicity, hypertension, diabetes mellitus, nicotine dependence/tobacco use, hyperlipidemia, atrial fibrillation, congestive heart failure, long-term anticoagulant use, and alcohol abuse. The proportions of patients who developed pneumonia (58.4% versus 22.5%; p < .0001), acute kidney injury (48.7% versus 31.0%; p < .0001), acute myocardial infarction (11% versus 6.4%; p = .048), sepsis (41.6% versus 22.5%; p < .0001), and respiratory failure (61.7% versus 42.3%; p < .0001) were significantly higher among patients with intracerebral hemorrhage and COVID-19 compared with those without COVID-19. The in-hospital mortality among patients with intracerebral hemorrhage and COVID-19 was significantly higher compared with that among those without COVID-19 (40.3% versus 19.0%; p < .0001). CONCLUSIONS: Our analysis does not suggest that rates of intracerebral hemorrhage are higher in patients with COVID-19. The higher mortality in patients with intracerebral hemorrhage and COVID-19 compared with those without COVID-19 is likely mediated by higher frequency of comorbidities and adverse in-hospital events.

Lessons Learned from Phase II and Phase III Trials Investigating Therapeutic Agents for Cerebral Ischemia Associated with Aneurysmal Subarachnoid Hemorrhage.

One of the challenges in bringing new therapeutic agents (since nimodipine) in for the treatment of cerebral ischemia associated with aneurysmal subarachnoid hemorrhage (aSAH) is the incongruence in therapeutic benefit observed between phase II and subsequent phase III clinical trials. Therefore, identifying areas for improvement in the methodology and interpretation of results is necessary to increase the value of phase II trials. We performed a systematic review of phase II trials that continued into phase III trials, evaluating a therapeutic agent for the treatment of cerebral ischemia associated with aSAH. We followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines for systematic reviews, and review was based on a peer-reviewed protocol (International Prospective Register of Systematic Reviews no. 222965). A total of nine phase III trials involving 7,088 patients were performed based on eight phase II trials involving 1558 patients. The following therapeutic agents were evaluated in the selected phase II and phase III trials: intravenous tirilazad, intravenous nicardipine, intravenous clazosentan, intravenous magnesium, oral statins, and intraventricular nimodipine. Shortcomings in several design elements of the phase II aSAH trials were identified that may explain the incongruence between phase II and phase III trial results. We suggest the consideration of the following strategies to improve phase II design: increased focus on the selection of surrogate markers of efficacy, selection of the optimal dose and timing of intervention, adjustment for exaggerated estimate of treatment effect in sample size calculations, use of prespecified go/no-go criteria using futility design, use of multicenter design, enrichment of the study population, use of concurrent control or placebo group, and use of innovative trial designs such as seamless phase II to III design. Modifying the design of phase II trials on the basis of lessons learned from previous phase II and phase III trial combinations is necessary to plan more effective phase III trials.

COVID-19 Exposure During Neurology Practice: Results of American Academy of Neurology Survey.

BACKGROUND: To determine the exposure risk for coronavirus 2019 (COVID-19) during neurology practice. Neurological manifestations of COVID-19 are increasingly being recognized mandating high level of participation by neurologists. METHODS: An American Academy of Neurology survey inquiring about various aspects of COVID-19 exposure was sent to a random sample of 800 active American Academy of Neurology members who work in the United States. Use of second tier protection (1 or more including sterile gloves, surgical gown, protective goggles/face shield but not N95 mask) or maximum protection (N95 mask in addition to second tier protection) during clinical encounter with suspected/confirmed COVID-19 patients was inquired. RESULTS: Of the 81 respondents, 38% indicated exposure to COVID-19 at work, 1% at home, and none outside of work/home. Of the 28 respondents who did experience at least 1 symptom of COVID-19, tiredness (32%) or diarrhea (8%) were reported. One respondent tested positive out of 12 (17%) of respondents who were tested for COVID-19 within the last 2 weeks. One respondent received health care at an emergency department/urgent care or was hospitalized related to COVID-19. When seeing patients, maximum protection personal protective equipment was used either always or most of the times by 16% of respondents in outpatient setting and 56% of respondents in inpatient settings, respectively. CONCLUSIONS: The data could enhance our knowledge of the factors that contribute to COVID-19 exposure during neurology practice in United States, and inform education and advocacy efforts to neurology providers, trainees, and patients in this unprecedented pandemic.

Repeat Revascularization over 10 Years Following Carotid Endarterectomy or Carotid Stent Placement: An Analysis of Carotid Revascularization Endarterectomy Versus Stenting Trial.

OBJECTIVE: To identify rates of and factors associated with repeat revascularization in a large cohort of patients prospectively followed over 10 years in Carotid Revascularization Endarterectomy versus Stenting Trial. METHODS: We compared the effect of carotid angioplasty and stenting (CAS) versus carotid endarterectomy (CEA) on risk of repeat revascularization after adjusting for age, sex, symptomatic status, and initial severity of stenosis (≥70% vs. <70%) using Cox proportional hazards analysis. We used Kaplan-Meier analysis to assess repeat revascularization-free survival for the overall cohort. RESULTS: Repeat revascularization was performed in 90 (3.9%, 95% confidence interval [CI] 3.1%-4.8%) of 2318 patients; 6 (6.7%, 95% CI 2.5%-14.0%) patients experienced the composite end point of any stroke, myocardial infarction, or death within 30 days after repeat revascularization. There was no difference in risk of repeat revascularization in patients who underwent CAS (compared with CEA) as the index procedure (hazard ratio 0.92, 95% CI 0.69-1.23, P = 0.5765). Patient's age (hazard ratio 1.01, 95% CI 1.01-1.02, P < 0.0001) was associated with performance of repeat revascularization. Mean ± SD repeat revascularization-free survival was 8.2 ± 0.1 years and 8.0 ± 0.1 years for CAS and CEA, respectively (log-rank test P = 0.0823). CONCLUSIONS: A low rate of repeat revascularization was seen without any significant difference among patients who underwent CEA or CAS over 10 years. The 6.7% rate of composite end point within 30 days after procedure highlights the need for standardizing the indications for repeat revascularization.

Intra-arterial injection of lidocaine into middle meningeal artery to treat intractable headaches and severe migraine.

BACKGROUND AND PURPOSE: We report the results of intra-arterial injection of lidocaine in the middle meningeal artery in patients with intractable headache or status migrainosus. METHODS: We treated four patients with intra-arterial lidocaine (2 mg/ml) in doses up to 50 mg in each middle meningeal artery via a microcatheter bilaterally (except in one patient). In two patients with intractable headache, the daily maximum intensity of headache (graded by 11-point numeric rating scale) was recorded for 7 days postprocedure. In two patients with status migrainosus, migraine-related disability 3 months prior and after treatment using MIDAS (Migraine Disability Assessment) questionnaire was recorded. RESULTS: Intra-arterial lidocaine reduced the headache intensity from 8/10 and 10/10 to 0/10 in the two patients with intractable headaches for 2 days (day 0 and day 1) postprocedure. Despite recurrence of headache on day 2, the intensity was less than preprocedure intensity up to the last day recorded (by 3 and 2 points on day 7). In the two patients with status migrainosus, there was immediate reduction in headache intensity following intra-arterial lidocaine. The post treatment 3-month MIDAS score was lower in both patients compared with pretreatment 3-month score; 3 versus 30 and 55 versus 90. Severe disability preprocedure by MIDAS was reduced to little or no disability postprocedure in one patient. CONCLUSIONS: Intra-arterial lidocaine resulted in amelioration of headache in patients with intractable headache and those with status migrainosus with improvement lasting longer than the short half-life of lidocaine possibly related to central desensitization.

Effect of Race and Ethnicity on In-Hospital Mortality in Patients with COVID-19.

Objective: To identify differences in short-term outcomes of patients with coronavirus disease 2019 (COVID-19) according to various racial/ethnic groups. Design: Analysis of Cerner de-identified COVID-19 dataset. Setting: A total of 62 health care facilities. Participants: The cohort included 49,277 adult COVID-19 patients who were hospitalized from December 1, 2019 to November 13, 2020. Main Outcome Measures: The primary outcome of interest was in-hospital mortality. The secondary outcome was non-routine discharge (discharge to destinations other than home, such as short-term hospitals or other facilities including intermediate care and skilled nursing homes). Methods: We compared patients' age, gender, individual components of Charlson and Elixhauser comorbidities, medical complications, use of do-not-resuscitate, use of palliative care, and socioeconomic status between various racial and/or ethnic groups. We further compared the rates of in-hospital mortality and non-routine discharges between various racial and/or ethnic groups. Results: Compared with White patients, in-hospital mortality was significantly higher among African American (OR 1.5; 95%CI:1.3-1.6, P<.001), Hispanic (OR1.4; 95%CI:1.3-1.6, P<.001), and Asian or Pacific Islander (OR 1.5; 95%CI: 1.1-1.9, P=.002) patients after adjustment for age and gender, Elixhauser comorbidities, do-not-resuscitate status, palliative care use, and socioeconomic status. Conclusions: Our study found that, among hospitalized patients with COVID-2019, African American, Hispanic, and Asian or Pacific Islander patients had increased mortality compared with White patients after adjusting for sociodemographic factors, comorbidities, and do-not-resuscitate/palliative care status. Our findings add additional perspective to other recent studies.

Subarachnoid Hemorrhage and COVID-19: An Analysis of 282,718 Patients.

BACKGROUND: Intracranial hemorrhage (including subarachnoid hemorrhage [SAH]) has been reported in 0.3%-1.2% of patients with coronavirus disease 2019 (COVID-19). However, no study has evaluated the risk of SAH in patients with COVID-19. METHODS: We analyzed data from 62 health care facilities using the Cerner de-identified COVID-19 dataset. RESULTS: There were 86 (0.1%) and 376 (0.2%) patients with SAH among 85,645 patients with COVID-19 and 197,073 patients without COVID-19, respectively. In the multivariate model, there was a lower risk of SAH in patients with COVID-19 (odds ratio 0.5, 95% confidence interval 0.4-0.7, P < 0.0001) after adjusting for sex, age strata, race/ethnicity, hypertension, and nicotine dependence/tobacco use. The proportions of patients who developed pneumonia (58.1% vs. 21.3%, P < 0.0001), acute kidney injury (43% vs. 27.7%, P = 0.0005), septic shock (44.2% vs. 20.7%, P < 0.0001), and respiratory failure (64.0% vs. 39.1%, P < 0.0001) were significantly higher among patients with SAH and COVID-19 compared with patients without COVID-19. The in-hospital mortality among patients with SAH and COVID-19 was significantly higher compared with patients without COVID-19 (31.4% vs. 12.2%, P < 0.0001). CONCLUSIONS: The risk of SAH was not increased in patients with COVID-19. The higher mortality in patients with SAH and COVID-19 compared with patients without COVID-19 is likely mediated by higher frequency of systemic comorbidities.

Acute Ischemic Stroke and COVID-19: An Analysis of 27 676 Patients.

BACKGROUND AND PURPOSE: Acute ischemic stroke may occur in patients with coronavirus disease 2019 (COVID-19), but risk factors, in-hospital events, and outcomes are not well studied in large cohorts. We identified risk factors, comorbidities, and outcomes in patients with COVID-19 with or without acute ischemic stroke and compared with patients without COVID-19 and acute ischemic stroke. METHODS: We analyzed the data from 54 health care facilities using the Cerner deidentified COVID-19 dataset. The dataset included patients with an emergency department or inpatient encounter with discharge diagnoses codes that could be associated to suspicion of or exposure to COVID-19 or confirmed COVID-19. RESULTS: A total of 103 (1.3%) patients developed acute ischemic stroke among 8163 patients with COVID-19. Among all patients with COVID-19, the proportion of patients with hypertension, diabetes, hyperlipidemia, atrial fibrillation, and congestive heart failure was significantly higher among those with acute ischemic stroke. Acute ischemic stroke was associated with discharge to destination other than home or death (relative risk, 2.1 [95% CI, 1.6-2.4]; P<0.0001) after adjusting for potential confounders. A total of 199 (1.0%) patients developed acute ischemic stroke among 19 513 patients without COVID-19. Among all ischemic stroke patients, COVID-19 was associated with discharge to destination other than home or death (relative risk, 1.2 [95% CI, 1.0-1.3]; P=0.03) after adjusting for potential confounders. CONCLUSIONS: Acute ischemic stroke was infrequent in patients with COVID-19 and usually occurs in the presence of other cardiovascular risk factors. The risk of discharge to destination other than home or death increased 2-fold with occurrence of acute ischemic stroke in patients with COVID-19.

Changes in Neuroendovascular Procedural Volume During the COVID-19 Pandemic: An International Multicenter Study.

BACKGROUND AND PURPOSE: The effect of coronavirus disease 2019 (COVID-19) pandemic on performance of neuroendovascular procedures has not been quantified. METHODS: We performed an audit of performance of neuroendovascular procedures at 18 institutions (seven countries) for two periods; January-April 2019 and 2020, to identify changes in various core procedures. We divided the region where the hospital was located based on the median value of total number of COVID-19 cases per 100,00 population-into high and low prevalent regions. RESULTS: Between 2019 and 2020, there was a reduction in number of cerebral angiograms (30.9% reduction), mechanical thrombectomy (8% reduction), carotid artery stent placement for symptomatic (22.7% reduction) and asymptomatic (43.4% reduction) stenoses, intracranial angioplasty and/or stent placement (45% reduction), and endovascular treatment of unruptured intracranial aneurysms (44.6% reduction) and ruptured (22.9% reduction) and unruptured brain arteriovenous malformations (66.4% reduction). There was an increase in the treatment of ruptured intracranial aneurysms (10% increase) and other neuroendovascular procedures (34.9% increase). There was no relationship between procedural volume change and intuitional location in high or low COVID-19 prevalent regions. The procedural volume reduction was mainly observed in March-April 2020. CONCLUSIONS: We provided an international multicenter view of changes in neuroendovascular practices to better understand the gaps in provision of care and identify individual procedures, which are susceptible to change.

Intraprocedural Back Pain Associated with Awake Neuroendovascular Procedures.

BACKGROUND AND PURPOSE: The prevalence and characteristics of intraprocedural back pain is not well studied in awake patients undergoing neuroendovascular procedures. METHODS: We performed a prospective study as part of quality improvement initiative in which all patients who underwent neuroendovascular procedures in awake state were inquired regarding presence, severity (using a numeric rating scale score ranging from 0 [no pain] to 10 [worst pain possible]), and location (using anatomical chart) of back pain immediately after the procedure. The primary endpoint was the proportion of patients with moderate to severe pain (score of ≥3). RESULTS: A total of 100 (41.3%) of 242 patients reported intraprocedural back pain with a median severity of 5/10 (range 1-10). The mean age was 58.7 ± 16.2 years. The mean duration of the procedure was 82.3 minutes (range 15-410 minutes). The pain was classified as moderate to severe in 86 of 100 patients. The locations of pain were identified in lumbar (n = 77), thoracic (n = 6), cervical (n = 7), cervical and lumbar (n = 8), and cervical with thoracolumbar (n = 2) regions. There was a significant relationship between patients' history of the previous neck and/or back surgery and frequency of moderate to severe back pain (P = .02). No significant relationship was observed between frequency of none to mild and moderate to severe back pain among the strata by patients' age, body mass index, or duration of procedures. CONCLUSIONS: The relatively high prevalence of intraprocedural back pain in patients undergoing neuroendovascular procedures in awake state must be recognized, and strategies to reduce the occurrence need to be identified.

Mandated societal lockdown and road traffic accidents.

BACKGROUND: The effect of mandated societal lockdown to reduce the transmission of coronavirus disease 2019 (COVID-19) on road traffic accidents is not known. For this reason, we performed an in-depth analysis using data from Statewide Traffic Accident Records System. MATERIALS AND METHODS: We reviewed data on total 2292 road traffic accident records in Missouri from January 1, 2020 through May 15, 2020. We treated March 23 as the first day of mandated societal lockdown and May 3 as the first day of re-opening. RESULTS: We have found that there was a significant reduction in road traffic accidents resulting in minor or no injuries (mean 14.5 versus 10.8, p < 0.0001) but not in accidents resulting in serious or fatal injuries (mean 3.4 versus 3.7, p = 0.42) after mandated societal lockdown. Furthermore, there was a significant reduction in road traffic accidents resulting in minor or no injuries after the mandated social lockdown (parameter estimate -5.9, p = 0.0028) in the time series analysis. There was an increase in road traffic accidents resulting in minor or no injuries after expiration of mandatory societal lockdown (mean 10.8 versus 13.7, p = 0.04). CONCLUSION: The mandated societal lockdown policies led to reduction in road traffic accidents resulting in non-serious or no injuries but not those resulting in serious or fatal injuries.

Outcomes of Intensive Systolic Blood Pressure Reduction in Patients With Intracerebral Hemorrhage and Excessively High Initial Systolic Blood Pressure: Post Hoc Analysis of a Randomized Clinical Trial.

Importance: The safety and efficacy of intensive systolic blood pressure reduction in patients with intracerebral hemorrhage who present with systolic blood pressure greater than 220 mm Hg appears to be unknown. Objective: To evaluate the differential outcomes of intensive (goal, 110-139 mm Hg) vs standard (goal, 140-179 mm Hg) systolic blood pressure reduction in patients with intracerebral hemorrhage and initial systolic blood pressure of 220 mm Hg or more vs less than 220 mm Hg. Design, Setting, and Participants: This post hoc analysis of the Antihypertensive Treatment of Acute Cerebral Hemorrhage-II trial was performed in November 2019 on data from the multicenter randomized clinical trial, which was conducted between May 2011 to September 2015. Patients with intracerebral hemorrhage and initial systolic blood pressure of 180 mm Hg or more, randomized within 4.5 hours after symptom onset, were included. Interventions: Intravenous nicardipine infusion titrated to goals. Main Outcomes and Measures: Neurological deterioration and hematoma expansion within 24 hours and death or severe disability at 90 days, plus kidney adverse events and serious adverse events until day 7 or hospital discharge. Results: A total of 8532 patients were screened, and 999 individuals (mean [SD] age, 62.0 [13.1] years; 620 men [62.0%]) underwent randomization and had an initial SBP value. Among 228 participants with initial systolic blood pressures of 220 mm Hg or more, the rate of neurological deterioration within 24 hours was higher in those who underwent intensive (vs standard) systolic blood pressure reduction (15.5% vs 6.8%; relative risk, 2.28 [95% CI, 1.03-5.07]; P = .04). The rate of death and severe disability (39.0% vs 38.4%; relative risk, 1.02 [95% CI, 0.73-1.78]; P = .92) was not significantly different between the 2 groups. There was a significantly higher rate of kidney adverse events in participants randomized to intensive systolic blood pressure reduction (13.6% vs 4.2%; relative risk, 3.22 [95% CI, 1.21-8.56]; P = .01), but no difference was observed in the rate of kidney serious adverse events. Conclusions and Relevance: The higher rate of neurological deterioration within 24 hours associated with intensive treatment in patients with intracerebral hemorrhage and initial systolic blood pressure of 220 mm Hg or more, without any benefit in reducing hematoma expansion at 24 hours or death or severe disability at 90 days, warrants caution against generalization of recommendations for intensive systolic blood pressure reduction.

Systolic Blood Pressure Reduction and Acute Kidney Injury in Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: We determined the rates and predictors of acute kidney injury (AKI) and renal adverse events (AEs), and effects of AKI and renal AEs on death or disability in patients with intracerebral hemorrhage. METHODS: We analyzed data from a multicenter trial which randomized 1000 intracerebral hemorrhage patients with initial systolic blood pressure ≥180 mm Hg to intensive (goal 110-139 mm Hg) over standard (goal 140-179 mm Hg) systolic blood pressure reduction within 4.5 hours of symptom onset. AKI was identified by serial assessment of daily serum creatinine for 3 days post randomization. RESULTS: AKI and renal AEs were observed in 149 patients (14.9%) and 65 patients (6.5%) among 1000 patients, respectively. In multivariate analysis, the higher baseline serum creatinine (≥110 µmol/L) was associated with AKI (odds ratio 2.4 [95% CI, 1.2-4.5]) and renal AEs (odds ratio 3.1 [95% CI, 1.2-8.1]). Higher area under the curve for intravenous nicardipine dose was associated with AKI (odds ratio 1.003 [95% CI, 1.001-1.005]) and renal AEs (odds ratio 1.003 [95% CI, 1.001-1.006]). There was a higher risk to death (relative risk 2.6 [95% CI, 1.6-4.2]) and death or disability (relative risk 1.5 [95% CI, 1.3-1.8]) at 90 days in patients with AKI but not in those with renal AEs. CONCLUSIONS: Intracerebral hemorrhage patients with higher baseline serum creatinine and those receiving higher doses of nicardipine were at higher risk for AKI and renal AEs. Occurrence of AKI was associated higher rates of death or disability at 3 months. Registration: URL: https://clinicaltrials.gov. Unique identifier: NCT01176565.

The Stenting versus Aggressive Medical Therapy for Intracranial Arterial Stenosis Trial: Reanalysis Using the FDA "On Label" Criteria.

BACKGROUND AND PURPOSE: Due to higher rates of 1-month stroke and death with Wingspan intracranial stent placement observed in SAMMPRIS, the Food and Drug Administration (FDA) announced a more limited indication for Wingspan stent. METHODS: We compared the results of intracranial stent placement with best medical treatment in patients recruited in SAMMPRIS who met the new "on label" criteria with those who were categorized as "off label." The primary endpoint was any stroke or death occurring within 30 days of enrollment, or an ischemic stroke in the territory of the symptomatic intracranial artery from day 31 after study entry to completion of follow-up. RESULTS: A total of 31 (7%) among 451 recruited patients met the "on label" criteria. The relative risk of primary endpoint was lower in "on label" patients treated with stent placement compared with best medical treatment (relative risk .61, 95% confidence interval .2-1.7) but higher in "off label" patients (relative risk 1.81, 95% confidence interval 1.2-2.6). Primary endpoint was seen in 20% and 23.4% of patients treated with stent placement in "on label" and "off label" patients, respectively. Primary endpoint was seen in 25% and 14.2% of patients treated with best medical treatment in "on label" and "off label" patients, respectively. CONCLUSION: The new FDA "on label" criteria may identify a small group of people, who may benefit from intracranial stent placement due to higher risk of primary endpoint in those treated with best medical treatment.

Acute Kidney Injury in Acute Ischemic Stroke Patients in Clinical Trials.

OBJECTIVES: Acute ischemic stroke patients are at risk of acute kidney injury due to volume depletion, contrast exposure, and preexisting comorbid diseases. We determined the occurrence rate and identified predictors associated with acute kidney injury in acute ischemic stroke patients. SETTING: Multiple specialized ICUs within academic medical centers. DESIGN: Post hoc analysis of pooled data from prospective randomized clinical trials. PATIENTS: Acute ischemic stroke patients recruited within 3 hours or within 5 hours of symptom onset. INTERVENTIONS: IV recombinant tissue plasminogen activator, endovascular treatment, IV albumin, or placebo. MEASUREMENTS AND MAIN RESULTS: Serum creatinine levels from baseline and within day 5 or discharge were used to classify acute kidney injury classification into stages. Any increase in serum creatinine was seen in 697 (36.1%) and acute kidney injury was seen in 68 (3.5%) of 1,931 patients with acute ischemic stroke. Severity of acute kidney injury was grade I, II, and III in 3.1%, 0.4%, and 0.05% patients, respectively. Patients with albumin (5.5% compared with 2.6%; p = 0.001), preexisting hypertension (4.3% compared with 1.5%; p = 0.0041), and preexisting renal disease (9.1% compared with 3.0%; p < 0.0001) had higher risk of acute kidney injury. The risk of acute kidney injury was lower between those who either underwent CT angiography (2.0% compared with 4.7%; p = 0.0017) or endovascular treatment (1.6% compared with 4.2%; p = 0.0071). In the multivariate analysis, hypertension (odds ratio, 2.6; 95% CI, 1.2-5.6) and renal disease (odds ratio, 3.5; 95% CI, 1.9-6.5) were associated with acute kidney injury. The risk of death was significantly higher among patients with acute kidney injury (odds ratio, 2.7; 95% CI, 1.4-4.9) after adjusting for age and National Institutes of Health Stroke Scale score strata. CONCLUSIONS: The occurrence rate of acute kidney injury in acute ischemic stroke patients was low and was not higher in patients who underwent CT angiogram or those who received endovascular treatment. Occurrence of acute kidney injury increased the risk of death within 3 months among acute ischemic stroke patients.