Tenecteplase for Stroke at 4.5 to 24 Hours with Perfusion-Imaging Selection.

BACKGROUND: Thrombolytic agents, including tenecteplase, are generally used within 4.5 hours after the onset of stroke symptoms. Information on whether tenecteplase confers benefit beyond 4.5 hours is limited. METHODS: We conducted a multicenter, double-blind, randomized, placebo-controlled trial involving patients with ischemic stroke to compare tenecteplase (0.25 mg per kilogram of body weight, up to 25 mg) with placebo administered 4.5 to 24 hours after the time that the patient was last known to be well. Patients had to have evidence of occlusion of the middle cerebral artery or internal carotid artery and salvageable tissue as determined on perfusion imaging. The primary outcome was the ordinal score on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability and a score of 6 indicating death) at day 90. Safety outcomes included death and symptomatic intracranial hemorrhage. RESULTS: The trial enrolled 458 patients, 77.3% of whom subsequently underwent thrombectomy; 228 patients were assigned to receive tenecteplase, and 230 to receive placebo. The median time between the time the patient was last known to be well and randomization was approximately 12 hours in the tenecteplase group and approximately 13 hours in the placebo group. The median score on the modified Rankin scale at 90 days was 3 in each group. The adjusted common odds ratio for the distribution of scores on the modified Rankin scale at 90 days for tenecteplase as compared with placebo was 1.13 (95% confidence interval, 0.82 to 1.57; P = 0.45). In the safety population, mortality at 90 days was 19.7% in the tenecteplase group and 18.2% in the placebo group, and the incidence of symptomatic intracranial hemorrhage was 3.2% and 2.3%, respectively. CONCLUSIONS: Tenecteplase therapy that was initiated 4.5 to 24 hours after stroke onset in patients with occlusions of the middle cerebral artery or internal carotid artery, most of whom had undergone endovascular thrombectomy, did not result in better clinical outcomes than those with placebo. The incidence of symptomatic intracerebral hemorrhage was similar in the two groups. (Funded by Genentech; TIMELESS ClinicalTrials.gov number, NCT03785678.).

Tenecteplase for Ischemic Stroke at 4.5 to 24 Hours without Thrombectomy.

BACKGROUND: Tenecteplase is an effective thrombolytic agent for eligible patients with stroke who are treated within 4.5 hours after the onset of stroke. However, data regarding the effectiveness of tenecteplase beyond 4.5 hours are limited. METHODS: In a trial conducted in China, we randomly assigned patients with large-vessel occlusion of the middle cerebral artery or internal carotid artery who had salvageable brain tissue as identified on perfusion imaging and who did not have access to endovascular thrombectomy to receive tenecteplase (at a dose of 0.25 mg per kilogram of body weight; maximum dose, 25 mg) or standard medical treatment within 4.5 to 24 hours after the time that the patient was last known to be well (including after stroke on awakening and unwitnessed stroke). The primary outcome was the absence of disability, which was defined as a score of 0 or 1 on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability), at day 90. The key safety outcomes were symptomatic intracranial hemorrhage and death. RESULTS: A total of 516 patients were enrolled; 264 were randomly assigned to receive tenecteplase and 252 to receive standard medical treatment. Less than 2% of the patients (4 in the tenecteplase group and 5 in the standard-treatment group) underwent rescue endovascular thrombectomy. Treatment with tenecteplase resulted in a higher percentage of patients with a modified Rankin scale score of 0 or 1 at 90 days than standard medical treatment (33.0% vs. 24.2%; relative rate, 1.37; 95% confidence interval, 1.04 to 1.81; P = 0.03). Mortality at 90 days was 13.3% with tenecteplase and 13.1% with standard medical treatment, and the incidence of symptomatic intracranial hemorrhage within 36 hours after treatment was 3.0% and 0.8%, respectively. CONCLUSIONS: In this trial involving Chinese patients with ischemic stroke due to large-vessel occlusion, most of whom did not undergo endovascular thrombectomy, treatment with tenecteplase administered within 4.5 to 24 hours after stroke onset resulted in less disability and similar survival as compared with standard medical treatment, and the incidence of symptomatic intracranial hemorrhage appeared to be higher. (Funded by the National Natural Science Foundation of China and others; TRACE-III ClinicalTrials.gov number, NCT05141305.).

Shorter Door-to-Needle Times Are Associated With Better Outcomes After Intravenous Thrombolytic Therapy and Endovascular Thrombectomy for Acute Ischemic Stroke.

BACKGROUND: Existing data and clinical trials could not determine whether faster intravenous thrombolytic therapy (IVT) translates into better long-term functional outcomes after acute ischemic stroke among those treated with endovascular thrombectomy (EVT). Patient-level national data can provide the required large population to study the associations between earlier IVT, versus later, with longitudinal functional outcomes and mortality in patients receiving IVT+EVT combined treatment. METHODS: This cohort study included older US patients (age ≥65 years) who received IVT within 4.5 hours or EVT within 7 hours after acute ischemic stroke using the linked 2015 to 2018 Get With The Guidelines-Stroke and Medicare database (38 913 treated with IVT only and 3946 with IVT+EVT). Primary outcome was home time, a patient-prioritized functional outcome. Secondary outcomes included all-cause mortality in 1 year. Multivariate logistic regression and Cox proportional hazards models were used to evaluate the associations between door-to-needle (DTN) times and outcomes. RESULTS: Among patients treated with IVT+EVT, after adjusting for patient and hospital factors, including onset-to-EVT times, each 15-minute increase in DTN times for IVT was associated with significantly higher odds of zero home time in a year (never discharged to home) (adjusted odds ratio, 1.12 [95% CI, 1.06-1.19]), less home time among those discharged to home (adjusted odds ratio, 0.93 per 1% of 365 days [95% CI, 0.89-0.98]), and higher all-cause mortality (adjusted hazard ratio, 1.07 [95% CI, 1.02-1.11]). These associations were also statistically significant among patients treated with IVT but at a modest degree (adjusted odds ratio, 1.04 for zero home time, 0.96 per 1% home time for those discharged to home, and adjusted hazard ratio 1.03 for mortality). In the secondary analysis where the IVT+EVT group was compared with 3704 patients treated with EVT only, shorter DTN times (≤60, 45, and 30 minutes) achieved incrementally more home time in a year, and more modified Rankin Scale 0 to 2 at discharge (22.3%, 23.4%, and 25.0%, respectively) versus EVT only (16.4%, P<0.001 for each). The benefit dissipated with DTN>60 minutes. CONCLUSIONS: Among older patients with stroke treated with either IVT only or IVT+EVT, shorter DTN times are associated with better long-term functional outcomes and lower mortality. These findings support further efforts to accelerate thrombolytic administration in all eligible patients, including EVT candidates.

Twenty Years of Get With The Guidelines-Stroke: Celebrating Past Successes, Lessons Learned, and Future Challenges.

The Get With The Guidelines-Stroke program which, began 20 years ago, is one of the largest and most important nationally representative disease registries in the United States. Its importance to the stroke community can be gauged by its sustained growth and widespread dissemination of findings that demonstrate sustained increases in both the quality of care and patient outcomes over time. The objectives of this narrative review are to provide a brief history of Get With The Guidelines-Stroke, summarize its major successes and impact, and highlight lessons learned. Looking to the next 20 years, we discuss potential challenges and opportunities for the program.

Thrombolysis for Wake-Up Stroke Versus Non-Wake-Up Unwitnessed Stroke: EOS Individual Patient Data Meta-Analysis.

BACKGROUND: Stroke with unknown time of onset can be categorized into 2 groups; wake-up stroke (WUS) and unwitnessed stroke with an onset time unavailable for reasons other than wake-up (non-wake-up unwitnessed stroke, non-WUS). We aimed to assess potential differences in the efficacy and safety of intravenous thrombolysis (IVT) between these subgroups. METHODS: Patients with an unknown-onset stroke were evaluated using individual patient-level data of 2 randomized controlled trials (WAKE-UP [Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke], THAWS [Thrombolysis for Acute Wake-Up and Unclear-Onset Strokes With Alteplase at 0.6 mg/kg]) comparing IVT with placebo or standard treatment from the EOS (Evaluation of Unknown-Onset Stroke Thrombolysis trial) data set. A favorable outcome was prespecified as a modified Rankin Scale score of 0 to 1 at 90 days. Safety outcomes included symptomatic intracranial hemorrhage at 22 to 36 hours and 90-day mortality. The IVT effect was compared between the treatment groups in the WUS and non-WUS with multivariable logistic regression analysis. RESULTS: Six hundred thirty-four patients from 2 trials were analyzed; 542 had WUS (191 women, 272 receiving alteplase), and 92 had non-WUS (42 women, 43 receiving alteplase). Overall, no significant interaction was noted between the mode of onset and treatment effect (P value for interaction=0.796). In patients with WUS, the frequencies of favorable outcomes were 54.8% and 45.5% in the IVT and control groups, respectively (adjusted odds ratio, 1.47 [95% CI, 1.01-2.16]). Death occurred in 4.0% and 1.9%, respectively (P=0.162), and symptomatic intracranial hemorrhage in 1.8% and 0.3%, respectively (P=0.194). In patients with non-WUS, no significant difference was observed in favorable outcomes relative to the control (37.2% versus 29.2%; adjusted odds ratio, 1.76 [0.58-5.37]). One death and one symptomatic intracranial hemorrhage were reported in the IVT group, but none in the control. CONCLUSIONS: There was no difference in the effect of IVT between patients with WUS and non-WUS. IVT showed a significant benefit in patients with WUS, while there was insufficient statistical power to detect a substantial benefit in the non-WUS subgroup. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: CRD42020166903.

Mapping the Ecological Terrain of Stroke Prehospital Delay: A Nationwide Registry Study.

BACKGROUND: Delays in hospital presentation limit access to acute stroke treatments. While prior research has focused on patient-level factors, broader ecological and social determinants have not been well studied. We aimed to create a geospatial map of prehospital delay and examine the role of community-level social vulnerability. METHODS: We studied patients with ischemic stroke who arrived by emergency medical services in 2015 to 2017 from the American Heart Association Get With The Guidelines-Stroke registry. The primary outcome was time to hospital arrival after stroke (in minutes), beginning at last known well in most cases. Using Geographic Information System mapping, we displayed the geography of delay. We then used Cox proportional hazard models to study the relationship between community-level factors and arrival time (adjusted hazard ratios [aHR] <1.0 indicate delay). The primary exposure was the social vulnerability index (SVI), a metric of social vulnerability for every ZIP Code Tabulation Area ranging from 0.0 to 1.0. RESULTS: Of 750 336 patients, 149 145 met inclusion criteria. The mean age was 73 years, and 51% were female. The median time to hospital arrival was 140 minutes (Q1: 60 minutes, Q3: 458 minutes). The geospatial map revealed that many zones of delay overlapped with socially vulnerable areas (https://harvard-cga.maps.arcgis.com/apps/webappviewer/index.html?id=08f6e885c71b457f83cefc71013bcaa7). Cox models (aHR, 95% CI) confirmed that higher SVI, including quartiles 3 (aHR, 0.96 [95% CI, 0.93-0.98]) and 4 (aHR, 0.93 [95% CI, 0.91-0.95]), was associated with delay. Patients from SVI quartile 4 neighborhoods arrived 15.6 minutes [15-16.2] slower than patients from SVI quartile 1. Specific SVI themes associated with delay were a community's socioeconomic status (aHR, 0.80 [95% CI, 0.74-0.85]) and housing type and transportation (aHR, 0.89 [95% CI, 0.84-0.94]). CONCLUSIONS: This map of acute stroke presentation times shows areas with a high incidence of delay. Increased social vulnerability characterizes these areas. Such places should be systematically targeted to improve population-level stroke presentation times.

Tenecteplase versus alteplase in acute ischaemic cerebrovascular events (TRACE-2): a phase 3, multicentre, open-label, randomised controlled, non-inferiority trial.

BACKGROUND: There is increasing interest in replacing alteplase with tenecteplase as the preferred thrombolytic treatment for patients with acute ischaemic stroke. We aimed to establish the non-inferiority of tenecteplase to alteplase for these patients. METHODS: In this multicentre, prospective, open-label, blinded-endpoint, randomised controlled, non-inferiority trial, adults with an acute ischaemic stroke who were eligible for standard intravenous thrombolysis but ineligible for endovascular thrombectomy were enrolled from 53 centres in China and randomly assigned (1:1) to receive intravenous tenecteplase (0·25 mg/kg, maximum dose of 25 mg) or intravenous alteplase (0·9 mg/kg, maximum dose of 90 mg). Participants had to be able to receive treatment within 4·5 h of stroke, have a modified Rankin Scale (mRS) score of no more than 1 before enrolment, and have a National Institutes of Health Stroke Scale score of 5-25. Patients and treating clinicians were not masked to group assignment; clinicians evaluating outcomes were masked to treatment type. The primary efficacy outcome was the proportion of participants who had a mRS score of 0-1 at 90 days, assessed in the modified intention-to-treat population (all randomly assigned participants who received the allocated thrombolytic), with a non-inferiority margin of 0·937 for the risk ratio (RR). The primary safety outcome was symptomatic intracranial haemorrhage within 36 h, assessed in all participants who received study drug and had a safety assessment available. The trial is registered with ClinicalTrials.gov, NCT04797013, and has been completed. FINDINGS: Between June 12, 2021, and May 29, 2022, 1430 participants were enrolled and randomly assigned to tenecteplase (n=716) or alteplase (n=714). Six patients assigned to tenecteplase and seven to alteplase did not receive study product, and five participants in the tenecteplase group and 11 in the alteplase group were lost to follow-up at 90 days. The primary outcome in the modified intention-to-treat population occurred in 439 (62%) of 705 in the tenecteplase group versus 405 (58%) of 696 in the alteplase group (RR 1·07, 95% CI 0·98-1·16). The lower limit of the RR's 95% CI was greater than the non-inferiority margin. Symptomatic intracranial haemorrhage within 36 h was observed in 15 (2%) of 711 in the tenecteplase group and 13 (2%) of 706 in the alteplase group (RR 1·18, 95% CI 0·56-2·50). Mortality within 90 days occurred in 46 (7%) individuals in the tenecteplase group versus 35 (5%) in the alteplase group (RR 1·31, 95% CI 0·86-2·01). INTERPRETATION: Tenecteplase was non-inferior to alteplase in people with ischaemic stroke who were eligible for standard intravenous thrombolytic but ineligible for or refused endovascular thrombectomy. FUNDING: National Science and Technology Major Project, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, National Natural Science Foundation of China, and China Shijiazhuang Pharmaceutical Company Recomgen Pharmaceutical (Guangzhou).

Higher Procedural Volumes Are Associated with Faster Treatment Times, Better Functional Outcomes, and Lower Mortality in Patients Undergoing Endovascular Treatment for Acute Ischemic Stroke.

OBJECTIVE: We aimed to characterize the association of hospital procedural volumes with outcomes among acute ischemic stroke (AIS) patients undergoing endovascular therapy (EVT). METHODS: This was a retrospective, observational cohort study using data prospectively collected from January 1, 2016 to December 31, 2019 in the Get with the Guidelines-Stroke registry. Participants were derived from a cohort of 60,727 AIS patients treated with EVT within 24 hours at 626 hospitals. The primary cohort excluded patients with pretreatment National Institutes of Health Stroke Scale (NIHSS) < 6, onset-to-treatment time > 6 hours, and interhospital transfers. There were 2 secondary cohorts: (1) the EVT metrics cohort excluded patients with missing data on time from door to arterial puncture and (2) the intravenous thrombolysis (IVT) metrics cohort only included patients receiving IVT ≤4.5 hours after onset. RESULTS: The primary cohort (mean ± standard deviation age = 70.7 ± 14.8 years; 51.2% female; median [interquartile range] baseline NIHSS = 18.0 [13-22]; IVT use, 70.2%) comprised 21,209 patients across 595 hospitals. The EVT metrics cohort and IVT metrics cohort comprised 47,262 and 16,889 patients across 408 and 601 hospitals, respectively. Higher procedural volumes were significantly associated with higher odds (expressed as adjusted odds ratio [95% confidence interval] for every 10-case increase in volume) of discharge to home (1.03 [1.02-1.04]), functional independence at discharge (1.02 [1.01-1.04]), and lower rates of in-hospital mortality (0.96 [0.95-0.98]). All secondary measures were also associated with procedural volumes. INTERPRETATION: Among AIS patients primarily presenting to EVT-capable hospitals (excluding those transferred from one facility to another and those suffering in-hospital strokes), EVT at hospitals with higher procedural volumes was associated with faster treatment times, better discharge outcomes, and lower rates of in-hospital mortality. ANN NEUROL 2023.

Effects of Remote Patient Monitoring Use on Care Outcomes Among Medicare Patients With Hypertension : An Observational Study.

BACKGROUND: Remote patient monitoring (RPM) is a promising tool for improving chronic disease management. Use of RPM for hypertension monitoring is growing rapidly, raising concerns about increased spending. However, the effects of RPM are still unclear. OBJECTIVE: To estimate RPM's effect on hypertension care and spending. DESIGN: Matched observational study emulating a longitudinal, cluster randomized trial. After matching, effect estimates were derived from a regression analysis comparing changes in outcomes from 2019 to 2021 for patients with hypertension at high-RPM practices versus those at matched control practices with little RPM use. SETTING: Traditional Medicare. PATIENTS: Patients with hypertension. INTERVENTION: Receipt of care at a high-RPM practice. MEASUREMENTS: Primary outcomes included hypertension medication use (medication fills, adherence, and unique medications received), outpatient visit use, testing and imaging use, hypertension-related acute care use, and total hypertension-related spending. RESULTS: 192 high-RPM practices (with 19 978 patients with hypertension) were matched to 942 low-RPM control practices (with 95 029 patients with hypertension). Compared with patients with hypertension at matched low-RPM practices, patients with hypertension at high-RPM practices had a 3.3% (95% CI, 1.9% to 4.8%) relative increase in hypertension medication fills, a 1.6% (CI, 0.7% to 2.5%) increase in days' supply, and a 1.3% (CI, 0.2% to 2.4%) increase in unique medications received. Patients at high-RPM practices also had fewer hypertension-related acute care encounters (-9.3% [CI, -20.6% to 2.1%]) and reduced testing use (-5.9% [CI, -11.9% to 0.0%]). However, these patients also saw increases in primary care physician outpatient visits (7.2% [CI, -0.1% to 14.6%]) and a $274 [CI, $165 to $384]) increase in total hypertension-related spending. LIMITATION: Lacked blood pressure data; residual confounding. CONCLUSION: Patients in high-RPM practices had improved hypertension care outcomes but increased spending. PRIMARY FUNDING SOURCE: National Institute of Neurological Disorders and Stroke.

An Overview of Telehealth in the Management of Cardiovascular Disease: A Scientific Statement From the American Heart Association.

Telehealth enables the remote delivery of health care through telecommunication technologies and has substantially affected the evolving medical landscape. The COVID-19 pandemic accelerated the utilization of telehealth as health care professionals were forced to limit face-to-face in-person visits. It has been shown that information delivery, diagnosis, disease monitoring, and follow-up care can be conducted remotely, resulting in considerable changes specific to cardiovascular disease management. Despite increasing telehealth utilization, several factors such as technological infrastructure, reimbursement, and limited patient digital literacy can hinder the adoption of remote care. This scientific statement reviews definitions pertinent to telehealth discussions, summarizes the effect of telehealth utilization on cardiovascular and peripheral vascular disease care, and identifies obstacles to the adoption of telehealth that need to be addressed to improve health care accessibility and equity.

Association Between Endovascular Therapy Time to Treatment and Outcomes in Patients With Basilar Artery Occlusion.

BACKGROUND: Basilar artery occlusion (BAO) is a devastating condition without definitive evidence to guide treatment. Whereas the association between faster treatment times with endovascular therapy (EVT) and better outcomes in anterior circulation is well established, whether this relationship exists for patients with BAO is not well delineated. METHODS: We used individual-level patient data from the Get With The Guidelines-Stroke nationwide US registry prospectively collected from January 2015 to December 2019. We identified individuals with BAO treated with EVT within 24 hours of symptom onset. The primary outcomes examined were in-hospital mortality, discharge home, ambulatory at discharge, independent at discharge (modified Rankin Scale score 0 to 2), substantial reperfusion (modified Thrombolysis in Cerebral Infarction score 2b or 3), and symptomatic intracranial hemorrhage. Using logistic regression models, we evaluated the association between time from symptom onset to treatment with EVT and outcomes. RESULTS: Among 3015 patients with BAO treated with EVT, the mean age was 65.9 years, 38.8% were women, and the median National Institutes of Health Stroke Scale score at presentation was 17 (interquartile range, 8-26). Median onset to EVT time was 406 minutes (interquartile range, 252-688). From 2015 to 2019, there was an overall increase in the median onset to EVT times (380-411 minutes; P=0.016) but no significant change in the proportion of patients treated within 6 hours of symptom onset (48.4%-44.0%; P=0.17). After risk adjustment for patient and hospital-level factors, there were significantly lower odds of in-hospital mortality (adjusted odds ratio [aOR], 0.55 [95% CI, 0.45-0.68]) and symptomatic intracranial hemorrhage (aOR, 0.52 [95% CI, 0.32-0.84]) and significantly higher odds of ambulation at discharge (aOR, 1.72 [95% CI, 1.37-2.16]), discharge home (aOR, 2.19 [95% CI, 1.73-2.77]), and independence at discharge (aOR, 2.21 [95% CI, 1.66-2.95]) when onset to EVT time was ≤6 hours compared with >6 hours. The fastest decay in good outcomes per hour occurred within 6 hours of symptom onset. CONCLUSIONS: Among patients receiving EVT for BAO, faster treatment from symptom onset was associated with improved outcomes. These findings support efforts to achieve rapid treatment with EVT for patients with BAO.

Comparative Effectiveness and Safety of Seizure Prophylaxis Among Adults After Acute Ischemic Stroke.

BACKGROUND: Older adults occasionally receive seizure prophylaxis in an acute ischemic stroke (AIS) setting, despite safety concerns. There are no trial data available about the net impact of early seizure prophylaxis on post-AIS survival. METHODS: Using a stroke registry (American Heart Association's Get With The Guidelines) individually linked to electronic health records, we examined the effect of initiating seizure prophylaxis (ie, epilepsy-specific antiseizure drugs) within 7 days of an AIS admission versus not initiating in patients ≥65 years admitted for a new, nonsevere AIS (National Institutes of Health Stroke Severity score ≤20) between 2014 and 2021 with no recorded use of epilepsy-specific antiseizure drugs in the previous 3 months. We addressed confounding by using inverse-probability weights. We performed standardization accounting for pertinent clinical and health care factors (eg, National Institutes of Health Stroke Severity scale, prescription counts, seizure-like events). RESULTS: The study sample included 151 patients who received antiseizure drugs and 3020 who did not. The crude 30-day mortality risks were 219 deaths per 1000 patients among epilepsy-specific antiseizure drugs initiators and 120 deaths per 1000 among noninitiators. After standardization, the estimated mortality was 251 (95% CI, 190-307) deaths per 1000 among initiators and 120 (95% CI, 86-144) deaths per 1000 among noninitiators, corresponding to a risk difference of 131 (95% CI, 65-200) excess deaths per 1000 patients. In the prespecified subgroup analyses, the risk difference was 52 (95% CI, 11-72) among patients with minor AIS and 138 (95% CI, 52-222) among moderate-to-severe AIS patients. Similarly, the risk differences were 86 (95% CI, 18-118) and 157 (95% CI, 57-219) among patients aged 65 to 74 years and ≥75 years, respectively. CONCLUSIONS: There was a higher risk of 30-day mortality associated with initiating versus not initiating seizure prophylaxis within 7 days post-AIS. This study does not support the role of seizure prophylaxis in reducing 30-day poststroke mortality.

Antithrombotic and Statin Prescription After Intracerebral Hemorrhage in the Get With The Guidelines-Stroke Registry.

BACKGROUND: Survivors of intracerebral hemorrhage (ICH) face an increased risk of ischemic cardiovascular events. Current ICH guidelines do not provide definitive recommendations regarding the use of antithrombotic and statin therapies. We, therefore, sought to study practice patterns and factors associated with the use of such medications after ICH. METHODS: This was a cross-sectional study of patients with ICH in the Get With The Guidelines-Stroke registry, between 2011 and 2021. Patients transferred to another hospital, those who died during hospitalization, and those with missing information on discharge medications were excluded. The study exposure was the proportion of patients who were prescribed antithrombotic or statin medications. We first ascertained the proportion of patients prescribed antithrombotic and lipid-lowering medications at discharge overall and across strata defined by pre-ICH use and history of previous ischemic vascular disease or atrial fibrillation. We then studied factors associated with the discharge prescription of these medications after ICH, using multiple logistic regressions. RESULTS: In the final cohort, 50 416 (10.4%) of 486 586 patients with ICH were prescribed antiplatelet medications, 173 322 (35.1%) of 493 491 patients with ICH were prescribed statins, and 27 085 (5.4%) of 486 585 patients with ICH were prescribed anticoagulation therapy at discharge. The proportion of patients with antiplatelet therapy was 16.6% with pre-ICH use and 15.6% in those with previous ischemic vascular disease. Statins were prescribed to 41.1% and 43.7% of patients on previous lipid-lowering therapy and ischemic vascular disease, respectively. Anticoagulation therapy was restarted in 11.1% of patients. In logistic regression analysis, factors associated with higher use of antithrombotic or statin therapies after ICH were younger age, male sex, pre-ICH medication use, previous ischemic vascular disease, atrial fibrillation, lower admission National Institutes of Health Stroke Scale, longer length of stay, and favorable discharge outcome. CONCLUSIONS: Few patients with ICH are prescribed antithrombotic or statin therapies at hospital discharge. Given the emerging association between ICH and future major cardiovascular events, trials examining the net benefit of antiplatelet and lipid-lowering therapy after ICH are warranted.

Recent Vitamin K Antagonist Use and Intracranial Hemorrhage After Endovascular Thrombectomy for Acute Ischemic Stroke.

Importance: Use of oral vitamin K antagonists (VKAs) may place patients undergoing endovascular thrombectomy (EVT) for acute ischemic stroke caused by large vessel occlusion at increased risk of complications. Objective: To determine the association between recent use of a VKA and outcomes among patients selected to undergo EVT in clinical practice. Design, Setting, and Participants: Retrospective, observational cohort study based on the American Heart Association's Get With the Guidelines-Stroke Program between October 2015 and March 2020. From 594 participating hospitals in the US, 32 715 patients with acute ischemic stroke selected to undergo EVT within 6 hours of time last known to be well were included. Exposure: VKA use within the 7 days prior to hospital arrival. Main Outcome and Measures: The primary end point was symptomatic intracranial hemorrhage (sICH). Secondary end points included life-threatening systemic hemorrhage, another serious complication, any complications of reperfusion therapy, in-hospital mortality, and in-hospital mortality or discharge to hospice. Results: Of 32 715 patients (median age, 72 years; 50.7% female), 3087 (9.4%) had used a VKA (median international normalized ratio [INR], 1.5 [IQR, 1.2-1.9]) and 29 628 had not used a VKA prior to hospital presentation. Overall, prior VKA use was not significantly associated with an increased risk of sICH (211/3087 patients [6.8%] taking a VKA compared with 1904/29 628 patients [6.4%] not taking a VKA; adjusted odds ratio [OR], 1.12 [95% CI, 0.94-1.35]; adjusted risk difference, 0.69% [95% CI, -0.39% to 1.77%]). Among 830 patients taking a VKA with an INR greater than 1.7, sICH risk was significantly higher than in those not taking a VKA (8.3% vs 6.4%; adjusted OR, 1.88 [95% CI, 1.33-2.65]; adjusted risk difference, 4.03% [95% CI, 1.53%-6.53%]), while those with an INR of 1.7 or lower (n = 1585) had no significant difference in the risk of sICH (6.7% vs 6.4%; adjusted OR, 1.24 [95% CI, 0.87-1.76]; adjusted risk difference, 1.13% [95% CI, -0.79% to 3.04%]). Of 5 prespecified secondary end points, none showed a significant difference across VKA-exposed vs VKA-unexposed groups. Conclusions and Relevance: Among patients with acute ischemic stroke selected to receive EVT, VKA use within the preceding 7 days was not associated with a significantly increased risk of sICH overall. However, recent VKA use with a presenting INR greater than 1.7 was associated with a significantly increased risk of sICH compared with no use of anticoagulants.

Variation in patterns of telestroke usage during the COVID-19 pandemic.

OBJECTIVES: Early in the pandemic, there was a substantial increase in telestroke uptake among hospitals. The motivations for using telestroke during the pandemic might have been different than for hospitals that adopted telestroke previously. We compared stroke care at hospitals that adopted telestroke prior to the pandemic to care at hospitals that adopted telestroke during the pandemic. MATERIALS AND METHODS: Stroke episodes and telestroke use were identified in Medicare Fee-for-Service Data. Hospital and episode characteristics were compared between pre-pandemic (Jan. 2019-Mar. 2020) and pandemic (Apr. 2020-Dec. 2020) adopters. RESULTS: Hospital bed counts, critical access statuses, stroke volumes, clinical operating margins, shares of stroke care via telestroke, and vascular neurology consult rates did not differ significantly between pre-pandemic and pandemic-adopting hospitals. Hospitals that never adopted telestroke during the study period were more likely to be small critical access hospitals with low clinical operating margins. CONCLUSIONS: Compared to hospitals that adopted telestroke before the pandemic, hospitals that adopted telestroke during the pandemic were similar in characteristics and how they used telestroke.

Achieving More Rapid Door-to-Needle Times and Improved Outcomes in Acute Ischemic Stroke in a Nationwide Quality Improvement Intervention.

BACKGROUND: The benefits of tPA (tissue-type plasminogen activator) in acute ischemic stroke are time-dependent. However, delivery of thrombolytic therapy rapidly after hospital arrival was initially occurring infrequently in hospitals in the United States, discrepant with national guidelines. METHODS: We evaluated door-to-needle (DTN) times and clinical outcomes among patients with acute ischemic stroke receiving tPA before and after initiation of 2 successive nationwide quality improvement initiatives: Target: Stroke Phase I (2010-2013) and Target: Stroke Phase II (2014-2018) from 913 Get With The Guidelines-Stroke hospitals in the United States between April 2003 and September 2018. RESULTS: Among 154 221 patients receiving tPA within 3 hours of stroke symptom onset (median age 72 years, 50.1% female), median DTN times decreased from 78 minutes (interquartile range, 60-98) preintervention, to 66 minutes (51-87) during Phase I, and 50 minutes (37-66) during Phase II (P<0.001). Proportions of patients with DTN ≤60 minutes increased from 26.4% to 42.7% to 68.6% (P<0.001). Proportions of patients with DTN ≤45 minutes increased from 10.1% to 17.7% to 41.4% (P<0.001). By the end of the second intervention, 75.4% and 51.7% patients achieved 60-minute and 45-minute DTN goals. Compared with the preintervention period, hospitals during the second intervention period (2014-2018) achieved higher rates of tPA use (11.7% versus 5.6%; adjusted odds ratio, 2.43 [95% CI, 2.31-2.56]), lower in-hospital mortality (6.0% versus 10.0%; adjusted odds ratio, 0.69 [0.64-0.73]), fewer bleeding complication (3.4% versus 5.5%; adjusted odds ratio, 0.68 [0.62-0.74]), and higher rates of discharge to home (49.6% versus 35.7%; adjusted odds ratio, 1.43 [1.38-1.50]). Similar findings were found in sensitivity analyses of 185 501 patients receiving tPA within 4.5 hours of symptom onset. CONCLUSIONS: A nationwide quality improvement program for acute ischemic stroke was associated with substantial improvement in the timeliness of thrombolytic therapy start, increased thrombolytic treatment, and improved clinical outcomes.

Systematic Review of Sex Differences in Ischemic Strokes Among Young Adults: Are Young Women Disproportionately at Risk?

BACKGROUND AND PURPOSE: Recent evidence suggests that young women (18-45 years) may be at higher risk of ischemic strokes than men of the same age. The goal of this systematic review is to reconcile and synthesize existing evidence of sex differences among young adults with ischemic strokes. METHODS: We searched PubMed from January 2008 to July 2021 for relevant articles and reviews and consulted their references. We included original studies that (1) were population based and (2) reported stroke incidence by sex or sex-specific incidence rate ratios of young adults ≤45 years. We excluded studies that (1) omitted measurements of error for incidence rates or incidence rate ratios, (2) omitted age adjustment, and (3) were not in English. Statistical synthesis was performed to estimate sex difference by age group (≤35, 35-45, and ≤45) and stroke type. RESULTS: We found 19 studies that reported on sex-specific stroke incidence among young adults, including 3 that reported on overlapping data. Nine studies did not find a statistically significant sex difference among young adults ≤45 years. Three studies found higher rates of ischemic stroke among men among young adults ≥30 to 35 years. Four studies found more women with ischemic strokes among young adults ≤35 years. Overall, in young adults ≤35 years, the estimated effect size favored more ischemic strokes in women (incidence rate ratio, 1.44 [1.18-1.76], I2=82%) and a nonsignificant sex difference in young adults 35 to 45 years (incidence rate ratio, 1.08 [0.85-1.38], I2=95%). CONCLUSIONS: Overall, there were 44% more women ≤35 years with ischemic strokes than men. This gap narrows in young adults, 35 to 45 years, and there is conflicting evidence whether more men or women have ischemic strokes in the 35 to 45 age group.

Frequency and Prognostic Significance of Clinical Fluctuations Before Hospital Arrival in Stroke.

BACKGROUND AND PURPOSE: Clinical fluctuations in ischemic stroke symptoms are common, but fluctuations before hospital arrival have not been previously characterized. METHODS: A standardized qualitative assessment of fluctuations before hospital arrival was obtained in an observational study that enrolled patients with mild ischemic stroke symptoms (National Institutes of Health Stroke Scale [NIHSS] score of 0-5) present on arrival to hospital within 4.5 hours of onset, in a subset of 100 hospitals participating in the Get With The Guidelines-Stroke quality improvement program. The number of fluctuations, direction, and the overall improvement or worsening was recorded based on reports from the patient, family, or paramedics. Baseline NIHSS on arrival and at 72 hours (or discharge if before) and final diagnosis and stroke subtype were collected. Outcomes at 90 days included the modified Rankin Scale, Barthel Index, Stroke Impact Scale 16, and European Quality of Life. Prehospital fluctuations were examined in relation to hospital NIHSS change (admission to 72 hours or discharge) and 90-day outcomes. RESULTS: Among 1588 participants, prehospital fluctuations, consisting of improvement, worsening, or both were observed in 35.5%: 25.1% improved once, 5.3% worsened once, and 5.1% had more than 1 fluctuation. Those who improved were less likely and those who worsened were more likely to receive alteplase. Those who improved before hospital arrival had lower change in the hospital NIHSS than those who did not fluctuate. Better adjusted 90-day outcomes were noted in those with prehospital improvement compared to those without any fluctuations. CONCLUSIONS: Fluctuations in neurological symptoms and signs are common in the prehospital setting. Prehospital improvement was associated with better 90-day outcomes, controlling for admission NIHSS and alteplase treatment. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02072681.

Alteplase for Stroke With Unknown Onset Time in Chronic Kidney Disease: A Pooled Analysis of Individual Participant Data.

BACKGROUND: Although chronic kidney disease (CKD) is associated with worse stroke outcomes, data regarding the influence of CKD on intravenous thrombolysis outcomes are scarce. We sought to assess the efficacy and safety of intravenous thrombolysis for acute ischemic stroke with unknown onset time in patients with CKD. METHODS: Patients with an acute stroke of unknown onset time from the EOS trials (Evaluation of Unknown Onset Stroke Thrombolysis) collaboration were evaluated using an individual patient-level database of randomized controlled trials comparing intravenous thrombolysis with placebo/standard treatment. CKD was defined as baseline estimated glomerular filtration rate of <60 ml/min/1.73m2 Mixed-effect logistic-regression analysis was performed to evaluate treatment effects. A favorable outcome was defined as a modified Rankin Scale score of 0 to 1 at 90 days. Safety outcomes were symptomatic intracranial hemorrhage at 22 to 36 hours and 90-day mortality. RESULTS: Baseline data on renal function were available for 688 of 843 patients. Of these, CKD was present in 146 (21%), including 69 of 351 patients receiving alteplase and 77 of 337 patients receiving placebo/standard treatment. Overall, treatment with alteplase was associated with higher odds of favorable outcome, and CKD did not modify the treatment effect (Pinteraction=0.834). A favorable outcome was observed in 31 of 69 (46%) patients with CKD in the alteplase group and in 28 of 77 (36%) patients with CKD in the control group (adjusted odds ratio, 1.19 [95% CI, 0.55-2.58]). Among patients with CKD, symptomatic intracranial hemorrhage occurred in 2 patients (3%) in the alteplase group but in none of the controls (P=0.133). At 90 days, death was reported in 3 patients (4%) in the alteplase group compared with 2 patients (3%) in the controls (P=0.539). CONCLUSIONS: The present analysis indicates that the benefit of alteplase does not differ between stroke patients with unknown onset time with and without CKD, although the statistical power was lacking to confirm the efficacy in subgroups. This study only applies to mild-to-moderate or predialysis CKD.

Acute Ischemic Stroke, Depressed Left Ventricular Ejection Fraction, and Sinus Rhythm: Prevalence and Practice Patterns.

BACKGROUND: There are limited data about the epidemiology and secondary stroke prevention strategies used for patients with depressed left ventricular ejection fraction (LVEF) and sinus rhythm following an acute ischemic stroke (AIS). We sought to describe the prevalence of LVEF ≤40% and sinus rhythm among patients with AIS and antithrombotic treatment practice in a multi-center cohort from 2002 to 2018. METHODS: This was a multi-center, retrospective cohort study comprised of patients with AIS hospitalized in the Greater Cincinnati Northern Kentucky Stroke Study and 4 academic, hospital-based cohorts in the United States. A 1-stage meta-analysis of proportions was undertaken to calculate a pooled prevalence. Univariate analyses and an adjusted multivariable logistic regression model were performed to identify demographic, clinical, and echocardiographic characteristics associated with being prescribed an anticoagulant upon AIS hospitalization discharge. RESULTS: Among 14 338 patients with AIS with documented LVEF during the stroke hospitalization, the weighted pooled prevalence of LVEF ≤40% and sinus rhythm was 5.0% (95% CI, 4.1-6.0%; I2, 84.4%). Of 524 patients with no cardiac thrombus and no prior indication for anticoagulant who survived postdischarge, 200 (38%) were discharged on anticoagulant, 289 (55%) were discharged on antiplatelet therapy only, and 35 (7%) on neither. There was heterogeneity by site in the proportion discharged with an anticoagulant (22% to 45%, P<0.0001). Cohort site and National Institutes of Health Stroke Severity scale >8 (odds ratio, 2.0 [95% CI, 1.1-3.8]) were significant, independent predictors of being discharged with an anticoagulant in an adjusted analysis. CONCLUSIONS: Nearly 5% of patients with AIS have a depressed LVEF and are in sinus rhythm. There is significant variation in the clinical practice of antithrombotic therapy prescription by site and stroke severity. Given this clinical equipoise, further study is needed to define optimal antithrombotic treatment regimens for secondary stroke prevention in this patient population.