Demaerschalk, Bart M.

Background: Atrial fibrillation (AF) is an important modifiable and independent risk factor for stroke. AF is associated with 2-4% annual risk for first time stroke and about 8% annually for recurrent stroke. Anticoagulant therapy reduces the risk by 60%, while the relative risk reduction (RRR) obtained from antiplatelet therapy is only 20%. The effect is more robust for secondary than for primary prevention. Risk stratification schemes are utilized to assess an individual’s risk of future stroke and to determine the optimal antithrombotic or anticoagulation regimen for stroke prevention. Despite Warfarin’s superiority over antiplatelet therapy to reduce the risk of AF related systemic embolism, Warfarin is largely underutilized. The aim of this study was to determine the frequency and reasons behind withholding anticoagulation in patient with AF related cardioembolic stroke in our institution. Method: We extracted patients from our Get With The Guideline’s (GWTG) database who were admitted to Mayo Clinic AZ between January 2004 and December 2009. Two authors (TK and NL) independently identified all patients with the diagnosis of atrial fibrillation who were not prescribed Warfarin therapy upon discharge, then reviewed to identify the reason(s) why anticoagulation was not initiated. Factors such as discharge disposition (home, acute rehabilitation, long term nursing facility, hospice, other) and functional status (able to ambulate independently, with assistance, unable to ambulate, or not documented) were also assessed to help support the decision process. Results: From a total of 1295 patients, 305 with AF were identified. Patients who expired 48 (3.7%) from un-related causes were excluded. Of the 257 patients, 206 (80.2%) were anticoagulated and 51 (19.8%) were not anticoagulated. We found that in the anticoagulated group, patients discharged home were more likely to receive anticoagulation (89.2%), followed by those discharged to acute rehabilitation and skilled nursing facilities (77%). Those discharged to hospice were the least likely to receive anticoagulation (6.4%). In addition, patients with greater functional ability were also more likely to receive anticoagulation (independent 89.8%, vs. assisted 76.7%, vs. non-ambulatory 33.3%; p<0.0001). Reasons to withhold anticoagulation therapy at discharge included terminal illness/comfort measures only (40.0%); risk/discomfort due to bleeding (24%); risk of falls (13.0%); and patient refusal (9.0%). Discussion: Based on the results, we conclude that functional status and disposition at discharge are significant factors influencing the decision to anticoagulate after cardioembolic stroke attributed to AF.

Background: The implementation of telemedicine for stroke has played a vital role in creating universal access to emergency stroke care for patients in both rural and urban communities, regardless of location or hospital resources. Objective: We evaluated the hypothesis that there is no difference in speed of assessment between vascular neurologist (VN) robotic telepresence and standard VN supervised stroke alert patients in a primary stroke center. Methods: A retrospective stroke alert database review was used to identify all robotic telepresence and standardly supervised stroke alert patient assessments at Mayo Clinic Hospital Emergency Department from 2009 to 2012. The robotic telepresence cohort was compared to a random sample of standard stroke alert patients, with an equal number of patients selected from each year. The primary outcome measure was the duration of assessment from stroke alert activation to treatment or downgrade. Results: The sample size was 196 subjects. The mean duration of time from stroke alert activation to initiation of IV thrombolytic treatment or downgrade was 8.6 minutes longer in the robotic telepresence group than in the standard group ( P =0.03). There was a higher percentage of patients diagnosed with acute stroke in the robotic stroke alert group than in the standard stroke alert group (77% vs 60%, P =0.01). Controlling for acute stroke, age, and NIHSS did not significantly reduce the time difference between groups. Among the subgroup of acute ischemic stroke patients requiring IV thrombolysis, the mean duration of time from activation to treatment was 18 minutes longer in the robotic group than in the standard group ( P =0.01). Safety outcomes including thrombolysis protocol violations (0% vs 1%), post-thrombolysis symptomatic intracranial hemorrhagic complications (3% vs 1%), and death during hospitalization (8% vs 6%) were low in the robotic group and not significantly different from that in the standard group. Conclusion: Standard VN supervised acute stroke team assessments are swifter than those supervised by robotic telepresence. Safety outcomes of robotic telepresence supervised stroke alerts are excellent, and this modality may be preferred in circumstances when a VN is not immediately available on-site.

Purpose: The safety of revascularization for asymptomatic carotid stenosis, and the efficacy of medical therapy for stroke prevention have improved. Therefore, results of prior randomized trials may not apply to current treatment decisions. The NINDS-funded CREST-2 will compare carotid endarterectomy and intensive medical therapy (IMT) versus IMT alone (n=1240), and carotid stenting and IMT versus IMT alone (n=1240) in asymptomatic patients with≥70% stenosis. Materials & Methods: CREST-2 consists of two parallel randomized clinical trials to be conducted at a target of ≈120 centers, including within NINDS StrokeNet. The composite primary outcome is stroke or death during the peri-procedural period or ipsilateral ischemic stroke thereafter up to 4 years. Blinded assessment of cognition will be done periodically. Centrally directed IMT includes tight control of blood pressure (systolic target <140 mm Hg) and cholesterol (LDL target <70 mg/dl) as well as lifestyle coaching. Results: As of June 12, 2015, 94 centers have been approved by the Site Selection Committee. Credentialing is ongoing, with 198 approved surgeons and 64 approved interventionists; 124 additional conditionally approved interventionists will be able to submit additional cases for review under the CREST-2 Registry. The Centers for Medicare and Medicaid will offer CAS reimbursement for Registry enrollees. As of June 12, 2015, there are 39 actively enrolling centers, and 37 patients have been randomized. Conclusion: CREST-2 is designed to identify the best approach for asymptomatic carotid stenosis. The first patient was randomized in December, 2014. An update will be provided regarding the numbers of patients randomized, centers certified, as well as surgeons and interventionists fully approved. Registration: ClinicalTrials.gov Identifier: NCT02089217

Background: Presence of atherosclerotic disease in more than one vascular bed (polyvascular disease) is associated with an increased risk of long-term vascular events. In the setting of asymptomatic carotid stenosis, the predictors of disease in other vascular beds is not well delineated. Objective: To identify the frequency and predictors of disease in other vascular beds the CREST 2 randomized trial population with hemodynamically significant stenosis. Methods: Recorded baseline characteristics among CREST 2 participants included: demographics, past medical history, lifestyle factors, and laboratory studies. Each variable was tested against three potential definitions of disease in other beds (cardiac, peripheral arterial disease (PAD) or disease in cardiac + PAD). Statistical analysis was done with Chi square and t tests as appropriate. Results: Data from 1447 patients were available for analysis. In these subjects with carotid disease, 51% also had cardiac disease, 24% also had PAD, and 16% had disease in in both cardiac and PAD. There was no relationship between age or race and presence of disease in other beds. Those with cardiac disease were more likely to be male. Diabetes, hypertension, hypercholesterolemia, and former history of smoking were all more common in those with either cardiac and PAD (TABLE). Elevated triglyceride and low HDL levels were also associated with all three definitions of disease in other beds. Those with either PAD or cardiac + PAD were more likely to be current smokers. Conclusions: Among CREST 2 participants, several medical conditions and lifestyle factors were associated with an increased frequency of disease in other vascular beds. Smoking, in particular, appears to be more common in those with PAD. Future analyses will address whether those with disease in other beds have higher rates of stroke or death.

Baseline Differences in Risk Factor Control and Medication Use Between 2 Trials Employing Intensive Medical Management (SAMMPRIS & CREST2) Background: The CREST2 trial Intensive Medical Management (IMM) protocol was adapted from the SAMMPRIS trial. However, since the 2011 publication of initial results of SAMMPRIS, there has been a greater appreciation for the importance of risk factor control in patients at risk of stroke associated with atherosclerosis. Therefore, we sought to determine differences in baseline risk factor control and medication use between SAMMPRIS and CREST2. Methods: Baseline risk factor and medication use data from 451 patients enrolled in SAMMPRIS (2008-2011) with severe symptomatic intracranial atherosclerosis and 1473 patients enrolled in CREST2 (2014-2019) with severe asymptomatic carotid stenosis were compared using the Chi-square test and t-test. Results: The Table shows baseline risk factor values and medications. SAMMPRIS patients were younger but had significantly worse risk factor control than CREST2 patients for all measures. There was no significant difference in statin use at baseline, but the mean SAMMPRIS subjects’ LDL was 16.1 mg/dL higher than in CREST2. CREST2 patients had higher rates of use of angiotensin receptor blockers (ARB), calcium channel blockers (CCB), and thiazides, but lower rates of use of angiotensin converting enzyme (ACE) inhibitors. Conclusions: Despite being older, CREST2 patients have significantly better baseline risk factor profiles than SAMMPRIS patients. This could be due to greater appreciation of the importance of risk factor control and healthy lifestyle habits for stroke prevention or more aggressive treatment targets in guideline recommendations. Although risk factor control appears to be improving since SAMMPRIS, many CREST2 patients are still not meeting recommended risk factor goals at baseline and may benefit from IMM protocols.

Introduction: There is a lack of data regarding financial trends for procedural reimbursement in stroke care. An understanding of such trends is important as progress is made to advance agreeable reimbursement models in the care of stroke patients. The purpose of this study was to evaluate monetary trends in Medicare reimbursement rates for commonly utilized procedures in stroke care from 2000 to 2019. Methods: Reimbursement data for Current Procedural Terminology (CPT) codes was extracted from the Centers for Medicare & Medicaid Services. CPT codes were determined by frequency of procedures for Stroke-related ICD codes at our institution. All monetary data was adjusted for inflation to 2019 US dollars utilizing changes to the United States consumer price index. Results: After adjusting for inflation, the average reimbursement for all four included procedures within hemorrhagic stroke (ICD I60-I62) decreased by 18.4% from 2000 to 2019. The average reimbursement for two procedures within ischemic stroke (ICD I63), craniotomy and thrombectomy, increased by 3.5% (2003 -2019) and increased 3.0% (2016-2019), respectively. Data was not available for craniotomy prior to 2003, and not available for thrombectomy prior to 2016. Further, the adjusted reimbursement rate for included telestroke codes decreased by 12.1% from 2010-2019. All other included procedures decreased by 3.5% throughout this time. The difference in reimbursement rate between telestroke and other stroke-related procedures was statistically significant (p < .0001). Conclusion: To our knowledge, this is the first study to evaluate trends in Medicare reimbursement for stroke care. When adjusted for inflation, Medicare reimbursement for included procedures has steadily decreased from 2000 to 2019. Increased awareness of these trends is important to assure continued access to quality stroke care in the United States.

Introduction: Careful selection and timely activation of clinical sites in multicenter clinical trials is critical for successful enrollment, subject safety, and generalizability of results. Methods: In the Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial (CREST-2), a multidisciplinary Site Selection Committee evaluated applicants referred via participation in CREST, CREST principal investigators (PIs) and other investigators, StrokeNet and industry partners. Data for consideration included performance metrics in CREST and other carotid trials and a site selection questionnaire containing information on the investigators as well as quantitative data on carotid procedures performed. Any FDA warning letters were reviewed. Results: The Committee met bi-weekly for 36 months (n=64 meetings). Applications from 176 sites between March 2014 and July 2016 were evaluated: 153 were approved, 7 are under Committee review, 5 were approved but withdrew, 5 were placed on a waiting list, and 6 were rejected. One-hundred-four sites have completed the regulatory and training requirements to randomize: 51 (49%) academic medical centers, 31 (30%) private hospital-based centers, 16 (15%) private office-based practices, and 6 (6%) Veterans Administration medical centers. The mean times from application-to- approval was 5.2 weeks (interquartile range, 1.9, 6.2), and from approval-to-randomization status was 46.7 weeks (interquartile range, 35.4, 51.7). Specialties of the 104 site PIs are vascular surgery for 35 (33.7%), cardiology for 30 (28.8%), neurology for 25 (24%), neurosurgery for 8 (7.7%), interventional radiology for 4 (3.8%), and interventional neuroradiology for 2 (1.9%). Conclusions: Careful site selection is time-consuming for prospective sites and for trial leadership. Times from application-to-site-approval were modest (mean = 5.2 weeks), in contrast to the times for completing regulatory and training requirements (mean = 46.7 weeks). However, subject enrollment by teams from a wide range of medical centers led by a multi-disciplinary cohort of PIs will promote the generalizability of trial results.

Background: Stroke is a leading cause of disability worldwide. Selective serotonin reuptake inhibitors are often prescribed following stroke due to high rates of depression. Interest in selective serotonin reuptake inhibitor use for poststroke motor and functional recovery was generated after the publication of the Fluoxetine for motor recovery after acute ischemic stroke (FLAME) trial in 2011, which showed improved motor recovery in ischemic stroke patients with moderate to severe motor deficits. The objective of this study was to critically assess current evidence regarding the use of fluoxetine compared with placebo for poststroke functional recovery. Methods: The objective was addressed through the development of a structured critically appraised topic. This included a clinical scenario and question, literature search, critical appraisal, results, evidence summary, commentary, and clinical bottom line conclusions. Participants included consultant and resident neurologists, medical librarian, clinical epidemiologists, and content experts in the field of cerebrovascular neurology and physical medicine and rehabilitation. Results: A randomized, placebo-controlled clinical trial was selected for critical appraisal. This trial compared the functional outcomes of subjects poststroke receiving fluoxetine versus placebo. There was no significant difference in functional outcome measured by the Modified Rankin Scale between the 2 groups. Prespecified secondary analysis showed significantly decreased rates of depression in the fluoxetine group, but significantly increased rates of bone fracture. Conclusion: Among patients with stroke, early initiation of fluoxetine did not result in improved functional recovery. Lower rates of depression were observed in the fluoxetine-treated group; however these patients experienced higher rates of bone fracture.

Background and purpose: In-hospital stroke-onset assessment and management present numerous challenges, especially in community hospitals. Comprehensive analysis of key stroke care metrics in community-based primary stroke centers is under-studied. Methods: Medical records were reviewed for patients admitted to a community hospital for non-cerebrovascular indications and for whom a stroke alert was activated between 2013 and 2019. Demographic, clinical, radiologic and laboratory information were collected for each incident stroke. Descriptive statistical analysis was employed. When applicable, Kruskal-Wallis and Chi-Square tests were used to compare median values and categorical data between pre-specified groups. Statistical significance was set at alpha = 0.05. Results: There were 192 patients with in-hospital stroke-alert activation; mean age (SD) was 71.0 years (15.0), 49.5% female. 51.6% (99/192) had in-hospital ischemic and hemorrhagic stroke. The most frequent mechanism of stroke was cardioembolism. Upon stroke activation, 45.8% had ischemic stroke while 40.1% had stroke mimics. Stroke team response time from activation was 26 minutes for all in-hospital activations. Intravenous thrombolysis was utilized in 8% of those with ischemic stroke; 3.4% were transferred for consideration of endovascular thrombectomy. In-hospital mortality was 17.7%, and the proportion of patients discharged to home was 34.4% for all activations. Conclusion: The in-hospital stroke mortality was high, and the proportions of patients who either received or were considered for acute intervention were low. Quality improvement targeting increased use of acute stroke intervention in eligible patients and reducing hospital mortality in this patient cohort is needed.