In mild ischemic stroke or high-risk TIA, DAPT started ≤72 h after onset reduced new stroke and increased bleeding at 90 d.

SOURCE CITATION: Gao Y, Chen W, Pan Y, et al; INSPIRES Investigators. Dual antiplatelet treatment up to 72 hours after ischemic stroke. N Engl J Med. 2023;389:2413-2424. 38157499.

Heterogeneity of State Stroke Center Certification and Designation Processes.

BACKGROUND: Stroke centers are critical for the timely diagnosis and treatment of acute stroke and have been associated with improved treatment and outcomes; however, variability exists in the definitions and processes used to certify and designate these centers. Our study categorizes state stroke center certification and designation processes and provides examples of state processes across the United States, specifically in states with independent designation processes that do not rely on national certification. METHODS: In this cross-sectional study from September 2022 to April 2023, we used peer-reviewed literature, primary source documents from states, and communication with state officials in all 50 states to capture each state's process for stroke center certification and designation. We categorized this information and outlined examples of processes in each category. RESULTS: Our cross-sectional study of state-level stroke center certification and designation processes across states reveals significant heterogeneity in the terminology used to describe state processes and the processes themselves. We identify 3 main categories of state processes: No State Certification or Designation Process (category A; n=12), State Designation Reliant on National Certification Only (category B; n=24), and State Has Option for Self-Certification or Independent Designation (category C; n=14). Furthermore, we describe 3 subcategories of self-certification or independent state designation processes: State Relies on Self-Certification or Independent Designation for Acute Stroke Ready Hospital or Equivalent (category C1; n=3), State Has Hybrid Model for Acute Stroke Ready Hospital or Equivalent (category C2; n=5), and State Has Hybrid Model for Primary Stroke Center and Above (category C3; n=6). CONCLUSIONS: Our study found significant heterogeneity in state-level processes. A better understanding of how these differences may impact the rigor of each process and clinical performance of stroke centers is worthy of further investigation.

In ischemic stroke without large or medium vessel occlusion, tirofiban increased likelihood of an excellent outcome.

SOURCE CITATION: Zi W, Song J, Kong W, et al; RESCUE BT2 Investigators. Tirofiban for stroke without large or medium-sized vessel occlusion. N Engl J Med. 2023;388:2025-2036. 37256974.

After ICH, starting long-term therapeutic oral anticoagulation in patients with AF reduces MACE at 1 to 3 y.

SOURCE CITATION: Cochrane A, Chen C, Stephen J, et al. Antithrombotic treatment after stroke due to intracerebral haemorrhage. Cochrane Database Syst Rev. 2023;1:CD012144. 36700520.

Identifying Best Practices to Improve Evaluation and Management of In-Hospital Stroke: A Scientific Statement From the American Heart Association.

This scientific statement describes a path to optimizing care for patients who experience an in-hospital stroke. Although these patients are in a monitored environment, their evaluation and treatment are often delayed compared with patients presenting to the emergency department, contributing to higher rates of morbidity and mortality. Reducing delays and optimizing treatment for patients with in-hospital stroke could improve outcomes. This scientific statement calls for the development of hospital systems of care and targeted quality improvement for in-hospital stroke. We propose 5 core elements to optimize in-hospital stroke care: 1. Deliver stroke training to all hospital staff, including how to activate in-hospital stroke alerts. 2. Create rapid response teams with dedicated stroke training and immediate access to neurological expertise. 3. Standardize the evaluation of patients with potential in-hospital stroke with physical assessment and imaging. 4. Address barriers to treatment potentially, including interfacility transfer to advanced stroke treatment. 5. Establish an in-hospital stroke quality oversight program delivering data-driven performance feedback and driving targeted quality improvement efforts. Additional research is needed to better understand how to reduce the incidence, morbidity, and mortality of in-hospital stroke.

Ischemic Stroke in Patients With Pulmonary Arteriovenous Fistulas.

BACKGROUND AND PURPOSE: Pulmonary arteriovenous fistulas (PAVFs) are a treatable cause of acute ischemic stroke (AIS), not mentioned in current American Heart/Stroke Association guidelines. PAVFs are recognized as an important complication of hereditary hemorrhagic telangiectasia. METHODS: The prevalence of PAVF and hereditary hemorrhagic telangiectasia among patients admitted with AIS in the United States (2005-2014) was retrospectively studied, utilizing the Nationwide Inpatient Sample database. Clinical factors, morbidity, mortality, and management were compared in AIS patients with and without PAVF/hereditary hemorrhagic telangiectasia. RESULTS: Of 4 271 910 patients admitted with AIS, 822 (0.02%) were diagnosed with PAVF. Among them, 106 of 822 (12.9%) were diagnosed with hereditary hemorrhagic telangiectasia. The prevalence of PAVF per million AIS admissions rose from 197 in 2005 to 368 in 2014 (Ptrend, 0.026). Patients with PAVF were younger than AIS patients without PAVF (median age, 57.5 versus 72.5 years), had lower age-adjusted inpatient morbidity (defined as any discharge other than home; 39.6% versus 46.9%), and had lower in-hospital case fatality rates (1.8% versus 5.1%). Multivariate analyses identified the following as independent risk markers (odds ratio [95% CI]) for AIS in patients with PAVF: hypoxemia (8.4 [6.3-11.2]), pulmonary hemorrhage (7.9 [4.1-15.1]), pulmonary hypertension (4.3 [4.1-15.1]), patent foramen ovale (4.2 [3.5-5.1]), epistaxis (3.7 [2.1-6.8]), venous thrombosis (2.6 [1.9-3.6]), and iron deficiency anemia (2 [1.5-2.7]). Patients with and without PAVF received intravenous thrombolytics at a similar rate (5.9% versus 5.8%), but those with PAVF did not receive mechanical thrombectomy (0% versus 0.7%). CONCLUSIONS: Pulmonary arteriovenous fistula-related ischemic stroke represents an important younger demographic with a unique set of stroke risk markers, including treatable conditions such as causal PAVFs and iron deficiency anemia.

In ischemic stroke, thrombectomy alone was noninferior to thrombectomy plus alteplase for functional outcome at 90 days.

SOURCE CITATION: Yang P, Zhang Y, Zhang L, et al. Endovascular thrombectomy with or without intravenous alteplase in acute stroke. N Engl J Med. 2020;382:1981-93. 32374959.

Risk of Stroke Outcomes in Atrial Fibrillation Patients Treated with Rivaroxaban and Warfarin.

OBJECTIVES: In a previous real-world study, rivaroxaban reduced the risk of stroke overall and severe stroke compared with warfarin in patients with nonvalvular atrial fibrillation (NVAF). The aim of this study was to assess the reproducibility in a different database of our previously observed results (Alberts M, et al. Stroke. 2020;51:549-555) on the risk of severe stroke among NVAF patients in a different population treated with rivaroxaban or warfarin. MATERIAL AND METHODS: This retrospective cohort study included patients from the IBM® MarketScan® Commercial and Medicare databases (2011-2019) who initiated rivaroxaban or warfarin after a diagnosis of NVAF, had ≥6 months of continuous health plan enrollment, had a CHA2DS2-VASc score ≥2, and had no history of stroke or anticoagulant use. Patient data were assessed until the earliest occurrence of a primary inpatient diagnosis of stroke, death, end of health plan enrollment, or end of study. Stroke severity was defined by National Institutes of Health Stroke Scale (NIHSS) score, imputed by random forest model. Cox proportional hazard regression was used to compare risk of stroke between cohorts, balanced by inverse probability of treatment weighting. RESULTS: The mean observation period from index date to either stroke, or end of eligibility or end of data was 28 months. Data from 13,599 rivaroxaban and 39,861 warfarin patients were included. Stroke occurred in 272 rivaroxaban-treated patients (0.97/100 person-years [PY]) and 1,303 warfarin-treated patients (1.32/100 PY). Rivaroxaban patients had lower risk for stroke overall (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.76-0.88) and for minor (NIHSS 1 to <5; HR, 0.83; 95% CI, 0.74-0.93), moderate (NIHSS 5 to <16; HR, 0.88; 95% CI, 0.78-0.99), and severe stroke (NIHSS 16 to 42; HR, 0.44; 95% CI, 0.22-0.91). CONCLUSIONS: The results of this study in a larger population of NVAF patients align with previous real-world findings and the ROCKET-AF trial by showing improved stroke prevention with rivaroxaban versus warfarin across all stroke severities.

Novel GDF2 Gene Mutation Associated with Pulmonary Arteriovenous Malformation.

Pulmonary arteriovenous malformations (PAVMs) are pathologic low-resistance conduits between a pulmonary artery and vein. Over 80% PAVMs occur in patients with hereditary hemorrhagic telangiectasia (HHT) and result from mutations in the transforming growth factor-beta signaling pathway. Mutations in the Growth Differentiation Factor 2 (GDF2) gene have recently been described to result in a vascular-anomaly syndrome with phenotypic overlap with HHT. We report a 43-year-old woman with a PAVM related ischemic stroke who was subsequently found to have a novel GDF2 gene mutation. The patient underwent coil-embolization of the PAVM with stable clinical and radiographic follow-up. It is important to diagnose PAVMs as they are an important cause of stroke-in-young; and can be treated definitively, reducing risk of recurrent stroke and migraine.

Recommendations for the Establishment of Stroke Systems of Care: A 2019 Update.

In 2005, the American Stroke Association published recommendations for the establishment of stroke systems of care and in 2013 expanded on them with a statement on interactions within stroke systems of care. The aim of this policy statement is to provide a comprehensive review of the scientific evidence evaluating stroke systems of care to date and to update the American Stroke Association recommendations on the basis of improvements in stroke systems of care. Over the past decade, stroke systems of care have seen vast improvements in endovascular therapy, neurocritical care, and stroke center certification, in addition to the advent of innovations, such as telestroke and mobile stroke units, in the context of significant changes in the organization of healthcare policy in the United States. This statement provides an update to prior publications to help guide policymakers and public healthcare agencies in continually updating their stroke systems of care in light of these changes. This statement and its recommendations span primordial and primary prevention, acute stroke recognition and activation of emergency medical services, triage to appropriate facilities, designation of and treatment at stroke centers, secondary prevention at hospital discharge, and rehabilitation and recovery.

Safety and effectiveness of oral factor Xa inhibitors versus warfarin in nonvalvular atrial fibrillation patients at high-risk for falls.

Prescribers' concern regarding falls resulting in intracranial hemorrhage is often cited as a justification for under-utilization of oral anticoagulation. We evaluated the safety and effectiveness of oral factor Xa inhibitors versus warfarin in nonvalvular atrial fibrillation patients at high-risk for falls. Using MarketScan claims from 11/2012-3/2017, we identified adult, oral anticoagulation-naïve, new-initiators of oral factor Xa inhibitors or warfarin with nonvalvular atrial fibrillation, ≥ 12 months of insurance coverage prior to starting oral anticoagulation and a predicted 2-year risk of falls ≥ 15%. Differences in baseline covariates between cohorts were balanced using inverse probability-of-treatment weights based on propensity scores. Hazard ratios (HRs) and 95% confidence intervals (CIs) for intracranial hemorrhage and stroke or systemic embolism were estimated. Among 25,144 nonvalvular atrial fibrillation patients at high-risk for falls (observed fall rate = 11.8%/person-year), oral factor Xa inhibitor use was associated with a 43% (95% CI = 5-65%) reduced hazard of intracranial hemorrhage compared to warfarin. Oral factor Xa inhibitors did not significantly reduce the hazard of stroke or systemic embolism versus warfarin (HR = 0.86, 95% CI = 0.66-1.11). Findings for the intracranial hemorrhage and stroke or systemic embolism endpoints were similar when apixaban and rivaroxaban were evaluated separately versus warfarin (p-interaction ≥ 0.64 for all). Oral factor Xa inhibitors reduced patients' risk of intracranial hemorrhage and were at least as effective in preventing stroke or systemic embolism as warfarin in nonvalvular atrial fibrillation patients at high-risk for falls.

Evidence-Based Policy Making: Assessment of the American Heart Association's Strategic Policy Portfolio: A Policy Statement From the American Heart Association.

BACKGROUND: American Heart Association (AHA) public policy advocacy strategies are based on its Strategic Impact Goals. The writing group appraised the evidence behind AHA's policies to determine how well they address the association's 2020 cardiovascular health (CVH) metrics and cardiovascular disease (CVD) management indicators and identified research needed to fill gaps in policy and support further policy development. METHODS AND RESULTS: The AHA policy research department first identified current AHA policies specific to each CVH metric and CVD management indicator and the evidence underlying each policy. Writing group members then reviewed each policy and the related metrics and indicators. The results of each review were summarized, and topic-specific priorities and overarching themes for future policy research were proposed. There was generally close alignment between current AHA policies and the 2020 CVH metrics and CVD management indicators; however, certain specific policies still lack a robust evidence base. For CVH metrics, the distinction between policies for adults (age ≥20 years) and children (<20 years) was often not considered, although policy approaches may differ importantly by age. Inclusion of all those <20 years of age as a single group also ignores important differences in policy needs for infants, children, adolescents, and young adults. For CVD management indicators, specific quantitative targets analogous to criteria for ideal, intermediate, and poor CVH are lacking but needed to assess progress toward the 2020 goal to reduce deaths from CVDs and stroke. New research in support of current policies needs to focus on the evaluation of their translation and implementation through expanded application of implementation science. Focused basic, clinical, and population research is required to expand and strengthen the evidence base for the development of new policies. Evaluation of the impact of targeted improvements in population health through strengthened surveillance of CVD and stroke events, determination of the cost-effectiveness of policy interventions, and measurement of the extent to which vulnerable populations are reached must be assessed for all policies. Additional attention should be paid to the social determinants of health outcomes. CONCLUSIONS: AHA's public policies are generally robust and well aligned with its 2020 CVH metrics and CVD indicators. Areas for further policy development to fill gaps, overarching research strategies, and topic-specific priority areas are proposed.

Effectiveness and Safety of Apixaban, Dabigatran, and Rivaroxaban Versus Warfarin in Patients With Nonvalvular Atrial Fibrillation and Previous Stroke or Transient Ischemic Attack.

BACKGROUND AND PURPOSE: Limited real-world data exist comparing each non-vitamin K antagonist oral anticoagulant (NOAC) to warfarin in patients with nonvalvular atrial fibrillation who have had a previous ischemic stroke or transient ischemic attack. METHODS: Using MarketScan claims from January 2012 to June 2015, we identified adults newly initiated on oral anticoagulation, with ≥2 diagnosis codes for nonvalvular atrial fibrillation, a history of previous ischemic stroke/transient ischemic attack, and ≥180 days of continuous medical and prescription benefits before anticoagulation initiation. Three analyses were performed comparing 1:1 propensity score-matched cohorts of apixaban versus warfarin (n=2514), dabigatran versus warfarin (n=1962), and rivaroxaban versus warfarin (n=5208). Patients were followed until occurrence of a combined end point of ischemic stroke and intracranial hemorrhage (ICH) or major bleed, switch/discontinuation of index oral anticoagulation, insurance disenrollment, or end of follow-up. Mean follow-up was 0.5 to 0.6 years for all matched cohorts. RESULTS: Using Cox regression, neither apixaban nor dabigatran reduced the combined primary end point of ischemic stroke or ICH (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.33-1.48 and HR, 0.53; 95% CI, 0.26-1.07) and had nonsignificant effect on hazards of major bleeding (HR, 0.79; 95% CI, 0.38-1.64 and HR, 0.58; 95% CI, 0.26-1.27) versus warfarin. Rivaroxaban reduced the combined end point of ischemic stroke or ICH (HR, 0.45; 95% CI, 0.29-0.72) without an effect on major bleeding (HR, 1.07; 95% CI, 0.71-1.61). ICH occurred at rates of 0.16 to 0.61 events per 100 person-years in the 3 NOAC analyses, with no significant difference for any NOAC versus warfarin. CONCLUSIONS: Results from our study of the 3 NOACs versus warfarin in nonvalvular atrial fibrillation patients with a previous history of stroke/transient ischemic attack are relatively consistent with their respective phase III trials and previous stroke/transient ischemic attack subgroup analyses. All NOACs seemed no worse than warfarin in respect to ischemic stroke, ICH, or major bleeding risk.

A history of stroke/transient ischemic attack indicates high risks of cardiovascular event and hemorrhagic stroke in patients with coronary artery disease.

BACKGROUND: Randomized trials of antithrombotics in coronary artery disease have identified previous stroke/transient ischemic attack (TIA) as a marker of increased intracranial bleeding risk. We aimed to further characterize the risk of ischemic and bleeding events associated with a history of stroke/TIA in patients with coronary artery disease. METHODS AND RESULTS: From the international REduction of Atherothrombosis for Continued Health (REACH) registry of atherothrombosis, baseline characteristics and 4-year follow-up of 26,389 patients with coronary artery disease, including 4460 patients (16.9%) with a history of stroke/TIA, were analyzed. Patients with previous stroke/TIA had a higher rate of recurrent cardiovascular events (cardiovascular death, myocardial infarction, or stroke) than patients without (adjusted hazard ratio [HR], 1.52; 95% confidence interval [CI], 1.40-1.65; P<0.001) and specifically of nonfatal ischemic stroke (adjusted HR, 3.06; 95% CI, 2.62-3.57; P<0.001) and nonfatal hemorrhagic stroke rates (adjusted HR, 1.76; 95% CI, 1.00-3.08; P=0.05). Excess risk for nonfatal hemorrhagic stroke appeared confined to the 1st year after a stroke/TIA (adjusted HR, 3.03; 95% CI, 1.51-6.08 for the first year) and was particularly high in patients receiving dual antiplatelet therapy (adjusted HR, 5.21; 95% CI, 1.24-21.90). CONCLUSIONS: In patients with coronary artery disease, a history of stroke/TIA is associated with an independent increase in risk of death, myocardial infarction, or stroke, including both ischemic and hemorrhagic stroke (the latter being smaller in absolute terms). This excess risk of hemorrhagic stroke is particularly high in patients receiving dual antiplatelet therapy and in the 1st year after stroke/TIA. This observation is important for selection of antithrombotic therapy in these patients.

Stroke outcomes measures must be appropriately risk adjusted to ensure quality care of patients: a presidential advisory from the American Heart Association/American Stroke Association.

Because stroke is among the leading causes of death, disability, hospitalizations, and healthcare expenditures in the United States, there is interest in reporting outcomes for patients hospitalized with acute ischemic stroke. The American Heart Association/American Stroke Association, as part of its commitment to promote high-quality, evidence-based care for cardiovascular and stroke patients, fully supports the development of properly risk-adjusted outcome measures for stroke. To accurately assess and report hospital-level outcomes, adequate risk adjustment for case mix is essential. During the development of the Centers for Medicare & Medicaid Services 30-day stroke mortality and 30-day stroke readmission measures, concerns were expressed that these measures were not adequately designed because they do not include a valid initial stroke severity measure, such as the National Institutes of Health Stroke Scale. These outcome measures, as currently constructed, may be prone to mischaracterizing the quality of stroke care being delivered by hospitals and may ultimately harm acute ischemic stroke patients. This article details (1) why the Centers for Medicare & Medicaid Services acute ischemic stroke outcome measures in their present form may not provide adequate risk adjustment, (2) why the measures as currently designed may lead to inaccurate representation of hospital performance and have the potential for serious unintended consequences, (3) what activities the American Heart Association/American Stroke Association has engaged in to highlight these concerns to the Centers for Medicare & Medicaid Services and other interested parties, and (4) alternative approaches and opportunities that should be considered for more accurately risk-adjusting 30-day outcomes measures in patients with ischemic stroke.

Efficacy and safety of novel oral anticoagulants in patients with cervical artery dissections.

BACKGROUND: American and European guidelines support antiplatelet agents and anticoagulants as reasonable treatments of cervical artery dissection (CAD), though randomized clinical trials are lacking. The utility of novel oral anticoagulants (NOAC), effective in reducing embolic stroke risk in non-valvular atrial fibrillation (NVAF), has not been reported in patients with CAD. We report on the use, safety, and efficacy of NOACs in the treatment of CAD. METHODS: We retrospectively identified patients diagnosed with CAD at a single academic center between January 2010 and August 2013. Patients were categorized by their antithrombotic treatment at hospital discharge with a NOAC (dabigatran, rivaroxaban, or apixaban), traditional anticoagulant (AC: warfarin or treatment dose low-molecular weight heparin), or antiplatelet agent (AP: aspirin, clopidogrel, or aspirin/extended-release dypyridamole). Using appropriate tests, we compared the baseline medical history, presenting clinical symptoms and initial radiographic characteristics among patients in the 3 treatment groups. We then evaluated for the following outcomes: recurrent stroke, vessel recanalization, and bleeding complications. p values <0.05 were considered significant. RESULTS: Of the 149 included patients (mean age 43.4 years; 63.1% female; 70.5% vertebral artery CAD), 39 (26.2%), 70 (47.0%), and 40 (26.8%) were treated with a NOAC, AC, and AP, respectively. More patients with severe stenosis or occlusion were treated with NOAC than with AC or AP (61.8 vs. 60.0 vs. 22.5%, p = 0.002). Other baseline clinical and radiographic findings, including the presence of acute infarction and hematoma, did not differ between the 3 treatment groups. One hundred and thirty-five (90.6%) patients had clinical follow-up (median time 7.5 months) and 125 (83.9%) had radiographic follow-up (median time 5 months) information. There were 2 recurrent strokes in the NOAC group and 1 in each of the AC and AP groups (p = 0.822). There were more major hemorrhagic events in the AC group (11.4%) compared to the NOAC (0.0%) and AP (2.5%) groups (p = 0.034). Three patients treated with NOAC and none treated with AC or AP had a worsened degree of stenosis on follow-up imaging (8.6 vs. 0.0 vs. 0.0%, p = 0.019). CONCLUSION: Compared to traditional anticoagulants for CAD, treatment with NOACs is associated with similar rates of recurrent stroke, fewer hemorrhagic complications, but greater rates of radiographic worsening. These data suggest that NOACs may be a reasonable alternative in the management of CAD. Prospective validation of these findings is needed.