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Recent advances in therapy and the promulgation of multidisciplinary pulmonary embolism teams show great promise to improve management and outcomes of acute pulmonary embolism (PE). However, the absence of randomized evidence and lack of consensus leads to tremendous variations in treatment and compromises the wide implementation of new innovations. Moreover, the changing landscape of health care, where quality, cost, and accountability are increasingly relevant, dictates that a broad spectrum of outcomes of care must be routinely monitored to fully capture the impact of modern PE treatment. We set out to standardize data collection in patients with PE undergoing evaluation and treatment, and thus establish the foundation for an expanding evidence base that will address gaps in evidence and inform future care for acute PE. To do so, >100 international PE thought leaders convened in Washington, DC, in April 2022 to form the Pulmonary Embolism Research Collaborative. Participants included physician experts, key members of the US Food and Drug Administration, patient representatives, and industry leaders. Recognizing the multidisciplinary nature of PE care, the Pulmonary Embolism Research Collaborative was created with representative experts from stakeholder medical subspecialties, including cardiology, pulmonology, vascular medicine, critical care, hematology, cardiac surgery, emergency medicine, hospital medicine, and pharmacology. A list of critical evidence gaps was composed with a matching comprehensive set of standardized data elements; these data points will provide a foundation for productive research, knowledge enhancement, and advancement of clinical care within the field of acute PE, and contribute to answering urgent unmet needs in PE management. Evidence produced through the Pulmonary Embolism Research Collaborative, as it is applied to data collection, promises to provide crucial knowledge that will ultimately produce a robust evidence base that will lead to standardization and harmonization of PE management and improved outcomes. [ABSTRACT FROM AUTHOR]

Venous thrombosis and pulmonary embolism (venous thromboembolism) are important causes of morbidity and mortality worldwide. In patients with venous thromboembolism, thrombi obstruct blood vessels and resist physiological dissolution (fibrinolysis), which can be life threatening and cause chronic complications. Plasminogen activator therapy, which was developed >50 years ago, is effective in dissolving thrombi but has unacceptable bleeding risks. Safe dissolution of thrombi in patients with venous thromboembolism has been elusive despite multiple innovations in plasminogen activator design and catheter-based therapy. Evidence now suggests that fibrinolysis is rigidly controlled by endogenous fibrinolysis inhibitors, including α2-antiplasmin, plasminogen activator inhibitor-1, and thrombin-activable fibrinolysis inhibitor. Elevated levels of these fibrinolysis inhibitors are associated with an increased risk of venous thromboembolism in humans. New therapeutic paradigms suggest that accelerated and effective fibrinolysis may be achieved safely by therapeutically targeting these fibrinolytic inhibitors in venous thromboembolism. In this article, we discuss the role of fibrinolytic components in venous thromboembolism and the current status of research and development targeting fibrinolysis inhibitors. [ABSTRACT FROM AUTHOR]

BACKGROUND: Surgery or fibrinolysis is the currently available evidence-based treatment for obstructive mechanical valve thrombus. We reported the feasibility and short-term outcomes of percutaneous transcatheter therapy with cerebral embolic protection. Mid- and long-term outcomes remain unknown. METHODS: From 2020 to 2023, 24 patients underwent percutaneous transcatheter release of stuck leaflets with cerebral embolic protection for obstructive mitral mechanical valve thrombus. The indications for the transcatheter therapy were failed fibrinolysis, contraindications for fibrinolysis, not willing for fibrinolysis, or high risk for surgery. The study participants were followed up for a median period of 344.50 (65.00-953.75) days. RESULTS: Technical success was achieved in 91.67% (n=22) of procedures. During the follow-up, 12.50% (n=3) all-cause death, 4.17% (n=1) stroke, and 16.67% (n=4) recurrence were seen. The mean survival time free from death was 1101.48 (95% CI, 929.49-1273.47) days, stroke was 1211.38 (95% CI, 1110.40-1312.35) days, and recurrence was 907.71 (95% CI, 760.20-1055.21) days. CONCLUSIONS: Transcatheter release of the stuck mitral mechanical valve with cerebral embolic protection is an alternative therapy with promising mid-term outcomes where surgery or fibrinolysis is not possible or in failed fibrinolysis subsets. [ABSTRACT FROM AUTHOR]

The article discusses the use of thrombolysis in the treatment of acute pulmonary embolism (PE). Thrombolysis is a treatment that involves the use of medication to dissolve blood clots. The article highlights the importance of considering the volume and distribution of the embolism, as well as the functional reserve of the right ventricle, in determining the outcome of acute PE. The study evaluated the safety and efficacy of full-dose and reduced-dose thrombolysis using electronic health data from 16 hospitals. The results showed that bleeding events were less frequent in the real-world setting compared to controlled clinical trials, and outcomes were similar between the two dosing regimens. However, the study has limitations and leaves many questions unanswered. Overall, the authors suggest that clinicians should consider thrombolysis more readily in patients with acute intermediate high-risk PE, as reduced-dose thrombolysis has similar efficacy to full-dose thrombolysis with fewer hemorrhagic complications. [Extracted from the article]

Patients who develop an intracerebral hemorrhage (ICH) following thrombolysis in acute ischemic stroke (AIS) have a mortality rate as high as 50%. Treatment options include blood products, such as cryoprecipitate, or antifibrinolytics, such as tranexamic acid (TXA) or e-aminocaproic acid (EACA). Current guidelines recommend cryoprecipitate first-line despite limited data to support one agent over another. In addition, compared to antifibrinolytics, cryoprecipitate is higher in cost and requires thawing before use. This case series seeks to characterize the management of thrombolytic reversal at a single institution as well as provide additional evidence for antifibrinolytics in this setting. Patients were included for a retrospective review if they met the following criteria: presented between January 2011-January 2017, were >18 years of age, were admitted for AIS, received a thrombolytic, and received TXA EACA, or cryoprecipitate. Twelve patients met the inclusion criteria. Ten (83.3%) developed an ICH, one (8.3%) experienced gastrointestinal bleeding, and one (8.3%) had bleeding at the site of knee arthroscopy. Eleven patients received cryoprecipitate (median dose: 10 units), three received TXA (median dose: 1,000 mg), and one patient received EACA (13 g). TXA was administered faster than the first blood product at a mean time of 19 min and 137 min, respectively. Hemorrhagic expansion (N = 8, 66.67%) and inhospital mortality (N = 7, 58.3%) were high. While limited by its small sample size, this case series demonstrates significant variability in reversal strategies for thrombolysis-associated bleeding. It also provides additional evidence for the role of antifibrinolytics in this setting. [ABSTRACT FROM AUTHOR]

Background: Coronary artery disease (CAD) is the leading cause of cardiovascular morbidity, mortality, and healthcare costs in the United States. There are few reports on how public health and payment reforms might have influenced inpatient hospital use among patients with CAD. Objective: This study describes trends in hospital discharges, hospital charges, and discharge destinations in a national sample of patientswith CAD between 1997 and 2014.Methods: This was a longitudinal study with descriptive analysis of the Healthcare Cost and Utilization Project of National Inpatient Sample data. Findings: During this study period, the total number of discharges was 1333996. Patients with CAD between 65 and 84 years old were among the highest users of inpatient hospital services, followed by those in the 45- to 64-year age group. The death rate increased from 5961 to 7217 per 10000 patients during this time. The mean charge increased more than 5 times, from $9100 to $49643. There was a large difference in mean hospital charges in urban ($51666) and rural ($25548) locations in 2014. Coronary artery disease patientswith private insurance paidmore than those with Medicaid and Medicare plans. The discharge to home and healthcare costs increased by 4.1%and 4. 8%, respectively. Conclusion and Implications: Future researchers should use data sets, such as Medicare claims/Medical Expenditure Panel Study, that can provide comprehensive insights into patient-level factors influencing the use of inpatient care services among patients with CAD. Healthcare providers in posthospital settings should be well skilled in providing advanced cardiac rehabilitation and education to patients with CAD. [ABSTRACT FROM AUTHOR]

BACKGROUND: Rivaroxaban plus aspirin compared with aspirin alone reduced major cardiac and ischemic limb events after lower extremity revascularization (LER) in the VOYAGER PAD (Vascular Outcomes Study of ASA Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for Peripheral Artery Disease) trial. The effect has not been described in patients undergoing endovascular LER. METHODS: The VOYAGER PAD trial randomized 6564 patients with symptomatic peripheral artery disease to a double-blinded treatment with 2.5 mg of rivaroxaban BID or matching placebo and 100 mg of aspirin daily. The primary efficacy outcome was a composite of acute limb ischemia, major amputation of a vascular pathogenesis, myocardial infarction, ischemic stroke, or cardiovascular death. The principal safety end point was Thrombolysis in Myocardial Infarction major bleeding. A prespecified subgroup of patients who underwent endovascular revascularization was included. RESULTS: Endovascular LER occurred in 4379 (66.7%) patients and surgical LER in 2185 (33.3%). Over a 3-year follow-up, rivaroxaban reduced the risk of the primary outcome by 15% (hazard ratio [HR], 0.85 [95% CI, 0.76–0.96]) with an absolute risk reduction of 0.92% at 6 months and 1.04% at 3 years and a consistent benefit in those receiving endovascular (HR, 0.89 [95% CI, 0.76–1.03]) or surgical LER (HR, 0.81 [95% CI, 0.67–0.98]; P interaction=0.43). For endovascular-treated patients, rivaroxaban reduced the risk of acute limb ischemia or major amputation of a vascular pathogenesis by 30% (HR, 0.70 [95% CI, 0.54–0.90]; P =0.005) with an absolute risk reduction of 1.0% at 6 months and 2.0% at 3 years compared with aspirin alone. Among endovascular-treated patients, the median duration of concomitant dual antiplatelet therapy with clopidogrel treatment was 31 days (interquartile range, 30–58). There was a consistent benefit for rivaroxaban regardless of background clopidogrel. Thrombolysis in Myocardial Infarction major bleeding was significantly higher for the rivaroxaban and aspirin group for the endovascular cohort (HR, 1.66 [95% CI, 1.06–2.59]) with an absolute risk increase of 0.9% at 3 years with no increase in intracranial or fatal bleeding observed (HR, 0.86 [95% CI, 0.40–1.87]; P =0.71). Mortality with rivaroxaban was higher in the endovascular-treated patients (HR, 1.24 [95% CI, 1.02–1.52]), although this finding was isolated to specific regions. CONCLUSIONS: Rivaroxaban added to aspirin or dual antiplatelet therapy after LER for peripheral artery disease reduces ischemic risk and increases major bleeding without an increased risk of intracranial or fatal bleeding. These benefits are consistent in those treated with endovascular and surgical approaches with significant benefits for major adverse limb events. These data support the use of rivaroxaban in addition to aspirin or dual antiplatelet therapy after endovascular intervention for symptomatic peripheral artery disease. [ABSTRACT FROM AUTHOR]

BACKGROUND: ST-segment-elevation myocardial infarction (STEMI) guidelines recommend pharmaco-invasive treatment if timely primary percutaneous coronary intervention (PCI) is unavailable. Full-dose tenecteplase is associated with an increased risk of intracranial hemorrhage in older patients. Whether pharmaco-invasive treatment with half-dose tenecteplase is effective and safe in older patients with STEMI is unknown. METHODS: STREAM-2 (Strategic Reperfusion in Elderly Patients Early After Myocardial Infarction) was an investigatorinitiated, open-label, randomized, multicenter study. Patients =60 years of age with =2 mm ST-segment elevation in 2 contiguous leads, unable to undergo primary PCI within 1 hour, were randomly assigned (2:1) to half-dose tenecteplase followed by coronary angiography and PCI (if indicated) 6 to 24 hours after randomization, or to primary PCI. Efficacy end points of primary interest were ST resolution and the 30-day composite of death, shock, heart failure, or reinfarction. Safety assessments included stroke and nonintracranial bleeding. RESULTS: Patients were assigned to pharmaco-invasive treatment (n=401) or primary PCI (n=203). Median times from randomization to tenecteplase or sheath insertion were 10 and 81 minutes, respectively. After last angiography, 85.2% of patients undergoing pharmaco-invasive treatment and 78.4% of patients undergoing primary PCI had =50% resolution of ST-segment elevation; their residual median sums of ST deviations were 4.5 versus 5.5 mm, respectively. Thrombolysis In Myocardial Infarction flow grade 3 at last angiography was ?87% in both groups. The composite clinical end point occurred in 12.8% (51/400) of patients undergoing pharmaco-invasive treatment and 13.3% (27/203) of patients undergoing primary PCI (relative risk, 0.96 [95% CI, 0.62-1.48]). Six intracranial hemorrhages occurred in the pharmaco-invasive arm (1.5%): 3 were protocol violations (excess anticoagulation in 2 and uncontrolled hypertension in 1). No intracranial bleeding occurred in the primary PCI arm. The incidence of major nonintracranial bleeding was low in both groups (<1.5%). CONCLUSIONS: Halving the dose of tenecteplase in a pharmaco-invasive strategy in this early-presenting, older STEMI population was associated with electrocardiographic changes that were at least comparable to those after primary PCI. Similar clinical efficacy and angiographic end points occurred in both treatment groups. The risk of intracranial hemorrhage was higher with half-dose tenecteplase than with primary PCI. If timely PCI is unavailable, this pharmaco-invasive strategy is a reasonable alternative, provided that contraindications to fibrinolysis are observed and excess anticoagulation is avoided. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

One of the potential complications of acute myocardial infarction is left ventricular thrombus (LVT). The incidence of LVT following acute myocardial infarction has decreased dramatically with early invasive reperfusion techniques or fibrinolysis. However, the risk of LVT formation remains significant and is associated with an increased risk of systemic embolism, stroke, cardiovascular events, and even death. Current guidelines indicate that dual antiplatelet therapy and anticoagulation therapy for at least 3 months can reduce the risk of these events. While vitamin K antagonist is the preferred oral anticoagulant, there is growing evidence to support the use of direct-acting oral anticoagulants in LVT management. Cardiac magnetic resonance has shown the highest diagnostic accuracy for LVT assessment, followed by echocardiography with contrast agents. This article serves as a general review of the pathophysiology, diagnosis, and management of LVT. [ABSTRACT FROM AUTHOR]

Background: Patients with acute ischemic stroke (AIS) receiving thrombolysis with good function at discharge are usually ignored. Their functional deterioration after discharge not only compromises the effectiveness of thrombolytic therapy but also reduces their long-term quality of life, which is not conducive to the advancement of medical healthcare and continuing care. Objective: The aims of this study were to explore the risk factors for poor 6-month function in patients with AIS receiving thrombolysis with good function at discharge and construct a novel nomogram model. Methods: This case-control study retrospectively analyzed the medical data of 149 patients with AIS receiving thrombolysis with good function at discharge from January 2017 to June 2019. Patients were divided into a poor function group (<3 points) and a good function group (≥3 points) according to their modified Rankin Scale scores at 6 months. Logistic regression was used to identify risk factors for poor 6-month function. A novel nomogram prediction model for poor 6-month function was constructed, and its prediction performance and concordance were evaluated. Results: Of 149 patients, 21 (14%) had poor 6-month function and 128 (86%) had good 6-month function. Multivariate regression analysis showed that physical inactivity, neutrophil count, cerebral small vessel disease score, and hospitalization days were independent risk factors for poor 6-month function. A regression model was established according to the multivariate analysis, and the area under the curve was 0.9363. The accuracy was 71.99%, the sensitivity was 78.83%, and the specificity was 70.26%. A nomogram model was constructed, and its concordance index was 0.836 after internal validation. Conclusion: The novel nomogram model facilitates risk prediction of poor 6-month function in patients with AIS receiving thrombolysis with good function at discharge and is helpful for making discharge plans. [ABSTRACT FROM AUTHOR]

Despite the many advances in cardiovascular medicine, decisions concerning the diagnosis, prevention, and treatment of left ventricular (LV) thrombus often remain challenging. There are only limited organizational guideline recommendations with regard to LV thrombus. Furthermore, management issues in current practice are increasingly complex, including concerns about adding oral anticoagulant therapy to dual antiplatelet therapy, the availability of direct oral anticoagulants as a potential alternative option to traditional vitamin K antagonists, and the use of diagnostic modalities such as cardiac magnetic resonance imaging, which has greater sensitivity for LV thrombus detection than echocardiography. Therefore, this American Heart Association scientific statement was commissioned with the goals of addressing 8 key clinical management questions related to LV thrombus, including the prevention and treatment after myocardial infarction, prevention and treatment in dilated cardiomyopathy, management of mural (laminated) thrombus, imaging of LV thrombus, direct oral anticoagulants as an alternative to warfarin, treatments other than oral anticoagulants for LV thrombus (eg, dual antiplatelet therapy, fibrinolysis, surgical excision), and the approach to persistent LV thrombus despite anticoagulation therapy. Practical management suggestions in the form of text, tables, and flow diagrams based on careful and critical review of actual study data as formulated by this multidisciplinary writing committee are given. [ABSTRACT FROM AUTHOR]

Ischemic stroke represents 87% of all strokes. As global initiatives move forward with stroke care, health care providers and institutions will be called on to deliver the most current evidence-based care. The American Heart Association/American Stroke Association (AHA/ASA) estimates that 795 000 strokes occur each year; 610 000 are new strokes, and 185 000 are recurrent strokes. Eighty-seven percent are ischemic strokes; the overall mortality rate from stroke was 273 000, which makes stroke the fifth leading cause of death and the leading cause of disability in the United States. Stroke costs the United States an estimated $34 billion each year. This article outlines a nursing intervention regarding the use of intravenous thrombolytic therapy for treating acute ischemic stroke, the risk factors related to IV-alteplase, best-practice protocols, and the nursing role in efforts to deliver safe care. The conclusion reveals the need for health care organizations to explore opportunities, continually inspire innovation at the bedside, highlight nursing's essential contribution to acute stroke care, and encourage publishing improvements in patient care and the nurse practice environment. [ABSTRACT FROM AUTHOR]

This study aimed to develop and validate a clinical risk model based on clinical factors to predict prognosis in patients with wake-up stroke (WUS) after multimodal magnetic resonance imaging combined with recombinant tissue plasminogen activator intravenous thrombolysis. The study enrolled 263 patients with WUS, who were divided into the training (n = 162) and validation cohorts (n = 101). In the training cohort, patients were stratified based on modified Rankin Scale (mRS) score at 90 days after thrombolysis, with mRS ≤ 2 indicating a good prognosis (n = 117), and mRS > 2 indicating a poor prognosis (n = 45). Multivariate regression analyses were employed to identify independent risk factors and develop clinical risk models. The performance and stability of the clinical risk model were evaluated using receiver operating characteristic analysis and Hosmer-Lemeshow test. The clinical risk nomogram was constructed based on this model, and evaluated using decision curve analyses. Patients with poor prognosis showed a higher proportion of hyperlipidemia and diabetes and showed a higher levels of National Institute of Health Stroke Scale (NIHSS) at admission, NIHSS at 24 hours, triglyceride, and total cholesterol. Diabetes (odds ratio [OR] = 3.823), hyperlipidemia (OR = 7.361), NIHSS at admission (OR = 5.399), NIHSS at 24 hours (OR = 2.869), triglyceride (OR = 13.790), and total cholesterol (OR = 9.719) were independent predictors of poor prognosis in patients with WUS. Hosmer-Lemeshow test showed that the clinical risk model had a good fit in the training (χ2 = 19.573, P = .726) and validation cohorts (χ2 = 19.573, P = .726). The clinical risk model had an area under the curve value of 0.929 (95% confidence interval, 0.886-0.978) in the training cohort and 0.948 (0.906-0.989) in the validation cohort. The decision curve analysis indicated clinical risk nomogram has application value. The clinical risk model can effectively predict WUS prognosis outcomes., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Patients with premorbid dementia have been generally excluded from trials of stroke therapies, and their dementia diagnosis may affect the care received. There are few data on the quality of stroke care and outcomes in these patients., Methods: We compared the quality of care and outcomes for acute ischemic stroke patients with versus without premorbid dementia using national data from the Get With The Guidelines-Stroke registry between July 1, 2020, and December 31, 2021. Process outcomes included receiving intravenous thrombolysis, endovascular thrombectomy, and additional national quality measures. Clinical outcomes included ambulatory status at discharge, discharge destination, and mortality. The analyses were adjusted for patient and hospital characteristics., Results: Among 609 350 patients with acute ischemic stroke, 29 751 of 546 407 (5.4%) had documented prestroke dementia (median age, 84 [interquartile range, 78-89]; 62.8% female). Patients with versus without premorbid dementia were more likely to arrive via emergency medical services (70.5% versus 46.8%) and had more severe strokes (median National Institutes of Health Stroke Scale score, 7 [interquartile range, 3-15] versus 3 [interquartile range, 1-8]). They were less likely to be admitted to a comprehensive stroke center (17.9% versus 22.7%; P <0.0001), to receive intravenous thrombolysis (9.6% versus 11.1%; adjusted odds ratio [aOR], 0.91 [95% CI, 0.87-0.95]) or endovascular thrombectomy (4.5% versus 7.4%; aOR, 0.62 [95% CI, 0.56-0.68]), attain each of the Get With The Guidelines-Stroke Achievement Measures and Quality Measures, or attain defect-free stroke care (92.0% versus 95.0%; aOR, 0.75 [95% CI, 0.71-0.78]). Patients with premorbid dementia had longer door-to-needle times (adjusted difference, 3.17 minutes [95% CI, 1.34-5.01]), lower odds of being discharged home (43.8% versus 60.1%; aOR, 0.96 [95% CI, 0.93-1.00]), and higher odds of being nonambulatory at discharge (25.8% versus 9.3%; aOR, 1.62 [95% CI, 1.54-1.69]), and of in-hospital mortality or hospice admission (23.3% versus 8.6%; aOR, 1.38 [95% CI, 1.32-1.43]). Symptomatic intracranial hemorrhage after intravenous thrombolysis/endovascular thrombectomy did not differ (5.3% versus 3.7%; aOR, 1.13 [95% CI, 0.97-1.31])., Conclusions: Patients with premorbid dementia experienced slightly poorer quality of stroke care across multiple measures, were less likely to receive acute stroke interventions, and had worse poststroke outcomes than patients without dementia in a large nationwide registry. Our findings underscore the need for concerted efforts to further improve care quality and outcomes in this population.

Background: Timely revascularization in acute arterial ischemic stroke (AIS) is paramount for optimal outcomes. However, factors causing treatment delays in pediatric AIS remain understudied. We investigated determinants affecting the time from symptom onset or last-known-well to the start of recanalization treatment in pediatric AIS., Methods: We conducted an ancillary analysis of the French KID-CLOT study (The National Retrospective Study of Recanalization Treatments in Pediatric Arterial Ischemic Stroke), considering patients with pediatric AIS receiving recanalization treatments (IV thrombolysis IVT and mechanical thrombectomy) from 2015 to 2018. The study assessed prehospital triage's impact, direct versus transferred admissions, and unit type (pediatric versus adult) on treatment delay and clinical outcomes using modified Rankin Scale at 1 year., Results: Among 68 patients (median age, 11 [IQR, 4-16]; initial PedNIHSS, 13 [IQR, 7-19]), treatment modalities were IVT (n=31), and mechanical thrombectomy (n=23), and IVT+mechanical thrombectomy (n=14). Prehospital triage significantly reduced last-known-well to treatment delay (overall, 229 versus 270 minutes; P =0.01), most notably for and mechanical thrombectomy ( P <0.001). There was no substantial delay difference between direct and transferred admissions, or between unit types, although a trend favored adult units (370.3 versus 436.73 minutes; P =0.06). Prehospital triage correlated with improved outcomes, with a shift to lower modified Rankin Scale scores ( P =0.021)., Conclusions: For pediatric AIS treated with reperfusion therapy, prehospital triage emerges as a pivotal factor in reducing treatment delays and enhancing outcomes. These findings underscore the need for a dedicated prehospital stroke protocol for children., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03887143., Competing Interests: None.

Objectives: Delays in acute stroke treatment lead to poor outcomes. Women can present with atypical stroke symptoms, are older at the time of stroke, and tend to be living alone, causing delays in pre-hospital diagnosis and seeking care. It is unclear if gender disparities in ED arrival and stroke assessment are compounded by gender differences after ED arrival. Therefore, we sought to identify if gender and marital status were associated with faster door-to-treatment (DTT) time., Methods: Our single-center stroke database was queried for adults presenting to ED with acute stroke between January 1, 2018 and January 30, 2023 treated with IV thrombolytics (IVT)+/- endovascular thrombectomy (EVT) and a known DTT time. The primary outcome was DTT (door-to-needle+door-to-puncture) time. Data collected includes the National Institutes of Health Stroke Scale (NIHSS) at presentation and discharge, gender, marital status, age, and intervention (IVT alone or IVT+/- EVT)., Results: Among 674 patients identified, 35 patients were excluded due to missing data. Of 639 patients (median age 66 y), 25%/18% of patients were married men/women, respectively, and 22%/35% were single men/women. Median DTN time, DTP time, and discharge NIHSS score were 36, 79, and 4 mins, respectively. On multivariable analysis, neither DTT time nor NIHSS score at discharge improved among married men relative to any other combination of gender and marital status., Conclusions: Gender differences in the knowledge of stroke warning signs and gender disparities in ED assessment did not translate into faster DTT time. More work is needed to find ways to accelerate stroke care after ED arrival., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Existing data suggested a rural-urban disparity in thrombolytic utilization for ischemic stroke. Here, we examined the use of guideline-recommended stroke care and outcomes in rural hospitals to identify targets for improvement., Methods: This retrospective cohort study included patients (aged ≥18 years) treated for acute ischemic stroke at Get With The Guidelines-Stroke hospitals from 2017 to 2019. Multivariable mixed-effect logistic regression was used to compare thrombolysis rates, speed of treatment, secondary stroke prevention metrics, and outcomes after adjusting for patient- and hospital-level characteristics and stroke severity., Results: Among the 1 127 607 patients admitted to Get With The Guidelines-Stroke hospitals in 2017 to 2019, 692 839 patients met the inclusion criteria. Patients who presented within 4.5 hours were less likely to receive thrombolysis in rural stroke centers compared with urban stroke centers (31.7% versus 43.5%; adjusted odds ratio [aOR], 0.72 [95% CI, 0.68-0.76]) but exceeded rural nonstroke centers (22.1%; aOR, 1.26 [95% CI, 1.15-1.37]). Rural stroke centers were less likely than urban stroke centers to achieve door-to-needle times of ≤45 minutes (33% versus 44.7%; aOR, 0.86 [95% CI, 0.76-0.96]) but more likely than rural nonstroke centers (aOR, 1.24 [95% CI, 1.04-1.49]). For secondary stroke prevention metrics, rural stroke centers were comparable to urban stroke centers but exceeded rural nonstroke centers (aOR of 1.66, 1.94, 2.44, 1.5, and 1.72, for antithrombotics within 48 hours of admission, antithrombotics at discharge, anticoagulation for atrial fibrillation/flutter, statin treatment, and smoking cessation, respectively). In-hospital mortality was similar between rural and urban stroke centers (aOR, 1.11 [95% CI, 0.99-1.24]) or nonstroke centers (aOR, 1.00 [95% CI, 0.84-1.18])., Conclusions: Rural hospitals had lower thrombolysis utilization and slower treatment times than urban hospitals. Rural stroke centers provided comparable secondary stroke prevention treatment to urban stroke centers and exceeded rural nonstroke centers. These results reveal important opportunities and specific targets for rural health equity interventions., Competing Interests: Dr Uchino served on data safety monitoring board for clinical trials sponsored by Genentech Inc and Evaheart Inc and as consultant for Abbott Laboratories Inc. Dr Dalton received research support from the National Institute on Aging. Dr Fonarow received research support from the Patient Centered Outcome Research Institute and National Institutes of Health and served as consultant for Abbott Pharmaceuticals, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Eli Lilly and Company, Jassen Pharmaceuticals, Medtronic, Merck, Novartis, and Pfizer. The other authors report no conflicts.

Thrombolytic therapies for acute ischemic stroke are widely available but only result in recanalization early enough, to be therapeutically useful, in 10% to 30% of cases. This large gap in treatment effectiveness could be filled by novel therapies that can increase the effectiveness of thrombus clearance without significantly increasing the risk of harm. This focused update will describe the current state of emerging adjuvant treatments for acute ischemic stroke reperfusion. We focus on new treatments that are designed to (1) target different components that make up a stroke thrombus, (2) enhance endogenous fibrinolytic systems, (3) reduce stagnant blood flow, and (4) improve recanalization of distal thrombi and postendovascular thrombectomy., Competing Interests: Dr Mistry reports compensation from American Heart Association, AbbVie, RAPID AI, and American Heart Association for consultant services; compensation from Silver Creek Pharmaceuticals Inc and Translational Sciences for other services; employment by University of Cincinnati; and grants from National Institutes of Health, Society of Vascular and Interventional Neurology, National Institute of Neurological Disorders and Stroke, Patient-Centered Outcomes Research Institute, and National Institutes of Health. Dr Hill reports grants from Boehringer Ingelheim, Canadian Institutes of Health Research, Medtronic, and NoNO Inc; employment by University of Calgary; stock options in Basking Bioscience LLC; and compensation from Brainsgate Ltd for consultant services. Dr Coutts reports employment by Hotchkiss Brain Institute, University of Calgary. Dr Nogueira reports compensation from Anaconda Biomed, Medtronic USA Inc, Cerenovus, Genentech, Viz-AI, Prolong Pharmaceuticals, Perfuze, Biogen Inc, Shanghai Wallaby, Brainomix, Hybernia, RapidPulse, Imperative Care, Corindus Inc, NeuroVasc Technologies Inc, Corindus Vascular Robotics, Vesalio, Cerebrotech, Astrocyte, Ceretrieve, Phenox Inc, Philips, Anaconda, and Stryker Corporation for consultant services; compensation from Synchron for data and safety monitoring services; stock options in Ceretrieve, Brainomix, Corindus Inc, Perfuze, Truvic, Viz-AI, Reist/Q?Apel Medical, Vesalio, Cerebrotech, and Viseon Inc; stock holdings in Piraeus Medical, Brain4Care, and Quantanosis AI; and grants from Stryker and Cerenovus. Dr Nguyen reports compensation from Brainomix and Aruna for consultant services; and compensation from American Stroke Association for other services. Dr Medcalf reports grants from National Health and Medical Research Council. Dr Broderick reports grants from Genentech to other; compensation from Brainsgate, F. Hoffmann-La Roche, Basking Bioscience, and Kroger Prescription Plans Inc for consultant services; and grants from Novo Nordisk to other. Dr De Meyer reports grants from KU Leuven and Research Foundation Flanders. The other authors report no conflicts.

This article discusses the advancements in stroke science and care since the establishment of the American Heart Association. It highlights key milestones in the field, such as the use of x-rays and contrast angiography to visualize cerebral arteries, the development of computerized tomography for brain imaging, and the discovery of the "ischemic penumbra." The article also emphasizes the importance of stroke prevention and acute therapy, including the efficacy of anticoagulation and carotid endarterectomy. It further explores the connections between heart, brain, body, and mind, and the chronic and progressive effects of stroke on neurological and non-neurological health. The article concludes by emphasizing the need for comprehensive care and vigilance about the effects of stroke on other organs. [Extracted from the article]

Background: It is unknown whether the direct oral anticoagulant edoxaban can reduce leaflet thrombosis and the accompanying cerebral thromboembolic risk after transcatheter aortic valve replacement. In addition, the causal relationship of subclinical leaflet thrombosis with cerebral thromboembolism and neurological or neurocognitive dysfunction remains unclear.Methods: We conducted a multicenter, open-label randomized trial comparing edoxaban with dual antiplatelet therapy (aspirin plus clopidogrel) in patients who had undergone successful transcatheter aortic valve replacement and did not have an indication for anticoagulation. The primary end point was an incidence of leaflet thrombosis on 4-dimensional computed tomography at 6 months. Key secondary end points were the number and volume of new cerebral lesions on brain magnetic resonance imaging and the serial changes of neurological and neurocognitive function between 6 months and immediately after transcatheter aortic valve replacement.Results: A total of 229 patients were included in the final intention-to-treat population. There was a trend toward a lower incidence of leaflet thrombosis in the edoxaban group compared with the dual antiplatelet therapy group (9.8% versus 18.4%; absolute difference, -8.5% [95% CI, -17.8% to 0.8%]; P=0.076). The percentage of patients with new cerebral lesions on brain magnetic resonance imaging (edoxaban versus dual antiplatelet therapy, 25.0% versus 20.2%; difference, 4.8%; 95% CI, -6.4% to 16.0%) and median total new lesion number and volume were not different between the 2 groups. In addition, the percentages of patients with worsening of neurological and neurocognitive function were not different between the groups. The incidence of any or major bleeding events was not different between the 2 groups. We found no significant association between the presence or extent of leaflet thrombosis with new cerebral lesions and a change of neurological or neurocognitive function.Conclusions: In patients without an indication for long-term anticoagulation after successful transcatheter aortic valve replacement, the incidence of leaflet thrombosis was numerically lower with edoxaban than with dual antiplatelet therapy, but this was not statistically significant. The effects on new cerebral thromboembolism and neurological or neurocognitive function were also not different between the 2 groups. Because the study was underpowered, the results should be considered hypothesis generating, highlighting the need for further research.Registration: URL: https://www.Clinicaltrials: gov. Unique identifier: NCT03284827. [ABSTRACT FROM AUTHOR]

Acute pulmonary embolism (PE) is a potentially fatal condition that is often underdiagnosed due to its ambiguous and generalized symptoms. As such, nurse practitioners (NPs) may struggle to respond in a timely and accurate manner to clients presenting with acute PE. Given the complexities of diagnosing and managing PE, we propose a visual clinical care pathway to support NPs in recognizing and stratifying clients' risks of PE. The article provides guidance regarding PE diagnostic testing and offers a summary of effective, evidence-based treatment options for adult clients, including those with cancer. [ABSTRACT FROM AUTHOR]

Innovative catheter-based therapies are increasingly being used for the treatment of patients with submassive pulmonary embolism. These patients may be monitored in the intensive care unit following insertion of specialized pulmonary artery catheters. However, the infusion catheters utilized in catheter-based therapies differ greatly from traditional pulmonary artery catheters designed for hemodynamic monitoring. As such, the critical care team will have to be familiar with the monitoring and management of these novel catheters. Important distinctions between the catheters are illustrated using a clinical case report. [ABSTRACT FROM AUTHOR]

Background: Perfusion abnormalities in the infarct and salvaged penumbra have been proposed as a potential reason for poor clinical outcome (modified Rankin Scale score >2) despite complete angiographic reperfusion (Thrombolysis in Cerebral Infarction [TICI3]). In this study, we aimed to identify different microvascular perfusion patterns and their association with clinical outcomes among TICI3 patients., Methods: University Hospital Bern's stroke registry of all patients between February 2015 and December 2021. Macrovascular reperfusion was graded using the TICI scale. Microvascular reperfusion status was evaluated within the infarct area on cerebral blood volume and cerebral blood flow perfusion maps obtained 24-hour postintervention. Primary outcome was functional independence (90-day modified Rankin Scale score 0-2) evaluated with the logistic regression analysis adjusted for age, sex, and 24-hour infarct volume from follow-up imaging., Results: Based on microvascular perfusion findings, the entire cohort (N=248) was stratified into one of the 4 clusters: (1) normoperfusion (no perfusion abnormalities; n=143/248); (2) hyperperfusion (hyperperfusion on both cerebral blood volume and cerebral blood flow; n=54/248); (3) hypoperfusion (hypoperfusion on both cerebral blood volume and cerebral blood flow; n=14/248); and (4) mixed (discrepant findings, eg, cerebral blood volume hypoperfusion and cerebral blood flow hyperperfusion; n=37/248). Compared with the normoperfusion cluster, patients in the hypoperfusion cluster were less likely to achieve functional independence (adjusted odds ratio, 0.3 [95% CI, 0.1-0.9]), while patients in the hyperperfusion cluster tended to have better outcomes (adjusted odds ratio, 3.3 [95% CI, 1.3-8.8])., Conclusions: In around half of TICI3 patients, perfusion abnormalities on the microvascular level can be observed. Microvascular hypoperfusion, despite complete macrovascular reperfusion, is rare but may explain the poor clinical course among some TICI3 patients, while a detrimental effect of hyperperfusion after reperfusion could not be confirmed.

Competing Interests: Dr Simonsen reports grants from the Health Research Foundation of Central Denmark Region and speaker fee from Pfizer, outside the submitted work. Dr Blauenfeldt reports speaker fee from Novo Nordisk, Pfizer, and Bayer, outside the submitted work.

Background: The dramatic clinical improvement offered by mechanical thrombectomy raised questions about the relevance of prior intravenous thrombolysis in large-vessel occlusion strokes. Hence, studying intravenous thrombolysis susceptibility and its dependence on thrombus composition is crucial. We used an observational proteomic study of whole thrombi retrieved by mechanical thrombectomy to identify factors associated with fibrin content and fibrinolytic activity (FA)., Methods: In 104 stroke patients, the thrombi proteome was established by mass spectrometry coupled to liquid chromatography. FA was estimated in clots both outside (FA out ) by measuring D-dimer levels at the blood-thrombus interface and inside (FA in ) by evaluating the ratio of fibrinogen α to its plasmin-cleaved forms using proteomics coupled with protein electrophoresis. The factors associated with fibrin content, FA in , and FA out were determined by intravenous thrombolysis-adjusted linear regression., Results: FA out ( P <0.0001) and FA in ( P =0.0147) were driven by recombinant tissue-type plasminogen activator (r-tPA) administration (47/104) and thrombus composition. Indeed, FA out was greater with fibrin-rich than erythrocyte-rich thrombi, presumably because of more (r)tPA substrates. Thus, FA out was increased with cardioembolic thrombi (72/104), which are rich in fibrin ( P =0.0300). Opposite results were found inside the thrombus, suggesting that (r)tPA penetrability was hampered by the density of the fibrinous cap. Moreover, blood cells had a strong impact on thrombus structure and susceptibility to (r)tPA. Indeed, fibrin content was negatively associated with erythrocyte-specific proteins in the thrombus, admission hematocrit ( P =0.0139), and hemoglobin level ( P =0.0080), which underlines the key role of erythrocytes in thrombus composition. Also, an increased number of neutrophils impaired FA out ( P =0.0225), which suggests that their aggregation around the thrombus prevented the (r)tPA attack. Only FA out was significantly associated with reduced thrombus weight ( P =0.0310), increased recanalization rate ( P =0.0150), good clinical outcome ( P =0.0480), and reduced mortality ( P =0.0080)., Conclusions: Proteomics can offer new insights into the close relationship between thrombus composition and susceptibility to fibrinolysis, paving the way for new adjuvant therapies., Competing Interests: Disclosures None.

Abstract: This study seeks to identify the anticoagulant efficacy of rivaroxaban treatment on thrombi detected using echocardiography of the left atrial appendage in 275 patients with persistent atrial fibrillation. During follow-up after 9-24 weeks of rivaroxaban treatment, patients were divided into "effective group" (n = 143) and "ineffective group" (n = 132) according to the thrombolytic effect of the drug. Left atrial diameter (LAD), left atrial ejection fraction (LAEF), left ventricular ejection fraction (LVEF), mean diameter of left atrial appendage (LAAD mean ), angle between left atrial appendage and left atrium (LAA-A), velocity of blood flow in left atrial appendage (LAA-v), and thrombus size were compared before and after drug administration. Following treatment, LAEF, LVEF, and LAA-v values were greater and LAD and LAAD mean values were lower in the effective ( P < 0.05). Logistic regression analysis showed significant correlations of LAD, LAEF, LVEF, LAA-A, and LAA-v with anticoagulant efficacy ( P < 0.05). The efficacy of rivaroxaban in treatment of left atrial auricular thrombosis in patients with persistent AF was correlated with LAD, LAEF, LVEF, LAA-A, and LAA-v. Multivariate logistic regression analysis further revealed LAEF [odds ratio (OR) 1.7, 95% confidence interval (CI), 0.45-16.9, P = 0.008], 3D-EF (OR 6.4, 95% CI, 1.06-16.9, P = 0.039) and left ventricular global longitudinal strain (OR 18.0, 95% CI, 1.38-35.68, P = 0.028) as factors related to left atrial appendage thrombus. Echocardiography with global longitudinal strain assessment could be effectively utilized to evaluate the functional parameters of LAA and thus aid in predicting the safety of rivaroxaban as an anticoagulation agent., Competing Interests: The authors report no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Studies comparing bridging intravenous thrombolysis (IVT) with direct endovascular therapy (EVT) in patients with acute ischemic stroke who present late are limited. We aimed to compare the clinical outcomes and safety of bridging IVT in patients with acute ischemic stroke due to anterior circulation large vessel occlusion who underwent EVT 6 to 24 hours after time last known well., Methods: We enrolled patients with anterior circulation large vessel occlusion stroke and a National Institutes of Health Stroke Scale score of ≥6 from 20 centers across 10 countries in the multicenter retrospective CLEAR study (CT for Late Endovascular Reperfusion) between January 2014 and May 2022. We used inverse probability of treatment weighting modeling adjusted for clinical and imaging confounders to compare functional outcomes, reperfusion success, symptomatic intracranial hemorrhage, and mortality between EVT patients with and without prior IVT., Results: Of 5098 patients screened for eligibility, we included 2749 patients, of whom 549 received bridging IVT before EVT. The timing of IVT was not recorded. Witnessed stroke onset and transfer rates were higher in the bridging IVT group (25% versus 12% and 77% versus 55%, respectively, P value for both <0.0001), and time intervals between stroke onset and treatment were shorter (time last known well-start of EVT median 560 minutes [interquartile range, 432-791] versus 724 minutes [interquartile range, 544-912]; P <0.0001). After adjustment for confounders, there was no difference in functional outcome at 3 months (adjusted common odds ratio for modified Rankin Scale shift, 1.03 [95% CI, 0.89-1.19]; P =0.72) or successful reperfusion (adjusted odds ratio, 1.19 [95% CI, 0.81-1.75]; P =0.39). There were no safety concerns associated with bridging IVT versus direct EVT (symptomatic intracranial hemorrhage: adjusted odds ratio, 0.75 [95% CI, 0.38-1.48]; P =0.40; mortality: adjusted odds ratio, 1.14 [95% CI, 0.89-1.46]; P =0.31). Results were unchanged when the analysis was limited to patients who received IVT >6 hours after last known well., Conclusions: In patients with an anterior circulation large vessel occlusion stroke who underwent EVT 6 to 24 hours from last known well, bridging IVT was not associated with a difference in outcomes compared with direct EVT., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04096248., Competing Interests: Disclosures Drs Demeestere and Lemmens reported institutional research fees from Genentech. Dr Strbian reported consultancy fees from AstraZeneca and Boehringer Ingelheim. Dr Nogueira reported consultancy for Biogen, Brainomix, Corindus, Cerenovus, Stryker, Medtronic, Ceretrieve, Anaconda, Biomed, Vesalio, Imperative Care, NeuroVasc Technologies, Viz AI, Genentech, Prolong Pharmaceuticals, Perfuze, Phenox, RapidPulse; stock options in Viz AI, Vesalio, Perfuze, Corindus, Brainomix, Ceretrieve; grants from Cerenovus and Stryker. Dr Nagel reported consultancy for Brainomix; speaker with Boehringer ingelheim and Pfizer. Dr Yamagami reported research grants from Bristol Myers Squibb; lecturer’s fees from Stryker, Medtronic, Johnson & Johnson, Bayer, Daiichi Sankyo, Bristol Myers Squibb, Otuska Pharmaceutical; advisory board for Daiichi Sankyo. Dr Puetz reported lecturer for Daiichi Sankyo. Dr Haussen reported consultancy for Vesalio, Cerenovus, Stryker, Brainomix, Poseydon Medical, and Chiesi USA; Data Safety and Monitoring Board from Jacobs Institute; and stock options in Viz AI. Dr Ribo reported consultancy for Medtronic, MiniMed, Cerenovus, AptaTargets, Stryker, Philips; stock holdings in Methinks, Nora, and Anaconda Biomed. Dr Michel reported grants from University of Lausanne and Swiss National Science Foundation (SNF). Dr Marto reported consulting from Amicus Therapeutics, Boehringer Ingelheim; Speaker with Boehringer Ingelheim. Dr Henon reported fees from Novartis and a grant from Sanofi-Aventis. Dr Gutierrez reported consultancy fees from Medtronic, Stryker and Microvention, and a grant from Methinks, Microvention, Stryker and the National Institutes of Health. Dr Siegler reported a grant from Philips and Viz AI. Dr Yoshimura reported research grants from Stryker, Siemens Healthineers, Bristol Myers Squibb, Sanofi, Eisai, Daiichi Sankyo, Teijin Pharma, Chugai Pharmaceutical, HEALIOS, Asahi Kasei Medical, Kowa, CSL Behring; lecturer fees from Stryker, Medtronic, Johnson & Johnson, Kaneka, Terumo, Biomedical Solutions, Boehringer Ingelheim, Daiichi Sankyo, Bayer and Bristol-Meyers Squibb. Dr Sheth reported consultancy for Imperative Care, Viz AI, Penumbra; compensation from Motif Neurosciences; grants from National Institutes of Health. Dr Dobrocky reported consultancy fees from MicroVention. Dr Kaesmacher reported grants from the Swiss Academy of Medical Sciences/Bangerter Foundation, Swiss Stroke Society, and Clinical Trials Unit Bern. Dr Zaidi reported a grant from Genentech. Dr Castonguay reported employment by Medtronic. Dr Uchida reported fees by Bristol Myers Squibb, Daiichi Sankyo, Medtronic and Stryker. Dr Sakai reported research grant from Biomedical Solutions, Medtronic, Terumo, TG Medical; lecturer’s fees from Asahi-Intec, Biomedical Solutions, Daiichi Sankyo, Kaneka, Medtronic, Terumo; advisory board for Johnson & Johnson, Medtronic, Terumo. Dr Toyoda reported lecturer fees from Otsuka, Daiichi Sankyo, Bayer, Novartis, and Bristol-Myers Squibb. Dr Kaiser reported grants from the Joachim Herz Foundation. Dr Möhlenbruch reported grants from Medtronic, Stryker, and MicroVention. Dr Ringleb reported travel support from Bayer and Bristol Myers Squibb; consultancy for Daiichi Sankyo Company and Boehringer Ingelheim. Dr Zaidat reported consultancy fees by Johnson & Johnson, Medtronic and Stryker, Penumbra stock, and a grant from Johson & Johnson, Medtronic, Penumbra and Stryker. Dr Fischer reported research support from SNF, Medtronic, Stryker, Rapid Medical, Penumbra, Phenox; consultancies for Stryker, CSL Behring; advisory board for Alexion/Portola, Boehringer Ingelheim, Biogen, Acthera. Dr Nguyen discloses research support from Medtronic to her institution; advisory board for Brainomix, Aruna Bio; Associate Editor Stroke.

Background: AST-004, a small molecule agonist of the adenosine A1 and A3 receptors, is a potential cerebroprotectant for patients with acute stroke and is currently in clinical trials. Drug-drug interactions are critically important to assess in the context of acute stroke care. Lytic therapy with tPA (tissue-type plasminogen activator)-induced plasmin formation (alteplase) is the only available pharmacotherapy for acute stroke. Consequently, it is imperative to evaluate potential interactions between AST-004 and tPAs such as alteplase and tenecteplase., Methods: The interactions between AST-004 and tPAs were evaluated in 3 ways in preparation for AST-004 phase II trials. First, the metabolic stability of AST-004 was determined in the presence of alteplase and plasmin. Second, the potential for AST-004 to influence the thrombolytic efficacy of alteplase and tenecteplase was evaluated with an in vitro assay system utilizing a fluorogenic substrate of plasmin. Finally, the potential for AST-004 to influence the thrombolytic efficacy of alteplase was also determined with an in vitro thrombolysis assay of human blood thrombi., Results: Neither alteplase nor plasmin affected the stability of AST-004 in vitro. In 2 different in vitro systems, AST-004 had no effect on the ability of alteplase or tenecteplase to generate plasmin, and AST-004 had no effect on the thrombolytic efficacy of alteplase to lyse blood clots in human blood., Conclusions: These studies indicate that there will be no interactions between AST-004 and tPAs such as alteplase or tenecteplase in patients with stroke undergoing thrombolytic therapy., Competing Interests: Disclosures Drs Liston and Korinek are employees of Astrocyte Pharmaceuticals Inc. Dr Lechleiter is a co-founder of Astrocyte Pharmaceuticals Inc, and a science advisor. D. Solt is an employee of Thrombodyne MDEC, LLC.

Background: Patients with acute ischemic stroke harboring a large vessel occlusion admitted to nonendovascular-capable centers often require interhospital transfer for thrombectomy. We evaluated the incidence and predictors of arterial recanalization during transfer, as well as the relationship between interhospital recanalization and clinical outcomes., Methods: We analyzed data from 2 cohorts of patients with an anterior circulation large vessel occlusion transferred for consideration of thrombectomy to a comprehensive center, with arterial imaging at the referring hospital and on comprehensive stroke center arrival. Interhospital recanalization was determined by comparison of the baseline and posttransfer arterial imaging and was defined as revised arterial occlusive lesion (rAOL) score 2b to 3. Pretransfer variables independently associated with interhospital recanalization were studied using multivariable logistic regression analysis., Results: Of the 520 included patients (Montpellier, France, n=237; Stanford, United States, n=283), 111 (21%) experienced interhospital recanalization (partial [rAOL=2b] in 77% and complete [rAOL=3] in 23%). Pretransfer variables independently associated with recanalization were intravenous thrombolysis (adjusted odds ratio, 6.8 [95% CI, 4.0-11.6]), more distal occlusions (intracranial carotid occlusion as reference: adjusted odds ratio, 2.0 [95% CI, 0.9-4.5] for proximal first segment of the middle cerebral artery, 5.1 [95% CI, 2.3-11.5] for distal first segment of the middle cerebral artery, and 5.0 [95% CI, 2.1-11.8] for second segment of the middle cerebral artery), and smaller clot burden (clot burden score 0-4 as reference: adjusted odds ratio, 3.4 [95% CI, 1.5-7.6] for 5-7 and 5.6 [95% CI, 2.4-12.7] for 8-9). Recanalization on arrival at the comprehensive center was associated with less interhospital infarct growth (rAOL, 0-2a: 11.6 mL; rAOL, 2b: 2.2 mL; rAOL, 3: 0.6 mL; P trend <0.001) and greater interhospital National Institutes of Health Stroke Scale score improvement (0 versus -5 versus -6; P trend <0.001). Interhospital recanalization was associated with reduced 3-month disability (adjusted common odds ratio, 2.51 [95% CI, 1.68-3.77]) with greater benefit from complete than partial recanalization., Conclusions: Recanalization is frequently observed during interhospital transfer for thrombectomy and is strongly associated with favorable outcomes, even when partial. Broadening thrombolysis indications in primary centers, and developing therapies that increase recanalization during transfer, will likely improve clinical outcomes., Competing Interests: Disclosures Dr Wouters reports grants from Remmert Adriaan-Laan-Fonds. Dr Arquizan reports compensation from Amgen and Medtronic Vascular, Inc, for other services. Dr Christensen reports stock holdings in iSchemaView. Dr Costalat reports compensation from Penumbra, Inc, MicroVention, Inc, Balt USA, LLC, Stryker Corporation, Medtronic USA, Inc, and Johnson & Johnson Health Care Systems, Inc, for consultant services. Dr Heit reports consulting fees from Medtronic and MicroVention, and he is a member of the Medical and Scientific Advisory Board of iSchemaView. Dr Albers reports stock holdings in iSchemaView and compensation from Biogen, iSchemaView, and Genentech for consultant services. The other authors report no conflicts.

Background: Current evidence provides limited support for the superiority of endovascular thrombectomy (EVT) in patients with M2 segment middle cerebral artery occlusion. We aim to investigate whether imaging features of M2 segment occlusion impact the effectiveness of EVT., Methods: We conducted a retrospective cohort study from January 2017 to January 2022, drawing data from the CASE II registry (Computer-Based Online Database of Acute Stroke Patients for Stroke Management Quality Evaluation), which specifically documented patients with acute ischemic stroke presenting with M2 segment occlusion undergoing reperfusion therapy. Patients were stratified into the intravenous thrombolysis (IVT) group (IVT alone) and EVT group (IVT plus EVT or EVT alone). The primary outcome was a modified Rankin Scale score 0 to 2 at 90 days. Secondary outcomes included additional thresholds and distribution of modified Rankin Scale scores, 24-hour recanalization, early neurological deterioration, and relevant complications during hospitalization. Safety outcomes encompassed intracranial hemorrhagic events at 24 hours and mortality at 90 days. Binary logistic regression analyses with propensity score matching were used. Subgroup analyses were performed based on the anatomic site of occlusion, including right versus left, proximal versus distal, dominant/co-dominant versus nondominant, single versus double/triple branch(es), and anterior versus central/posterior branch., Results: Among 734 patients (43.3% were females; median age, 73 years) with M2 segment occlusion, 342 (46.6%) were in the EVT group. Propensity score matching analysis revealed no statistical difference in the primary outcome (odds ratio, 0.860 [95% CI, 0.611-1.209]; P =0.385) between the EVT group and IVT group. However, EVT was associated with a higher incidence of subarachnoid hemorrhage (odds ratio, 6.655 [95% CI, 1.487-29.788]; P =0.004) and pneumonia (odds ratio, 2.015 [95% CI, 1.364-2.977]; P <0.001). Subgroup analyses indicated that patients in the IVT group achieved better outcomes when presenting with right, distal, or nondominant branch occlusion ( P all interaction <0.05)., Conclusions: Our study showed similar efficiency of EVT versus IVT alone in acute M2 segment middle cerebral artery occlusion. This suggested that only specific patient subpopulations might have a potentially higher benefit of EVT over IVT alone., Registration: URL: https://clinicaltrials.gov; Unique identifier: NCT04487340., Competing Interests: Disclosures None.

Objective: Documenting vital signs and National Institutes of Health Stroke Scale (NIHSS) once every 15 minutes after intravenous thrombolytic therapy for acute ischemic stroke is often used as a metric to assess the quality of care. This study explores the association between "once every 15 minutes" documentation and stroke outcomes. Methods: This is a retrospective study of the first 2 hours of vital signs and NIHSS documentation after thrombolytic stroke therapy. Sociodemographic and clinical data, including NIHSS, temperature, heart rate, systolic blood pressure, diastolic blood pressure, mean arterial blood pressure, and respiratory rate, were abstracted from the medical record. Missing documentation was examined for association with modified Rankin Scale (mRS) scores and neurologic changes. Result: Among 84 patients with a mean age of 68.8 years, there were 2276 documented assessments from an expected 3780. There were 104 clinically significant changes in 1 or more index variables. The most commonly missed documentation occurred during interventional radiology. After controlling for admission NIHSS, there was no significant relationship between the completeness of documentation and discharge mRS score (r² = 0.047, P = .0561), nor between vital sign documentation and discharge mRS (r² = 0.003, P = .6338). Conclusion: Frequency of documentation does not reflect the quality of care during the early phase of acute stroke treatment. [ABSTRACT FROM AUTHOR]

Stroke, the most common form of cerebrovascular disease, is a leading cause of death and disability throughout the world. There have been no significant advances in the development of effective therapeutics for hemorrhagic stroke, and for ischemic stroke highly effective, evidence-based therapies such as alteplase and mechanical thrombectomy are widely underutilized. Improving outcomes for patients experiencing ischemic stroke requires faster recognition and appropriate intervention within the treatment window (the first 24 hours after symptom onset). This article discusses the pathophysiology underlying the various types of ischemic stroke; the risk factors for ischemic stroke; stroke presentation; and the evidence-based treatments, nursing assessments, and monitoring protocols that are critical to patient recovery. [ABSTRACT FROM AUTHOR]

The article focuses on the management strategies for ST-segment elevation (STE)-acute coronary syndrome (ACS). Topics discussed include Persistent electrocardiographic (ECG) STE-ACS reflects an ongoing transmural myocardial ischemia and necrosis; and Acute care NPs are in an ideal position to diagnose and manage STE-ACS by implementing guideline-driven medical interventions.

Objective: Management of patients experiencing massive pulmonary embolism-related cardiac arrest is controversial. Venoarterial extracorporeal membranous oxygenation has emerged as a potential therapeutic option for these patients. We performed a systematic review assessing survival and predictors of mortality in patients with massive PE-related cardiac arrest with venoarterial extracorporeal membranous oxygenation use.Data Sources: A literature search was started on February 16, 2020, and completed on March 16, 2020, using PubMed, Embase, Cochrane Central, Cinahl, and Web of Science.Study Selection: We included all available literature that reported survival to discharge in patients managed with venoarterial extracorporeal membranous oxygenation for massive PE-related cardiac arrest.Data Extraction: We extracted patient characteristics, treatment details, and outcomes.Data Synthesis: About 301 patients were included in our systemic review from 77 selected articles (total screened, n = 1,115). About 183 out of 301 patients (61%) survived to discharge. Patients (n = 51) who received systemic thrombolysis prior to cannulation had similar survival compared with patients who did not (67% vs 61%, respectively; p = 0.48). There was no significant difference in risk of death if PE was the primary reason for admission or not (odds ratio, 1.62; p = 0.35) and if extracorporeal membranous oxygenation cannulation occurred in the emergency department versus other hospital locations (odds ratio, 2.52; p = 0.16). About 53 of 60 patients (88%) were neurologically intact at discharge or follow-up. Multivariate analysis demonstrated three-fold increase in the risk of death for patients greater than 65 years old (adjusted odds ratio, 3.08; p = 0.03) and six-fold increase if cannulation occurred during cardiopulmonary resuscitation (adjusted odds ratio, 5.67; p = 0.03).Conclusions: Venoarterial extracorporeal membranous oxygenation has an emerging role in the management of massive PE-related cardiac arrest with 61% survival. Systemic thrombolysis preceding venoarterial extracorporeal membranous oxygenation did not confer a statistically significant increase in risk of death, yet age greater than 65 and cannulation during cardiopulmonary resuscitation were associated with a three- and six-fold risks of death, respectively. [ABSTRACT FROM AUTHOR]

Background: PCSK9 (proprotein convertase subtilisin/kexin 9), mainly secreted by the liver and released into the blood, elevates plasma low-density lipoprotein cholesterol by degrading low-density lipoprotein receptor. Pleiotropic effects of PCSK9 beyond lipid metabolism have been shown. However, the direct effects of PCSK9 on platelet activation and thrombosis, and the underlying mechanisms, as well, still remain unclear.Methods: We detected the direct effects of PCSK9 on agonist-induced platelet aggregation, dense granule ATP release, integrin αIIbβ3 activation, α-granule release, spreading, and clot retraction. These studies were complemented by in vivo analysis of FeCl3-injured mouse mesenteric arteriole thrombosis. We also investigated the underlying mechanisms. Using the myocardial infarction (MI) model, we explored the effects of PCSK9 on microvascular obstruction and infarct expansion post-MI.Results: PCSK9 directly enhances agonist-induced platelet aggregation, dense granule ATP release, integrin αIIbβ3 activation, P-selectin release from α-granules, spreading, and clot retraction. In line, PCSK9 enhances in vivo thrombosis in a FeCl3-injured mesenteric arteriole thrombosis mouse model, whereas PCSK9 inhibitor evolocumab ameliorates its enhancing effects. Mechanism studies revealed that PCSK9 binds to platelet CD36 and thus activates Src kinase and MAPK (mitogen-activated protein kinase)-extracellular signal-regulated kinase 5 and c-Jun N-terminal kinase, increases the generation of reactive oxygen species, and activates the p38MAPK/cytosolic phospholipase A2/cyclooxygenase-1/thromboxane A2 signaling pathways downstream of CD36 to enhance platelet activation, as well. Using CD36 knockout mice, we showed that the enhancing effects of PCSK9 on platelet activation are CD36 dependent. It is important to note that aspirin consistently abolishes the enhancing effects of PCSK9 on platelet activation and in vivo thrombosis. Last, we showed that PCSK9 activating platelet CD36 aggravates microvascular obstruction and promotes MI expansion post-MI.Conclusions: PCSK9 in plasma directly enhances platelet activation and in vivo thrombosis, and MI expansion post-MI, as well, by binding to platelet CD36 and thus activating the downstream signaling pathways. PCSK9 inhibitors or aspirin abolish the enhancing effects of PCSK9, supporting the use of aspirin in patients with high plasma PCSK9 levels in addition to PCSK9 inhibitors to prevent thrombotic complications. [ABSTRACT FROM AUTHOR]

Background: Faster delivery of tPA (tissue-type plasminogen activator) results in better health outcomes for eligible patients with stroke. Standardization of stroke protocols in emergency departments (EDs) has been difficult, especially in nonstroke centers. We measured the effectiveness of a centrally led implementation strategy with local site tailoring to sustain adherence to an acute stroke protocol to improve door-to-needle (DTN) times across disparate EDs in a multihospital health system., Methods: Prospective, type III hybrid effectiveness-implementation cohort study measuring performance at 21 EDs in Utah and Idaho (stroke centers [4]/nonstroke centers [17]) from January 2018 to February 2020 using a nonrandomized stepped-wedge design, monthly repeated site measures and multilevel hierarchical modeling. Each site received the implementation strategies in 1 of 6 steps providing control and intervention data. Co-primary outcomes were percentage of DTN times ≤60 minutes and median DTN time. Secondary outcomes included percentage of door-to-activation of neurological consult times ≤10 minutes and clinical effectiveness outcomes. Results were stratified between stroke and nonstroke centers., Results: A total of 855 474 ED patient encounters occurred with 5325 code stroke activations (median age, 69 [IQR, 56-79] years; 51.8% female patients]. Percentage of door-to-activation times ≤10 minutes increased from 47.5% to 59.9% (adjusted odds ratio, 1.93 [95% CI, 1.40-2.67]). A total of 615 patients received tPA of ≤3 hours from symptom onset (median age, 71 [IQR, 58-80] years; 49.6% female patients). The percentage of DTN times ≤60 minutes increased from 72.5% to 86.1% (adjusted odds ratio, 3.38, [95% CI, 1.47-7.78]; stroke centers (77.4%-90.0%); nonstroke centers [59.3%-72.1%]). Median DTN time declined from 46 to 38 minutes (adjusted median difference, -9.68 [95% CI, -17.17 to -2.20]; stroke centers [41-35 minutes]; nonstroke centers [55-52 minutes]). No differences were observed in clinical effectiveness outcomes., Conclusions: A centrally led implementation strategy with local site tailoring led to faster delivery of tPA across disparate EDs in a multihospital system with no change in clinical effectiveness outcomes including rates of complication. Disparities in performance persisted between stroke and nonstroke centers., Competing Interests: Disclosures Dr McKee consults for Ceraxis Health, Inc, Drs Knighton and Püttgen own shares in large publicly traded health/biotechnology companies not affiliated with this research. Dr Srivastava is a founder of the I-PASS Patient Safety Institute in which his employer, Intermountain Health owns his equity. Dr Srivastava has received monetary awards, honorariums, and travel reimbursement from multiple academic and professional organizations for teaching about pediatric hospitalist research networks and quality of care. The other authors report no conflicts.

Competing Interests: Disclosure: The authors have no conflicts of interest to report.

Objective: We mainly explore the predictive value of Barthel Index (BI), SPAN-100, and National Institute of Health stroke scale (NIHSS) scores on clinical prognosis and functional outcomes in thrombolytic patients and compare the differences in the predictive values of the above 3 scales so as to provide an effective basis to evaluate the prognosis of thrombolytic patients., Methods: Data were collected from 212 patients with the first-onset AIS (acute ischemic stroke). The enrolled patients were treated with recombinant tissue plasminogen activator thrombolytic therapy and were divided into 2 groups according to the modified Rankin Scale (mRS) score at discharge: the prognosis group (mRS≤2 points) and the poor prognosis group (mRS≥3 points). Logistic multivariate analysis was used to analyze the predictors of poor prognosis in patients with thrombolysis. MedCalc software was used to plot receiver operating characteristic (ROC) curves, calculate the area under the ROC curve (AUC), and compare the prediction performance of the 3 scales by the Delong and colleagues' method, and the difference of P <0.05 was statistically significant., Results: Logistic binary regression multivariate analysis suggested that BI was a predictor of poor prognosis for thrombolytic therapy in patients with AIS. The lower the BI score, the poorer the prognosis. The AUC for BI score was 0.862, 95% CI (0.808-0.906), NIHSS score AUC was 0.665, 95% CI (0.597-0.728), and SPAN-100 score AUC was 0.640, 95% CI (0.572-0.705). AUC comparison of 3 scoring ROC curves suggested statistically significant differences between BI and NIHSS ( PC =0.0000), BI and SPAN-100 ( PC =0.0000); no significant difference was observed between SPAN-100 and NIHSS ( PC =1.7997)., Conclusions: Simple BI scores have a high prognostic value for thrombolytic therapy in AIS., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Resistance to r-tPA (recombinant tissue-type plasminogen activator) is a well-known but poorly understood phenomenon that hampers successful recanalization in patients with acute ischemic stroke. Using clinically relevant thrombi from patients with acute ischemic stroke, we investigated if and how thrombus composition impacts r-tPA-mediated lysis. In addition, we explored strategies to overcome r-tPA resistance., Methods: Thrombi were split into 2 parts, 1 of which was used for thrombolysis and the other for detailed histological analysis. Thrombolysis was performed in normal human plasma using r-tPA alone, using r-tPA in combination with DNase-1 or using r-tPA in combination with N,N'-diacetyl-l-cystine. Thrombus lysis was calculated as the percentage of residual thrombus weight compared with its initial weight and the degree of lysis was linked to thrombus composition determined via histology., Results: Interestingly, we found that the efficacy of r-tPA-mediated thrombolysis was strongly correlated with the composition of the thrombi. Thrombi containing high amounts of red blood cells and low amounts of DNA and von Willebrand Factor were efficiently degraded by r-tPA, whereas thrombi containing low amounts of red blood cells and higher amounts of DNA and von Willebrand Factor were resistant to r-tPA. Importantly, combination of r-tPA with DNase-1 or N,N'-diacetyl-l-cystine significantly and specifically improved the lysis of these r-tPA-resistant thrombi., Conclusions: Using patient thrombus material, our results for the first time show that the composition of stroke thrombi largely determines their susceptibility to r-tPA-mediated thrombolysis. Red blood cell-poor thrombi have a specific resistance to r-tPA, which can be overcome by targeting nonfibrin components using DNase-1 or N,N'-diacetyl-l-cystine., Competing Interests: Disclosures Dr François is a consultant for iVascular. Dr Vanacker received speaker fees from Boehringer-Ingelheim, BMS, Pfizer, Daiichi-Sankyo, and Medtronic. Dr Andersson holds equity for Cereflo Ltd and is a consultant for Anaconda, Cerenovus/Neuravi, Optimize Neurovascular and Rapid medical. The other authors report no conflicts.

Patients who develop an intracerebral hemorrhage (ICH) following thrombolysis in acute ischemic stroke (AIS) have a mortality rate as high as 50%. Treatment options include blood products, such as cryoprecipitate, or antifibrinolytics, such as tranexamic acid (TXA) or ε-aminocaproic acid (EACA). Current guidelines recommend cryoprecipitate first-line despite limited data to support one agent over another. In addition, compared to antifibrinolytics, cryoprecipitate is higher in cost and requires thawing before use. This case series seeks to characterize the management of thrombolytic reversal at a single institution as well as provide additional evidence for antifibrinolytics in this setting. Patients were included for a retrospective review if they met the following criteria: presented between January 2011-January 2017, were >18 years of age, were admitted for AIS, received a thrombolytic, and received TXA EACA, or cryoprecipitate. Twelve patients met the inclusion criteria. Ten (83.3%) developed an ICH, one (8.3%) experienced gastrointestinal bleeding, and one (8.3%) had bleeding at the site of knee arthroscopy. Eleven patients received cryoprecipitate (median dose: 10 units), three received TXA (median dose: 1,000 mg), and one patient received EACA (13 g). TXA was administered faster than the first blood product at a mean time of 19 min and 137 min, respectively. Hemorrhagic expansion (N = 8, 66.67%) and inhospital mortality (N = 7, 58.3%) were high. While limited by its small sample size, this case series demonstrates significant variability in reversal strategies for thrombolysis-associated bleeding. It also provides additional evidence for the role of antifibrinolytics in this setting., Competing Interests: Disclosure: The authors have no financial disclosures or conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Thrombosis is linked to neutrophil release of neutrophil extracellular traps (NETs). NETs are proposed as a mechanism of resistance to thrombolysis. This study intends to analyze the composition of thrombi retrieved after mechanical thrombectomy, estimate the age and organization of thrombi, and evaluate associations with the use of thrombolysis, antiplatelets, and heparin., Methods: This retrospective observational study involved 72 samples (44 from cerebral and 28 coronary arteries), which were stained with hematoxylin and eosin, anti-NE (neutrophil elastase) antibody, and anti-histone H2B (histone H2B) antibody, representing different components in NET formation, all detectable during the later stages of NETosis, for histochemical and digital quantification of NET content. The histological and morphological evaluations of the specimens were correlated, through univariate and mediation analyses, with clinical information and therapy administered before intervention., Results: The results demonstrated that the composition of cerebral and coronary thrombi differs, and there were significantly more lytic cerebral thrombi than coronary thrombi (66% versus 14%; P =0.005). There was a considerably higher expression of NETs in the cerebral thrombi as testified by the higher expression of H2B ( P =0.031). Thrombolysis was remarkably associated with higher NE positivity (average marginal effect, 6.461 [95% CI, 0.7901-12.13]; P =0.02555), regardless of the origin of thrombi. There was no notable association between the administration of antiaggregant therapy/heparin and H2B/NE amount when adjusted for the thrombus location. Importantly, the age of the thrombus was the only independent predictor of NET content without any mediation of the thrombolytic treatment ( P =0.014)., Conclusions: The age of the thrombus is the driving force for NET content, which correlates with impaired clinical outcomes. The therapy that is currently administered does not modify NET content. This study supports the need to investigate new pharmacological approaches added to thrombolysis to prevent NET formation or enhance their disruption, such as recombinant human DNase I (deoxyribonuclease I)., Competing Interests: Disclosures None.

Background: The present study aimed to evaluate the efficacy and safety of intravenous tirofiban versus alteplase before endovascular treatment (EVT) in acute ischemic stroke patients with intracranial large vessel occlusion., Methods: This was a post hoc analysis using data from 2 multicenter, randomized trials: the DEVT trial (Direct Endovascular Treatment for Large Vessel Occlusion Stroke) from May 2018 to May 2020 and the RESCUE BT trial (Intravenous Tirofiban Before Endovascular Thrombectomy for Acute Ischemic Stroke) from October 2018 to October 2021. Patients with acute intracranial large vessel occlusion within 4.5 hours from last known well were dichotomized into 2 groups: tirofiban plus EVT versus alteplase bridging with EVT. The primary outcome was functional independence (modified Rankin Scale score of 0-2) at 90 days. Safety outcomes included symptomatic intracranial hemorrhage and 3-month mortality. Multivariable logistic regression (adjusting for baseline systolic blood pressure, occlusion site, onset-to-puncture time, anesthesia, and first choice of EVT) and propensity score overlap weighting (balance in demographic covariates, stroke characteristics, and initial management between groups) were performed., Results: One-hundred and eighteen alteplase-treated patients in the DEVT trial and 98 tirofiban-treated patients in the RESCUE BT trial were included (median age, 70 years; 115 [53.2%] men). The rate of functional independence was 60.2% in the tirofiban group compared with 46.6% in the alteplase group (adjusted odds ratio, 1.25 [95% CI, 0.60-2.63]). Compared with alteplase, tirofiban was not associated with increased risk of symptomatic intracranial hemorrhage (6.8% versus 9.2%; P =0.51) and mortality (17.8% versus 19.4%; P =0.76). The propensity score overlap weighting analyses showed consistent outcomes., Conclusions: Among patients with intracranial large vessel occlusion within 4.5 hours of onset, tirofiban plus EVT was comparable to alteplase bridging with EVT regarding the efficacy and safety outcomes. These findings should be interpreted as preliminary and require confirmation in a randomized trial., Registration: URL: https://www.chictr.org.cn; Unique identifiers: ChiCTR-IOR-17013568 and ChiCTR-INR-17014167., Competing Interests: Disclosures Dr Nguyen reports being an associate editor for Stroke; compensation from Brainomix for the advisory board; compensation from Idorsia for the advisory board; pilot grant to her institution from the Society of Vascular and Interventional Neurology; compensation from Medtronic USA, Inc, for consultant services; and being a principal investigator for Route 92 Medical, Inc (no compensation). Dr Saver reports compensation from BrainQ for consultant services; stock options in Rapid Medical; stock options in Neuronics Medical; compensation from CSL Behring for consultant services; compensation from Biogen for consultant services; compensation from Roche for consultant services; compensation from Boehringer Ingelheim (prevention only) for consultant services; compensation from Abbott Laboratories for consultant services; compensation from Johnson & Johnson Health Care Systems, Inc, for consultant services; compensation from BrainsGate for consultant services; compensation from Aeromics for consultant services; stock options in MindRhythm; compensation from MIVI Neuroscience for data and safety monitoring services; and compensation from Medtronic USA, Inc, for consultant services. Dr Nogueira reports stock options in Corindus, Inc; compensation from Viz AI for consultant services; compensation from Synchron for data and safety monitoring services; compensation from Anaconda Biomed for consultant services; stock holdings in Quantanosis AI; stock options in Brainomix; compensation from NeuroVasc Technologies, Inc, for consultant services; compensation from Ceretrieve for consultant services; compensation from Imperative Care, Inc, for consultant services; compensation from Phenox, Inc, for consultant services; compensation from Brainomix for consultant services; compensation from Philips for consultant services; compensation from RapidPulse for consultant services; compensation from Cerenovus for consultant services; compensation from Hybernia for consultant services; stock options in Truvic; compensation from Brainomix for consultant services; compensation from Perfuze for consultant services; compensation from Genentech for consultant services; compensation from Stryker Corporation for consultant services; compensation from Prolong Pharmaceuticals for consultant services; compensation from Corindus Vascular Robotics for consultant services; stock options in Vesalio; compensation from Cerebrotech for consultant services; compensation from RapidPulse for consultant services; stock options in Reist/Q’Apel Medical; compensation from Astrocyte for consultant services; stock options in Perfuze; compensation from Genentech for consultant services; compensation from Phenox for consultant services; compensation from Stryker for consultant services; stock options in Viseon, Inc; compensation from Vesalio for consultant services; compensation from Medtronic USA, Inc, for consultant services; compensation from Anaconda for consultant services; compensation from Cerenovus for consultant services; stock options in Viz AI; stock options in Perfuze; compensation from Imperative Care for consultant services; compensation from Biogen, Inc, for consultant services; compensation from Medtronic USA, Inc, for consultant services; compensation from Vesalio for consultant services; stock options in Cerebrotech; grants from Cerenovus; compensation from Viz AI for consultant services; stock options in Ceretrieve; compensation from Biogen, Inc, for consultant services; stock options in Viz AI; stock holdings in Brain4Care; grants from Stryker; compensation from Ceretrieve for consultant services; stock holdings in Piraeus Medical; compensation from Shanghai Wallaby for consultant services; compensation from Perfuze for consultant services; compensation from Corindus, Inc, for consultant services; and compensation from Prolong Pharmaceuticals for consultant services. The other authors report no conflicts.