Opeolu Adeoye

Background: Several observational studies have supported the use of conscious sedation (CS) for endovascular thrombectomy in patients with acute ischemic stroke and associated general anesthesia (GA) with poor functional outcomes. Recently, few randomized controlled trials have shown no difference in the functional outcomes between GA and CS. The aim of this paper is to compare the outcomes of GA versus CS in patients with acute ischemic stroke undergoing mechanical thrombectomy in the MOST (Multi‐arm Optimization of Stroke Thrombolysis) trial. Methods: Patients who underwent mechanical thrombectomy for acute ischemic stroke under GA or CS in the MOST trial were included. The primary outcome of interest was the utility weighted modified Rankin Scale (mRS) score at 90 days after stroke. The secondary outcomes were mRS score ≤1, ≤2 at 90 days, 90‐day mRS score, thrombolysis in cerebral infarction 2B or better, 24‐hour National Institutes of Health Stroke Scale score, 24‐hour change in National Institutes of Health Stroke Scale score, and 90‐day mortality. Results: A total of 219 patients underwent mechanical thrombectomy with 101 patients receiving GA and 118 patients receiving CS. Our analysis showed that GA was associated with a lower average utility weighted mRS score at 90 days compared with CS ( P ≤0.02). Similarly, GA was associated with higher odds of worse outcomes on 90‐day mRS 0 to 2 ( P P P P <0.001). A sensitivity analysis of patients with anterior stroke alone also favored better neurologic outcomes in the CS group compared with the GA group. Conclusions: In patients undergoing endovascular thrombectomy in the MOST trial, GA was associated with poorer functional outcomes compared with CS.

BACKGROUND: Despite a rising public health burden, there have been few population-based studies of chronic subdural hematomas (cSDH) in the United States. We provide the first estimates of cSDH incidence and mortality in a large, representative U.S. population. METHODS: In a representative 5-county region of Southern Ohio and Northern Kentucky, all adults with cSDH in 2019 and 2020 were identified and adjudicated by study physicians. Incidence rates were estimated and standardized to the US population based on age, sex, and race; 30-day and 1-year mortality rates were also estimated. The cause of death was determined using the National Death Index. RESULTS: A total of 353 patients with cSDH were identified. The median age was 76 (IQR, 65–85), 231 were men (65.4%), and 78 were Black (22.1%). Clinical frailty was prevalent among patients (the median retrospective score on the clinical frailty scale was 4), and only 128 (36.3%) were functionally unimpaired at baseline. The regional incidence rate was 16.3 cases/100 000 persons/y (95% CI, 13.9–19.0). Incidence was age- and sex-dependent, with men 85 and older having an incidence rate of 354.8 cases/100 000 persons/y (95% CI, 242.7–500.9). When adjusted to national demographics, the estimated overall US incidence rate was 17.3 cases/100 000 persons/y (95% CI, 14.7–19.9). The 30-day mortality rate after cSDH was 9.4% (95% CI, 6.5–12.9), and the 1-year mortality rate was 32.9% (28.0–38.0). Early mortality (≤30 days) was often partly or fully attributed to the cSDH (48.4% versus 16.1%; P =0.0004), whereas the most common causes of later mortality were neurodegenerative and cardiovascular diseases (27.2% and 28.4%, respectively). CONCLUSIONS: Our contemporary population-level data show that cSDH is common in the US and primarily afflicts patients with a high degree of functional impairment and frailty. While short-term mortality is low, longer-term mortality is high and often related to comorbid illnesses.

The STAIR (Stroke Treatment Academic Industry Roundtable) sponsored a workshop during the STAIR XIII conference in Washington, DC on March 27 to 28, 2025, to develop consensus recommendations, particularly regarding research priorities and design elements for trials of reperfusion therapies. This forum brought together stroke neurologists, neuroradiologists, neuroimaging research scientists, members of the National Institute of Neurological Disorders and Stroke, and industry representatives to discuss future developments in reperfusion therapies. The reperfusion trials session summarized and compared recent acute stroke trials. The workshop developed consensus recommendations for research priorities and trial design challenges. Given that the majority of patients eligible for reperfusion therapies present initially to primary stroke centers, developing research networks that allow trials to be conducted in the transfer setting and overcome the logistical challenges in such centers was identified as a key priority. A particular focus was the definition and investigation of microvascular reperfusion and the no-reflow phenomenon. Potential trial paradigms to advance the field were discussed. Recent acute stroke clinical trials have extended the scope of intravenous thrombolytics and endovascular thrombectomy. Recruitment for future trials at both primary and comprehensive stroke centers, in addition to standard of care, poses challenges, particularly for novel thrombolytics. Recommendations for enhancing stroke imaging research and the definition of macrovascular versus microvascular reperfusion are provided.

Background: Intravenous thrombolysis for acute ischemic stroke (AIS) is a proven effective treatment. Whether thrombolysis in patients with AIS with recent direct oral anticoagulant (DOAC) use is safe and efficacious is not well established. We aimed to compare outcomes of patients with AIS and recent DOAC use who received thrombolysis to those otherwise eligible but excluded due to recent DOAC use. Methods: This study included patients for the GWTG (Get With The Guidelines) registry with a diagnosis of AIS within 4.5 hours from last known normal, on a DOAC, and either (1) received intravenous thrombolysis, or (2) were excluded from thrombolysis with coagulopathy being the only reason for exclusion. We used univariate and adjusted binary logistic regression models with clustering by site to compare the 2 groups’ functional status (ambulation on discharge and discharge disposition) and reported rates of safety outcomes in the thrombolysis group. Results: The study sample included 48 907 patients with AIS using a DOAC; 4702 received thrombolysis and 44 205 did not. In adjusted logistic regression models, patients with recent DOAC use receiving thrombolysis had increased odds of independent ambulation at discharge (odds ratio [OR], 1.35[ 95% CI, 1.21–1.50]) and home discharge (OR, 1.33 [95% CI, 1.22–1.46]). The rate of symptomatic intracranial hemorrhage with intravenous thrombolysis in patients with recent DOAC use was 3.5% (95% CI, 3.0%–4.1%). Conclusions: In this study, intravenous thrombolysis was associated with improved functional outcomes in patients with recent DOAC use and appeared safe. Given the study limitations, findings require validation by prospective trials.

The Stroke Treatment Academic Industry Roundtable convened a workshop regarding artificial intelligence (AI) and innovative clinical trial designs during the Stroke Treatment Academic Industry Roundtable XIII meeting on March 28, 2025. This forum brought together stroke physicians and researchers, and industry representatives to discuss the current use and future opportunities for AI and novel trial designs in acute stroke trials. AI already plays a substantial role in the treatment of acute stroke with regards to imaging but is poised to have a much larger impact in clinical care and research trials over the coming years. The quality and understanding of the data are used to train the AI, the human element needed to ensure training is successful, and the clinician and trialist at the bedside, the humans “in the loop,” will be necessary to maximize AI’s effectiveness in clinical practice and trials. Platform trials address multiple scientific questions in an area of medicine simultaneously within the same trial structure by sharing controls across multiple interventions. While platform trials increase efficiency and potentially decrease the time needed to answer important clinical scientific questions, they also can introduce complexity to standard workflows. Future acute ischemic stroke clinical trials should incorporate elements of pragmatic and patient-centered trial design when possible. Pragmatic trials aim to assess the effectiveness of treatments when they are implemented into routine clinical care rather than under idealized conditions. AI models and platform, pragmatic, and patient-centered trial designs are new tools to answer important clinical questions, but understanding how they work, their best uses, and their limitations is critical for accelerating successful new treatments for stroke.

IV thrombolysis only (IVT-O) is the primary reperfusion therapy for most stroke patients. At least 50% of IVT-O patients remain disabled. We assessed 2 therapies added to IVT-O aimed at increasing clot lysis or preventing arterial reocclusion. This 3-arm, adaptive, single-blinded, randomized controlled phase III clinical trial was conducted at 57 US sites. Patients with acute ischemic stroke (AIS) within 3 hours of onset receiving IV tissue plasminogen activator or tenecteplase were randomized to argatroban (100 μg/kg bolus and 12-hour infusion at 3 μg/kg/min), eptifibatide (135 μg/kg bolus and 2-hour infusion at 0.75 μg/kg/min), or placebo (bolus and 12-hour infusion). The primary end point was utility-weighted 90-day modified Rankin Scale score (uwmRS score; worst = 0, best = 10). This prespecified secondary analysis was conducted on the intent-to-treat population in the IVT-O cohort using a Bayesian normal dynamic linear model. Of 514 patients enrolled into Multi-arm Optimization of Stroke Thrombolysis (MOST) before the study was stopped for futility, 260 were in the IVT-O cohort (118 treated with placebo, 114 with eptifibatide, and 28 with argatroban; mean age 66 years, 46.9% female). Baseline variables were similar across groups (median NIH Stroke Scale score 8, mean time from symptom onset to IVT 105 minutes, mean time from IVT bolus to study drug start 62 minutes). A clot was visible in 30.8% of patients. There was only a 1% or 2.5% chance that argatroban or eptifibatide, respectively, was superior to placebo for the primary outcome (mean uwmRS scores [SD] of 5.5 [3.6], 6.6 [3.2], and 7.4 [2.6] for argatroban, eptifibatide, and placebo, respectively). No secondary outcomes favored either treatment group. The risk difference for symptomatic hemorrhage between the argatroban and eptifibatide arms vs placebo was -0.8% (p = 0.82) and 1.8% (p = 0.36). Mortality was 3.4% with placebo, 14.3% for argatroban (p = 0.03), and 11.4% for eptifibatide (p = 0.02). There was no benefit in any subgroup. Outcomes in patients treated with IVT-O were not improved by adding either argatroban or eptifibatide. Increased bleeding was not observed, but mortality was higher in both investigational arms. Limitations included small sample size in the argatroban subgroup. This study was registered on ClinicalTrials.gov (registration number: NCT03735979) on November 8, 2018. The first patient was enrolled on October 15, 2019. This study provides Class II evidence that in patients with AIS treated with IVT within 3 hours of onset, argatroban or eptifibatide does not improve outcomes vs thrombolysis alone but does increase mortality.

Thrombolytics and mechanical thrombectomy are standard of care therapies for the treatment of acute ischemic stroke. Optimizing reperfusion beyond these 2 interventions is a critical next step to improving patient outcomes. The utility of antithrombotic medications is well-established for secondary stroke prevention, but their role as adjunctive therapies to achieve or optimize reperfusion in the acute setting remains investigational. This article discusses the rationale for the use of adjunctive antithrombotic medications in combination with reperfusion therapies and reviews key trials exploring their use. We will use the term adjunctive to refer to any antithrombotic intervention that is added acutely to the standard of care of thrombolysis or thrombectomy to improve patient outcomes. A brief discussion on the future of adjunctive therapies for current reperfusion strategies and the best use of antithrombotic medications in the hospital setting are additionally presented.

BACKGROUND: Obtaining timely informed consent is a key barrier in acute ischemic stroke clinical trial recruitment. Electronic consent (eConsent) allows electronic delivery and documentation of the informed consent process, which may optimize recruitment. eConsent in acute ischemic stroke clinical trials, however, is limited and understudied. We conducted a post hoc analysis of eConsent adoption in MOST (Multi-Arm Optimization of Stroke Thrombolysis Trial), a phase III acute ischemic stroke clinical trial, and studied the impact on recruitment. METHODS: From October 10, 2019, to July 5, 2023, MOST enrolled 514 participants at 57 sites in the United States. Study databases were reviewed to determine informed consent modality for each participant: paper—in person, paper—remote, eConsent—in person, and eConsent—remote. Study sites could use paper consent or eConsent for each enrollment. eConsent adoption trends and participant demographic diversity were reported using descriptive statistics. We utilized χ ² and Kruskal-Wallis tests to compare individual site enrollment, remote consent utilization, baseline neuroimaging-to-randomization times, data clarification requests, and reportable consent-related unanticipated events. RESULTS: eConsent was utilized for 173 (33.7%) of 514 participants. Of 57 sites, 32 (56.1%) utilized eConsent at least once: those sites had higher median enrollment over the course of the entire trial than non-eConsent sites (7.5 [interquartile range, 5–17] versus 3 [interquartile range, 2–4]; P P <0.001). Participant demographic diversity and baseline neuroimaging-to-randomization times were similar between eConsent—in person and paper—in person (median, 58.5 [interquartile range, 46.5–72.5] versus 55 [interquartile range, 39–70] minutes). Consent documentation adherence was superior with eConsent—in person compared with paper—in person including decreased data clarification requests (44 versus 81 per 100 participants) and reportable unanticipated events (6 versus 25 per 100 participants). CONCLUSIONS: eConsent in MOST was associated with higher individual site enrollment, higher remote consent rates, and improved consent documentation adherence over paper consent. Our study outlines the potential advantages of eConsent adoption in future acute ischemic stroke clinical trials and stroke research networks.

BACKGROUND: The modified Rankin Scale (mRS) is a key measure of functional outcomes in stroke trials. To minimize variability, structured tools like the Rankin Focused Assessment and central adjudication are recommended. This study compares local versus centrally adjudicated mRS scores in the MOST trial (Multi-Arm Optimization of Stroke Thrombolysis). METHODS: MOST was a phase 3, single-blind, randomized trial evaluating argatroban, eptifibatide, or placebo in addition to intravenous thrombolysis. The primary outcome, 90-day mRS score, was gathered through in-person video recordings by blinded local personnel. Recordings were sent to central adjudicators for final scoring. As in-person visits became limited due to SARS-CoV-2, remote interviews were allowed. We hypothesized that local mRS scores would be moderately associated with central scores. Fleiss-Cohen quadratic weighted κ statistics were used to determine the strength of agreement. RESULTS: Out of 514 participants, 378 had recorded visits available (121 in-person video, 157 remote video, 100 remote audio). Local assessors were blinded 96.8% of the time and 85.4% of visits used the Rankin Focused Assessment. Overall agreement between local and central mRS scores was excellent (weighted κ, 0.87 [95% CI, 0.83–0.90]). A nonsignificant decrease in strength of agreement was noted for those with a nonzero baseline mRS (mRS score=0, 0.87 [95% CI, 0.84–0.91] versus mRS score >0, 0.80 [95% CI, 0.68–0.91]). Trial conclusions were unchanged when utilizing the local mRS versus central adjudication. CONCLUSIONS: Local mRS scores demonstrated strong agreement with central scores across all assessment modes. With blinded end point assessments, central mRS adjudication in acute stroke trials may not be necessary. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03735979.