Citations

Antithrombotic therapy plays an important role in reducing stroke recurrence. For noncardioembolic stroke, multiple trials have demonstrated the efficacy of antiplatelet monotherapy for secondary stroke prevention. In select situations, such as short-term treatment in the acute period after a minor stroke or transient ischemic attack, dual-antiplatelet therapy has demonstrated superiority to monotherapy. Multiple trials have tested more aggressive strategies using long-term combination antiplatelet medications or full-dose anticoagulation with limited evidence of a reduction in ischemic events but a relatively consistent increased risk of bleeding. Emerging new agents targeting factor XI/XIa may uncouple necessary hemostasis from pathological thrombosis and offer promise for enhancing secondary prevention of stroke without increasing bleeding. The recently positive OCEANIC-STROKE trial (Oral Factor Eleven A Inhibitor Asundexian as Novel Antithrombotic) testing dual-pathway inhibition with the factor XIa inhibitor asundexian in combination with antiplatelet therapy represents a major advance in antithrombotic therapy for noncardioembolic stroke. This review summarizes the current state of the evidence for antithrombotic therapy in secondary stroke prevention after noncardioembolic stroke and discusses completed and ongoing trials of novel factor XI/XIa inhibitors for stroke prevention.

Abstract Introduction Atrial fibrillation (AF) is a major contributor to stroke risk, yet many cases remain undiagnosed due to its silent nature. Deep learning-based electrocardiogram (DL-ECG) analysis can streamline AF risk stratification, providing a more reliable and accessible method to stratify risk using only a standard resting ECG. However, this tool has been validated only on AF detected clinically or with short ECG event monitors. Purpose This study aimed to validate the predictive accuracy of a DL-ECG model for identifying AF in normal sinus rhythm (NSR) ECGs among patients undergoing continuous cardiac monitoring with implantable loop recorders (ILRs). Methods We conducted a historical cohort study across three major U.S. academic medical centers, enrolling patients with an ILR and no prior diagnosis or documented ECG evidence of AF. Pre-implantation 10-second, 12-lead ECGs in NSR were analyzed using the DL-ECG model. Performance was evaluated using the area under the receiver operating characteristic curve (AUC) and compared with the CHARGE-AF score. Kaplan-Meier survival analysis and Cox proportional hazards models assessed the association between DL-ECG risk categories and incident AF, defined as any episode lasting ≥6 minutes. Results We included 2,523 patients (mean age 66 ± 17 years, 52% male). AF was detected in 658 (26%) over a median follow-up of 19 months (IQR 8-37), Table 1. The DL-ECG model classified 1,634 patients (65%) as at low-risk and 889 (35%) as at high-risk. AF developed in 242 (14.8%) of the low-risk group and 416 (46.8%) of the high-risk group, yielding an AUC of 0.73 (95% CI 0.70-0.75), surpassing the CHARGE-AF AUC of 0.69 (95% CI 0.66-0.71). A combined DL-ECG and CHARGE-AF model yielded an AUC of 0.74 (95% CI 0.72-0.76), Figure 1 presents the AUC, Net Reclassification Index, and DeLong test comparisons among the three models. High-risk patients had a significantly higher incidence of AF, which remained significant after adjusting for CHARGE-AF variables, Figure 2. AF incidence increased as DL-ECG quartiles increased, with 61% of patients at the top quartile developing AF during follow-up, Figure 3. False negatives (patients initially classified as low-risk but in whom later AF was detected) had a longer median time to AF detection (127 days [IQR 28-425] vs. 101 days [IQR 20-318] for true positives, p = 0.01), and where found to have at least one positive ECG during follow-up in 36%, compared to 32% of true negatives, indicating eventual risk reclassification. Conclusions Among patients undergoing ILR monitoring, the DL-ECG model demonstrated superior predictive performance compared to CHARGE-AF, offering a promising and accessible alternative for early detection of silent AF. This approach could aid early AF detection, particularly in resource-limited settings where access to specialized rhythm monitoring services is limited.Table 1 and Figure 1 Figure 2 and 3

Objective Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiological diagnosis that can be associated with SLE. The clinical presentation, risk factors and outcomes of PRES in patients with SLE remain insufficiently described. Methods We conducted a multicentre cohort study at the Mayo Clinic and performed a systematic literature review (SLR) of patients with incident PRES and SLE. We described the clinical features, treatments and outcomes. Across both the cohort study and SLR, we assessed neurological sequelae, recurrence and survival. Within the cohort study, we examined PRES risk factors and discontinuation of antiseizure medications (ASMs). We used logistic regression to evaluate factors associated with neurological sequelae and Cox regression to assess predictors of recurrence. Kaplan-Meier methods estimated the rates of recurrence, survival and ASMs discontinuation. Results 550 cases (53 from the cohort study) were included, of whom 92% were female. Across both cohort and SLR, the most common symptom was seizure, occurring in 80%. PRES was the first manifestation of SLE in 13% of cases. In the adjusted analysis, older age was associated with neurological sequelae (OR 1.63 per 10-year increase; 95% CI 1.12 to 2.39). After 5 years of follow-up, 11.5% (95% CI 2.3 to 19.9%) of patients had a recurrent PRES episode. 30-day and 180-day survival following PRES was observed in 96.3% (95% CI 93.5 to 99.1%) and 93.7% (95% CI 89.8 to 97.7%) patients, respectively. In the Mayo Clinic cohort, 81% of PRES cases were attributed to hypertension in the context of lupus nephritis (LN), and by the fifth year of follow-up, 78.1% (95% CI 58.7 to 88.4%) of patients had discontinued ASMs. Conclusions In this cohort, most of the incident PRES episodes were preceded by hypertension and occurred in patients with LN. Although short-term and long-term prognoses are favourable, older patients more frequently experienced neurological sequelae.

Oral nimodipine is the only drug approved for aneurysmal subarachnoid hemorrhage (aSAH). However, bioavailability is poor and peak plasma concentrations fluctuate widely, leading to dose‐limiting hypotension. Administration is problematic in patients who cannot swallow. An enteral liquid formulation exists but causes severe diarrhea. GTX‐104 is an intravenous (IV) nimodipine formulation that has 100% bioavailability and is not affected by swallowing, gastrointestinal absorption and first pass effects. When administered in pharmacokinetically‐equivalent doses to oral nimodipine in healthy humans, GTX‐104 has more consistent plasma concentrations and causes less hypotension than oral nimodipine. To conduct a randomized, open label, blinded endpoint study to determine the safety and tolerability of GTX‐104 compared with oral nimodipine in patients with aSAH We conducted a multicenter, prospective, randomized, open‐label safety and tolerability study of GTX‐104 compared to oral nimodipine in aSAH. Inclusion/exclusion criteria matched prescribing information for oral nimodipine and included adults with aSAH of all Hunt/Hess grades. Subjects were randomized 1:1 to GTX‐104 or oral nimodipine. The primary endpoint was the proportion of subjects with clinically significant hypotension (hypotension requiring treatment, with a reasonable likelihood of being due to study drug, as determined by an independent, blinded committee). Secondary endpoints included all episodes of hypotension, adverse events, EQ‐5D‐3L and modified Rankin scale within 90 days of aSAH. 102 subjects were randomized at 24 sites in the USA. Demographics reflected those of aSAH. There was a 20% relative reduction in clinically significant hypotension with GTX‐104 compared to oral nimodipine (28% versus 35%). 54% of GTX‐104 subjects got >95% of the prescribed dose compared to 8% on oral nimodipine. Favorable outcome (90‐day mRS 0‐2) was more common in the GTX‐104 group compared with oral nimodipine (62% versus 48%). Fewer patients on GTX‐104 (36% versus 48% oral nimodipine) had serious adverse events. There were no safety issues with GTX‐104. GTX‐104, an IV formulation of nimodipine that can be administered through central or peripheral veins, is safer and potentially more efficacious than oral nimodipine.

ABSTRACT Background Intracranial and extracranial hemorrhages are significant causes of morbidity and mortality. Emergency medicine pharmacists (EMPs) can play a crucial role in anticoagulation reversal by identifying patients on anticoagulation, selecting the optimal anticoagulation reversal agent, and ensuring adequate dosing and prompt administration. The goal of this systematic review and meta‐analysis was to determine the impact EMPs have on time to anticoagulation reversal and patient outcomes in anticoagulation‐associated hemorrhages. Methods A medical librarian performed a literature search in EBSCO CINAHL, Ovid Cochrane Central Register of Controlled Trials, Ovid Embase, Ovid Medline, Scopus, and Web of Science Core Collection from inception to January 2025 for all types of oral anticoagulants and for life‐threatening bleeding that required emergent reversal. Newcastle‐Ottawa was used to assess the risk of bias, and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to assess the level of certainty of the evidence. Random effects models estimating mean differences and 95% confidence intervals are reported. Results There were 2445 titles and abstracts screened, with 44 undergoing full‐text evaluation. Six observational studies including 219 patients who received an anticoagulation reversal agent with the presence of an EMP and 198 patients who received a reversal agent without an EMP were included. Time from emergency department (ED) presentation to anticoagulation reversal agent administration (75.60 min, 95% confidence interval [CI]: −101.7 to −49.5) and time from medication order to administration were faster with an EMP (−18.7 min, 95% CI: −23.5 to −14.0). There was no difference in short‐term mortality. The included studies had a high risk of bias and were deemed very low quality of evidence. Conclusion EMP involvement in patient care during anticoagulation reversal of acute hemorrhages improved time to anticoagulation reversal agent administration. Larger scale, higher‐quality studies are necessary to assess the value of EMPs in improving patient‐centered outcomes.