Short-term dual antiplatelet treatment (DAPT) is superior to single antiplatelet treatment (SAPT) for secondary prevention in non-cardioembolic minor ischemic stroke and high-risk transient ischemic attack (TIA). As the real-world use of DAPT is broader than in trials, it is important to clarify its benefit/risk profile in a diverse population.

Post hoc analysis of prospectively collected data from the READAPT cohort and three prospective stroke registries including patients with mild-to-moderate (National Institute of Health Stroke Scale (NIHSS) score 0-10) ischemic stroke receiving early DAPT or SAPT. The primary effectiveness outcome was 90-day return to pre-stroke neurological functioning using modified Rankin Scale (mRS) score. Secondary effectiveness outcomes were 90-day mRS shift, new ischemic stroke/TIA, vascular and all-cause death, 24 h early neurological improvement or deterioration. The safety outcome was 90-day intracranial hemorrhage.

We matched 1008 patients treated with DAPT and 1008 treated with SAPT. Compared to SAPT, patients treated with DAPT showed higher likelihood of 90-day primary effectiveness outcome (87.5% vs. 84.4%, risk difference 3.1% (95% confidence interval (CI): 0.1%-6.1%); p = 0.047, risk ratio 1.03 (95% CI: 1.01-1.07); p = 0.043) and higher rate of 24-h early neurological improvement (25.3% vs. 15.4%, risk difference 9.9% (95% CI: 6.4%-13.4%); p < 0.001, risk ratio 1.65 (95% CI: 1.37-1.97); p < 0.001). No differences were observed for other study outcomes. Subgroup analysis confirmed benefit of DAPT over SAPT for primary effectiveness outcome in patients with moderate stroke, those treated with intravenous thrombolysis, and those who received antiplatelet loading dose.

Our findings suggest that DAPT use might be safe and more effective than SAPT even in the real world and in patients who do not strictly fulfill the criteria of landmark large clinical trials.

Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin is recommended for secondary prevention in patients with a minor stroke or transient ischemic attack. However, the effectiveness of DAPT can be significantly influenced by genetic variations. This study aimed to estimate the impact of multiple single-nucleotide polymorphisms across various genes on DAPT efficacy using polygenic risk score (PRS).

In this post hoc analysis, we included 2905 patients from the CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events), which enrolled a total of 5170 patients in China between October 2009 and July 2012. The primary outcome was new stroke within 90 days. Sixteen single-nucleotide polymorphisms across 7 genes involved in clopidogrel metabolism were selected for PRS development. PRS were calculated by summing single-nucleotide polymorphisms from each individual. The Cox proportional-hazards regression model was utilized to estimate the hazard ratio (HR) and 95% CIs of PRS. The predictive value of PRS was estimated by C statistic and compared with a previously validated model.

The elevated PRSs were associated with an increased risk of new stroke within 90 days (Ptrend=0.01). The efficacy of DAPT versus aspirin alone in preventing 1-year composite vascular events was significantly different between patients with low (adjusted HR, 0.47 [95% CI, 0.31-0.71]) and high PRSs (adjusted HR, 0.84 [95% CI, 0.60-1.18]; Pinteraction=0.03). In patients receiving DAPT, higher PRSs were associated with increased risk of new stroke and composite vascular events at 90 days (adjusted HR per SD increase was 1.51 [95% CI, 1.15-1.99]) and at 1 year (adjusted HR per SD increase was 1.34 [95% CI, 1.08-1.67]). The C statistic for predicting 90-day new stroke using the PRS developed in this study was 0.57 (95% CI, 0.52-0.62), compared with 0.52 (95% CI, 0.48-0.55) for the ABCD-GENE score.

Using PRS integrating multiple genes may enhance the precision of secondary prevention strategies for patients with minor stroke or transient ischemic attack in the short and long term.

URL: https://www.clinicaltrials.gov; Unique identifier: NCT00979589.

According to the literature, about one third of patients with brain ischemic symptoms lasting <24 h, which are classified as Transient ischemic attacks (TIAs) according to the traditional "time-based" definition, show the presence of acute ischemic lesions at neuroimaging. Recent evidence has shown that the presence of acute ischemic lesions at neuroimaging may impact on the outcome of patients with transient ischemic symptoms treated with dual antiplatelet treatment (DAPT). This uncertainty is even more compelling in recent years as short-term DAPT has become the standard treatment for any non-cardioembolic TIA or minor ischemic stroke.

This is a pre-specified subgroup analysis from a prospective multicenter real-world study (READAPT). The analysis included patients with time-based TIA-that is, those with ischemic symptoms lasting <24 h-who started DAPT. In the whole population, we assessed the presence of acute brain ischemic lesions at neuroimaging and their association with the ABCD2 score. To assess the impact of acute brain ischemic lesions on 90-day prognosis, we performed a propensity score matching of patients with and without those lesions. We adopted a primary effectiveness outcome which was a composite of new stroke/TIA events and death due to vascular causes at 90 days.

We included 517 patients-324 (62.7%) male-with a median (interquartile range-IQR) age of 74 (IQR = 65-81) years; 144 patients (27.9%) had acute brain ischemic lesions at neuroimaging. The proportion of patients with brain ischemic lesions did not vary according to the ABCD2 score. At follow-up, 4 patients with brain ischemic lesions (2.8%) and 21 patients without lesions (5.6%) reported the primary effectiveness outcome, which was similar between the groups before (p = 0.178) and after matching (p = 0.518).

In our population, patients with transient ischemic symptoms and acute ischemic lesions at brain magnetic resonance imaging (MRI) had a risk of recurrent ischemic events similar to those without lesions. The risk of recurrent ischemic events was low in both groups.

Intravenous thrombolysis for acute minor ischaemic strokes did not provide any benefit in the recent TEMPO-2 trial. In general, single antiplatelet agents are used to improve the outcomes after thrombolysis. This systematic review was done to assess the impact of dual antiplatelet therapy (DAPT) after thrombolysis in patients with minor stroke.

A literature search was performed on PubMed, The Cochrane Library and Science Direct for articles between 2016 and 2024. All studies included patients with minor stroke, aged ≥18 years, National Institutes of Health Stroke Scale score of ≤5 (or 3) and those who received thrombolysis prior to DAPT. The primary endpoint was modified Rankin Scale (mRS) score of 0-1 at 90 days. The quality of the studies was assessed using the Newcastle Ottawa Scale. Risk ratios (RRs) were calculated, and subgroup analysis was done.

Only 4 out of 4364 studies originally retrieved met the inclusion criteria and were included. The analysis showed that the mRS score improvement at 90 days was almost similar in both DAPT and single antiplatelet therapy (SAPT) groups (RR 1.09; 95% CI (0.98, 1.21), p=0.11). Risk of symptomatic intracranial haemorrhage (SICH) (RR 0.65; 95% CI (0.11, 3.97), p=0.64) and stroke recurrence (RR 0.88; 95% CI (0.44, 1.78), p=0.64) was reduced with DAPT compared with SAPT without any major significance.

While these findings could not establish the superiority of DAPT over SAPT, DAPT showed slightly better results in functional outcomes, reducing the risk of stroke recurrence and SICH after thrombolysis in patients with minor stroke.

CRD42024593717.

This study evaluated the safety and efficacy of self-retaining barbed double-layer sutures (SRBDS) used for wound sutures in stage T1 renal cancer undergoing peritoneal robot-assisted laparoscopic partial renal resection.

A total of 50 patients undergoing robot-assisted laparoscopic partial nephrectomy (RAPN) for localized renal tumors (< 7 cm) in Zhejiang Provincial People's Hospital from January 2021 to January 2022 were selected. The experimental-group and the control-group randomly included 25 patients, respectively. SRBDS was intended to be used for kidney wound repair in the experimental group, and single-needle Vicryl was applied in the control group.

Patients in both the experimental group and the control group completed RAPN without conversion to open surgery. The operative time (80.20 ± 18.39 min) and warm ischemia time (11.76 ± 1.16 min) of the experimental group were both reduced compared to the control group (86.00 ± 15.94 min, 14.56 ± 1.04 min). The increased changes in blood creativity at one week and three months postoperatively in the experimental group were significantly lower than those in the control group, and the decreased changes in GFR level at three months postoperatively in the experimental group were significantly lower than that in the control group (5.21 ± 2.14 vs 7.81 ± 2.28, P < 0.05).

For localized T1 renal carcinoma, SRBDS is a safe and efficient endoscopic suture technique, which may be considered as an alternative to other suturing techniques, tissue sealants, and glues for RAPN in the future.

This study aims to evaluate temporal trends of advanced treatments and related clinical outcomes of ischemic stroke through a decade-long trend analysis, using data from a comprehensive, national, multicenter registry. We also seek to identify areas in need of improvement.

This analysis involved patients with ischemic stroke or transient ischemic attack registered prospectively in the CRCS-K-NIH (Clinical Research Center for Stroke in Korea-National Institute of Health) registry between 2011 and 2020. We examined temporal trends in risk factors, pathogenetic subtypes, acute management strategies, and outcomes for up to 1 year following a stroke. Generalized linear mixed models were used to account for center clustering. The average age of 77 662 patients increased 2.2 years in men and 2.4 years in women over the 10-year follow-up. Notably, in-hospital neurological deterioration, 3-month and 1-year mortality rate, and cumulative incidence of recurrent stroke within 1-year decreased over time after adjustments for age, sex, and initial stroke severity (P<0.01). However, functional outcomes at 3 months and 1 year remained unchanged. Endovascular thrombectomy increased from 5.4% in 2011 to 10.6% in 2020. Use of anticoagulants for atrial fibrillation, dual antiplatelet therapy, statins, and stroke unit care also increased. Contrarily, the rate of intravenous thrombolysis showed a slight decline.

This study points to a reduction in death and risk of recurrent stroke over the past decade, paralleling enhancement in acute and preventive stroke management. Nevertheless, the decline in the use of intravenous thrombolysis and the lack of improvement in functional outcomes following stroke are concerning trends that warrant thorough investigation.

Antithrombotic therapy is the cornerstone of stroke prevention, but standard of care therapies are underutilized and use is limited by bleeding rates, drug interactions, and renal elimination. Factor XI/XIa (FXI/XIa) inhibitors are a novel anticoagulation class that purportedly target thrombosis more than hemostasis, thereby raising the hope of reducing bleeding consequences while maintaining efficacy.

This review covers the mechanistic rationale for FXI/XIa inhibitors, describes the various molecule sub-classes, addresses barriers to current anticoagulation use, and reviews clinical trial data to date for this novel class of anticoagulants.

FXI/XIa inhibitors offer several advantages over DOACs in stroke prevention such as reduced bleeding, fewer drug interactions, and less renal elimination. However, clinical trials must demonstrate non-inferior efficacy and improved safety compared to DOACs. Additional barriers to use will include cost, inadequacy of antidotes, and overall anticoagulant underutilization. The potential for a small molecule or monoclonal antibody to reach the clinic is very high.

Transient Ischemic Attacks (TIAs) are a common reason for Emergency Department (ED) visits and represent a significant public health issue. Patients experiencing TIAs often face significant delays in undergoing various tests due to ED overcrowding and limited availability of neurologists. Emergency physicians (EPs) and neurologists have identified several criteria for allowing outpatient management. We conducted this study to assess the safety of this approach.

A reappointment pathway was established to oversee the management of TIAs following an ED visit. The primary objective was to evaluate the safety of this pathway by monitoring any events occurring between discharge from the ED and the neurology reappointment. We conducted a retrospective descriptive single-center study of patients who benefited from this pathway between September 2021 and September 2023. In the case of an event, we assessed sequalae using NIHSS and Modified Rankin Scale.

186 patients were included, with a mean age of 64 years. 53.7 % were women. The median ABCD2 score was 3. The median time spent in the ED was 444 min. Eight patients experienced an event. The risk of post-TIA event was 2.7 % at 30 days, and 3.2 % at 90 days. None of the patients had sequala at the end of the follow-up. 12.9 % of MRI scans revealed recent established strokes.

Our study demonstrates the safety of a systematic reappointment pathway for patients presenting with TIAs in the ED. Future research should validate our results with larger cohorts and explore strategies to optimize outpatient management of patients.

This article discusses the evolving definitions of transient ischemic attack and minor strokes, highlighting the shared risk factors and the similarities in approach and early management. It emphasizes the importance of early identification and basic workup for these patients, as well as the most effective early antithrombotic therapies to date. The article also emphasizes the significance of controlling risk factors and concludes with a discussion of treatment strategies based on specific stroke etiologies.

Currently, there is not sufficient data regarding the prevalence of resistance or inadequate platelet function inhibition with the use of antiplatelet therapy in patients with noncardioembolic stroke. This study was designed to evaluate the prevalence of antiplatelet inactivity to aspirin and clopidogrel in the setting of chronic use and presentation with primary or recurrent stroke.

Patients who were taking aspirin, clopidogrel, or both at the time of presentation for stroke were selected in this study. Those with confirmed stroke on MRI or clinically determined TIA and age > 18 years were included. A standard laboratory test, VerifyNow aspirin or P2Y12 assay, was utilized to assess the responsiveness to the platelet inhibitors. A total of 158 patients were identified, 52 presenting with primary stroke and 106 with recurrent stroke. Data were analyzed using chi-squared or Fisher's exact as well as t-test analysis.

Of the primary stroke population, 4% of patients demonstrated resistance to aspirin and 30% to clopidogrel. Of the patients presenting with recurrent stroke, 13% demonstrated resistance to aspirin and 38% to clopidogrel. The data also suggest increased resistance to aspirin and clopidogrel in Caucasians compared to minorities, with 11% versus 8% in regard to aspirin and 33% versus 17% to clopidogrel. Additionally, this study demonstrated 17% resistance to aspirin in males compared to 4% in females and 13% in males compared to 36% in females, respectively, regarding resistance to clopidogrel. No difference in inactivity to either aspirin or clopidogrel was detected between patients with stroke mechanisms of small or large vessel disease.

The present result demonstrated that a sizeable portion of the population has inefficacious activity in the setting of specific antiplatelet agents. Additionally, sex and ethnicity differences in responsiveness to aspirin or clopidogrel have been noted. Determining a patient's response to medications could provide opportunities to individualize treatment and better prevent future strokes. Further studies of a larger scale are indeed needed to apply this information to pursue individualized treatment.

Stroke recurrence remains a critical challenge in clinical neurology, necessitating the identification of reliable predictive markers for better management and treatment strategies. This study investigates the interaction between lipoprotein-associated phospholipase A2 (Lp-PLA2) and platelets as a potential predictor for stroke recurrence, aiming to refine risk assessment and therapeutic approaches. In a retrospective cohort of 580 ischemic stroke patients, we analyzed clinical data with a focus on Lp-PLA2 and platelet levels. By using multivariable logistic regression, we identified independent predictors of stroke recurrence. These predictors were then used to develop a comprehensive nomogram. The study established diabetes mellitus, hypertension, low-density lipoprotein (LDL), Lp-PLA2 levels, and platelet counts as independent predictors of stroke recurrence. Crucially, the interaction parameter Lp-PLA2 * platelet (multiplication of Lp-PLA2 and platelet count) exhibited superior predictive power over each factor considered separately. Our nomogram incorporated diabetes mellitus, cerebral infarction causes, hypertension, LDL, and the Lp-PLA2 * platelet count interaction and demonstrated enhanced accuracy in predicting stroke recurrence compared to traditional risk models. The interaction between Lp-PLA2 and platelets emerged as a significant predictor for stroke recurrence when integrated with traditional risk factors. The developed nomogram offers a novel and practical tool in molecular neurobiology for assessing individual risks, facilitating personalized treatment strategies. This approach underscores the importance of multifactorial assessment in stroke management and opens avenues for targeted interventions to mitigate recurrence risks.

Novel strategies are needed for the treatment of acute ischemic stroke when revascularization therapies are not clinically appropriate or are unsuccessful. rKLK1 (recombinant human tissue kallikrein-1), a bradykinin-producing enzyme, offers a promising potential solution. In animal studies of acute stroke, there is a marked 36-fold increase in bradykinin B2 receptor on brain endothelial cells of the ischemic region. Due to this environment, rKLK1-generated bradykinin will exert a potent local vasodilation and increase brain perfusion via 3 synergistic signaling pathways downstream to the B2 receptor. Because of its preferential effect on ischemic tissue, systemic adverse effects such as hypotension are avoided with proper dosing. In addition, with initial vasodilation through recruitment of preexisting collaterals, rKLK1 promotes long-term benefit of brain perfusion by promoting new collateral formation. With an extended course of therapy for weeks after acute ischemic stroke, these multifaceted effects may also reduce the risk of stroke recurrence. A prior phase II trial demonstrated a favorable impact on clinical outcomes and recurrent strokes, particularly among patients who were not eligible for mechanical thrombectomy. A phase II/III trial has launched in this population, though opportunities for combination revascularization therapies deserve further investigation.

Different stroke etiologies are associated with varied incidences of early neurological deterioration (END) in patients with acute ischemic stroke (AIS). The Tirofiban for the Prevention of Neurological Deterioration in Acute Ischemic Stroke (TREND) trial demonstrated the efficacy of tirofiban in preventing END in patients with AIS. Herein, we conducted a pre-specified subgroup analysis of this trial data to investigate whether stroke etiologies influenced the effects of tirofiban.

We performed a pre-specified subgroup analysis of the TREND trial, including 413 patients with AIS classified into large-artery atherosclerosis (n = 114), small-vessel occlusion (n = 124), and undetermined etiology (n = 175). The primary outcome was the incidence of END4 (defined as an increase in the National Institutes of Health Stroke Scale (NIHSS) score by ⩾ 4 points) within 72 h. Other outcomes included END2 (increase in NIHSS score by ⩾ 2 points), early improvement, functional outcomes at 90 days, and safety profiles.

Tirofiban significantly reduced the risk of END4 in patients with large-artery atherosclerosis (4.1% vs. 21.5%; adjusted odds ratio (OR), 0.17; 95% confidence interval (CI), 0.04-0.78; P = 0.023), while no significant differences were observed in small-vessel occlusion (adjusted OR, 0.24; 95% CI, 0.02-2.67; P = 0.248) and undetermined etiology (adjusted OR, 0.53; 95% CI, 0.18-1.55; P = 0.247) subgroups (P for interaction = 0.376). Similar trends were observed for END2, with a significant benefit observed in the large-artery atherosclerosis (adjusted OR 0.24; 95% CI 0.08-0.72; P = 0.011). The early improvement rates and 90-day functional outcomes were comparable between the treatment groups across all stroke subtypes. Safety outcomes were similar between antiplatelet therapies in each subgroup.

In patients who developed ischemic stroke within 24 h of symptom onset, there was no evidence of a treatment interaction across stroke etiologies when comparing intravenous tirofiban to oral aspirin for reducing END. However, the absolute risk reduction observed with tirofiban was greatest in patients with large-artery atherosclerosis compared with those with small-vessel occlusion or undetermined etiology.

Dual antiplatelet therapy (DAPT) is superior to single antiplatelet therapy (SAPT) for secondary prevention after minor, non-cardioembolic stroke. We aimed to assess whether DAPT efficacy is modified by large artery atherosclerotic (LAA) etiology, and DAPT safety by stroke size on MRI.

Post hoc analysis of the Phase 2 PACIFIC-STROKE randomized clinical trial, which enrolled patients with non-cardioembolic stroke, all with baseline MRI and compared the Factor XIa inhibitor asundexian with placebo on a background of DAPT or SAPT. We compared patients treated with DAPT versus SAPT. The efficacy endpoint was the rate of recurrent ischemic stroke, the safety endpoint was major or clinically relevant non-major bleeding during follow-up.

1590 patients were included, median NIHSS was 2 (interquartile range [IQR] 1-4), 40% received DAPT. Median follow-up was 11.5 months. The efficacy endpoint occurred in 4.4% and 4.8% in the DAPT group and SAPT group, respectively, with the strongest numerical benefit of DAPT over SAPT among patients with NIHSS ⩽ 3 not treated by intravenous thrombolysis. LAA index stroke etiology did not modify DAPT treatment effect. The safety endpoint occurred more often in the DAPT than in the SAPT group (4.6% vs 2.7%), with the numerically lowest risk among patients with NIHSS ⩽ 3 not treated by intravenous thrombolysis. Stroke size did not modify the effect of DAPT on the safety endpoint.

We found no evidence of major treatment effect heterogeneity with DAPT compared with SAPT in patients with and without LAA or by stroke size on MR-DWI.

Recent studies have shown that the neutrophil-to-lymphocyte ratio (NLR) can predict short-term and long-term outcomes in acute ischemic stroke (AIS) patients. However, the relationship of the variation of NLR (ΔNLR) with hemorrhage transformation (HT) and early neurological improvement (ENI) after intravenous thrombolysis (IVT) remains unclear. This study aimed to investigate the impact of ΔNLR on HT and ENI at 24 h post-IVT and its association with different TOAST classifications. AIS patients undergoing IVT between October 2021 and October 2023 were enrolled and classified by TOAST criteria. Patients were grouped based on the presence or absence of HT and ENI. Our study demonstrated that both HT and ENI were associated with ΔNLR, which was an independent influencing factor for HT and ENI following IVT. Specifically, the ΔNLR in the small artery occlusion (SAO) group was higher than that in the minor stroke of large artery atherosclerosis (LAA) subtype. Thus, ΔNLR may serve as a useful biomarker to assist in diagnosis and monitor the outcomes of thrombolytic therapy in AIS patients.

The degree of culprit artery stenosis affects the risk of early neurological deterioration (END) after acute ischemic stroke (AIS). The TREND trial demonstrated the efficacy of tirofiban in preventing END in patients with AIS. We aimed to investigate whether the degree of intracranial artery stenosis affects the efficacy of tirofiban in preventing END in patients with AIS.

We conducted a post hoc analysis of the TREND trial, which enrolled patients within 24 h of onset and randomly allocated to receive intravenous tirofiban or oral aspirin. We stratified the stenosis degrees into three subgroups: no stenosis, mild-to-moderate stenosis (stenosis <70%), and severe stenosis or occlusion (stenosis ⩾70%). The primary endpoint is END4 defined as an increase of the NIHSS ⩾4 within 72 h after randomization. Secondary outcomes include END2 (defined as an increase of NIHSS ⩾2) within 72 h after randomization, the proportion of mRS 0-1 and 0-2 at 90 days.

A total of 296 patients were analyzed. In patients with severe stenosis or occlusion, tirofiban significantly reduced the incidence of END4 (5.7% vs 30.8%, adjusted OR 0.156, 95% CI 0.028-0.873, adjusted p = 0.034), whereas its effects in preventing END4 were similar to those of aspirin in patients with no stenosis (2.4% vs 4.6%, adjusted OR 0.193, 95% CI 0.018-2.083, adjusted p = 0.175) or mild-to-moderate stenosis (2.9% vs 10.0%, adjusted OR 0.171, 95% CI 0.015-1.943, adjusted p = 0.155). The p value for interaction between stenosis subgroups and treatment was 0.513. Furthermore, tirofiban significantly reduced the incidence of END2 in patients with mild-to-moderate stenosis (5.9% vs 22.5%, OR 0.146, 95% CI 0.022-0.951, adjusted p = 0.044) and severe stenosis or occlusion (11.4% vs 43.6%, adjusted OR 0.140, 95% CI 0.036-0.540, adjusted p = 0.004). A significant improvement in favorable outcomes with a 90-day mRS of 0-1 was observed only in patients with mild-to-moderate stenosis (85.3% vs 70.0%, adjusted OR 4.617, 95% CI 1.077-19.798, adjusted p = 0.039).

Tirofiban may significantly reduce the incidence of END in patients with severe arterial stenosis or occlusion. Further studies are required to confirm the effects of intracranial artery stenosis on the benefits of intravenous tirofiban.

ClinicalTrials.gov; identifier: NCT04491695.

Anterior circulation stroke (ACS) differs from posterior circulation stroke (PCS) in several aspects. We hypothesize that the risk of early neurologic deterioration (END) and its responses to clopidogrel plus aspirin versus aspirin alone may be different between stroke territories.

This was a prespecified post hoc analysis of ATAMIS (Antiplatelet Therapy in Acute Mild to Moderate Ischemic Stroke) trial and included patients with definite infarct location who were classified into ACS and PCS according to stroke territory. Primary outcome was occurrence of END at 7 days, defined as ≥2-point increase in National Institutes of Health Stroke Scale score compared with baseline. We compared the treatment effects of clopidogrel plus aspirin versus aspirin alone in each stroke territory. From 3000 patients, 2431 eligible patients (1780 with ACS [910 assigned into clopidogrel plus aspirin and 870 assigned into aspirin alone] and 651 with PCS [371 assigned into clopidogrel plus aspirin and 280 assigned into aspirin alone]) were included. Median age was 66 years and 35.1% were women. The occurrence of END was higher in ACS than PCS (6.8% versus 3.8%, P=0.007). clopidogrel plus aspirin was associated with lower risk of END in ACS (risk difference [95% CI]: -2.4% [-4.1% to -0.8%], P=0.004), but not in PCS (risk difference [95% CI]: -0.6% [-2.7% to 1.5%], P=0.57). No significant interaction was found (P=0.69).

Our study demonstrated END was higher in acute mild-to-moderate ischemic stroke with anterior circulation, who derived more benefit from clopidogrel plus aspirin than aspirin alone.

URL: https://www.clinicaltrials.gov; Unique identifier: NCT02869009.

Stroke secondary to intracranial atherosclerotic disease (ICAD) is associated with high recurrence risk despite currently available secondary prevention strategies. In patients with systemic atherosclerosis, a significant reduction of stroke risk with no increase in intracranial or fatal hemorrhage was seen when rivaroxaban 2.5 mg twice daily was added to aspirin. However, there are no trials in ICAD using this combination. To facilitate the design of future ICAD trials, the CATIS-ICAD study (Combination Antithrombotic Treatment for Prevention of Recurrent Ischemic Stroke in Intracranial Atherosclerotic Disease) assessed (1) the feasibility of recruitment, (2) the safety of low-dose rivaroxaban plus aspirin compared with standard-of-care antiplatelet therapy, and (3) trends toward efficacy.

This was a prospective, randomized, open-label, blinded end point pilot trial conducted in 10 Canadian centers. Eligible participants aged ≥40 years, with acute ischemic stroke or high-risk transient ischemic attack, were randomly assigned in a 1:1 ratio to receive low-dose rivaroxaban plus aspirin or aspirin alone within 7 to 100 days of their index event. The primary safety outcome was hemorrhagic stroke. The main efficacy end point was the composite of ischemic stroke or covert brain infarct on magnetic resonance imaging at the end of the study.

A total of 101 participants were randomized. Average enrollment was 10 participants/site per year. Average follow-up was 20 months. Median time from index stroke to randomization was 67 days. The median age of participants was 67 years (±10.94), and 29% of participants were women. There was no hemorrhagic stroke in either arm. The composite efficacy outcome was less frequent in the combination arm (15.7%) compared with the aspirin arm (24.0%), with a hazard ratio of 0.78 ([95% CI, 0.32-1.93]; P=0.59) favoring the intervention.

A multicenter randomized trial comparing the combination of low-dose rivaroxaban and aspirin in patients with recent ischemic stroke or transient ischemic attack due to ICAD is feasible and appears safe without an increased risk of hemorrhagic stroke. A numerical trend toward efficacy for the composite primary end point of symptomatic ischemic stroke and covert infarcts was observed. These findings will inform the design of a phase III trial.

URL: https://www.clinicaltrials.gov; Unique identifier: NCT04142125.

The efficacy and safety of P2Y12 inhibitors (P2Y12i) with aspirin in patients with non-cardioembolic ischemic cerebrovascular events remains a topic of ongoing debate. Therefore, we conducted an updated meta-analysis to compare these drugs with aspirin alone.

We systematically searched PubMed, Embase, and Cochrane Central for randomized controlled trials (RCTs) comparing the two treatment regimens in patients with ischemic cerebrovascular events. Primary outcomes were all-cause mortality, severe bleeding, and stroke recurrence. We performed subgroup analyses stratified by National Institutes of Health Stroke Scale (NIHSS). Risk ratios (RRs) with 95 % confidence intervals were calculated using a random effects model. R software (version 4.3.2) was used for statistical analyses.

Fifteen studies were included, comprising 38,851 patients, of whom 19,483 (50.1 %) received P2Y12i plus aspirin. Follow-up ranged from 7 days to 3.4 years. P2Y12i plus aspirin significantly reduced stroke recurrence (RR 0.78; 95 % CI = 0.71-0.87; p < 0.05), but increased the incidence of all-cause mortality (RR 1.38; 95 % CI = 1.11-1.72; p < 0.05) and severe bleeding (RR 2.07; 95 % CI 1.61 to 2.66; p > 0.05) compared with aspirin. There was no significant difference between groups in all-cause mortality in patients with NIHSS ≤3 or ≤10.

P2Y12i plus aspirin reduced stroke recurrence, but increased all-cause mortality and severe bleeding in patients with non-cardioembolic ischemic events. There was no difference between groups in all-cause mortality in patients with NIHSS scores ≤3 or ≤10.

Sex may impact clinical outcomes in patients with stroke treated with dual antiplatelet therapy (DAPT). We aimed to investigate the sex differences in the short-term outcomes of DAPT within a real-world population of patients with noncardioembolic mild-to-moderate ischemic stroke or high-risk transient ischemic attack.

We performed a propensity score-matched analysis from a prospective multicentric cohort study (READAPT [Real-Life Study on Short-Term Dual Antiplatelet Treatment in Patients With Ischemic Stroke or Transient Ischemic Attack]) by including patients with noncardioembolic mild-to-moderate stroke (National Institutes of Health Stroke Scale score of 0-10) or high-risk transient ischemic attack (age, blood pressure, clinical features, duration of transient ischemic attack, presence of diabetes [ABCD2] ≥4) who initiated DAPT within 48 hours of symptom onset. The primary effectiveness outcome was the 90-day risk of new ischemic stroke or other vascular events. The secondary effectiveness outcomes were the 90-day modified Rankin Scale score ordinal shift, vascular and all-cause mortality, and 24-hour early neurological improvement or deterioration. The safety outcomes included the 90-day risk of moderate-to-severe and any bleeding, symptomatic intracranial hemorrhage, and 24-hour hemorrhagic transformation. Outcomes were compared between sexes using Cox and generalized ordinal logistic regression analyses, along with calculating risk differences and ratios.

From 2278 patients in the READAPT study cohort, we included 1643 mild-to-moderate strokes or high-risk transient ischemic attacks treated with DAPT (mean age, 69.8±12.0 years; 34.3% women). We matched 531 women and men. The 90-day risk of new ischemic stroke or other vascular events was significantly lower among women than men (hazard ratio, 0.53 [95% CI, 0.28-0.99]; P=0.039). There were no significant differences in secondary effectiveness outcomes. The 90-day risk of safety outcomes was extremely low and did not differ between women and men (moderate-to-severe bleedings: 0.4% versus 0.8%; P=0.413; symptomatic intracranial hemorrhage: 0.2% versus 0.4%; P=0.563). Subgroup analysis for primary effectiveness outcome showed a lower 90-day risk of new ischemic stroke or other vascular events among women aged <50 years, baseline National Institutes of Health Stroke Scale score of 0 to 5, prestroke modified Rankin Scale score <2, large artery atherosclerosis cause, and no diabetes.

Our findings suggest that women with noncardioembolic mild-to-moderate stroke or high-risk transient ischemic attack treated with DAPT may have lower short-term risk of recurrent ischemic events than men. Further research is needed to understand the mechanisms behind potential sex-based differences in outcomes after DAPT use.

URL: https://www.clinicaltrials.gov; Unique identifier: NCT05476081.

 Patients with ischemic stroke present a higher risk of stroke recurrence, neurological deterioration, and death. The benefit of dual antiplatelet therapy (DAPT) over single antiplatelet therapy (SAPT) among patients with minor ischemic stroke is well established; however, robust evidence is lacking for those with nonminor stroke.

 To describe the benefits and risks of DAPT versus SAPT in patients with nonminor ischemic stroke.

 We searched the PubMed, Embase, and Cochrane Library databases for articles published from inception to April 2024. Data were collected from randomized clinical trials and observational studies comparing DAPT to SAPT following nonminor ischemic stroke, defined by a score ≥ 4 on the National Institutes of Health Stroke Scale (NIHSS).

 In total, 6 studies were included, comprising 12,480 patients. The NIHSS score at baseline from the selected studies ranged from 4 to 15. There was no significant difference between DAPT and SAPT for recurrent stroke (risk ratio [RR] = 0.91; 95% confidence interval [95%CI] = 0.82-1.01; p = 0.09; I2 = 0%), ischemic stroke (RR = 0.89; 95%CI = 0.80-1.00; p = 0.05; I2 = 0%) or hemorrhagic stroke (RR = 1.23; 95%CI = 0.41-3.99; p = 0.66; I2 = 27%). Major bleeding was not significantly increased in the DAPT group compared with the SAPT group (RR = 0.87; 95%CI = 0.29-2.66; p = 0.81; I2 = 44%). The overall analysis did not show a significant difference in all-cause mortality (RR = 0.72; 95%CI = 0.50-1.02; p = 0.07; I2 = 0%).

 There was no difference between DAPT and SAPT regarding recurrent stroke, ischemic stroke, hemorrhagic stroke, major bleeding, or overall mortality.

Both high-sensitive C-reactive protein (hsCRP) and CYP2C19 genotypes are independent predictors of clinical outcomes after ischemic stroke. We aim to evaluate the association of CYP2C19 loss-of-function alleles (LoFA) carrying status with the effects of dual/single antiplatelet therapy at different hsCRP levels using the CHANCE trial.

Subjects with both of CYP2C19 major alleles information (*2, *3, and *17) and hsCRP measurements were enrolled from the prespecified subgroup. CYP2C19 LoFA carriers were defined as patients with either*2 or *3 allele. Cox proportional hazards models were used to assess the interaction of CYP2C19 LoFA carrying status with the effects of dual/single antiplatelet therapy at different hsCRP levels. The primary outcome was recurrent stroke within 90 days.

Among 2,801 patients, 1,646 (58.8%) were LoFA carriers, and 922 (32.9%) had elevated hsCRP. In patients with nonelevated hsCRP, there was a significant interaction effect between CYP2C19 LoFA carrying status and dual/single antiplatelet regimens for prevention of recurrent stroke and combined vascular events (P = .048, .048, respectively), but, not in patients with elevated hsCRP (P = .502, .472, respectively). Only among patients with nonelevated hsCRP and noncarrier of CYP2C19 LoFA, dual antiplatelets significantly reduced the risk of recurrent stroke compared with aspirin alone (hazard ratio = 0.44 [0.26-0.74], P = .003). No significant differences in bleeding were found.

Nonelevated hsCRP and noncarrier of CYP2C19 LoFA may predict a better response to dual antiplatelet therapy in reducing stroke recurrence and composite vascular events for patients with minor stroke and high-risk TIA.

clinicaltrials.gov Identifier: NCT00979589.

The potential for early white matter hyperintensities(WMH) regression and associated contributory factors remains uncertain. The purpose of this study is to investigate whether WMH regress at early time of three months after minor ischemic stroke (MIS) or transient ischemic attack (TIA), while also identifying factors that may influence this outcome.

A retrospective analysis of a prospective subcohort from the CHANCE trial comprising individuals with MIS and TIA was conducted. All patients underwent brain MRI at the onset and at three months. Deep learning algorithms were employed for the automatic segmentation of WMH volumes in four distinct regions. Scores for lacunes, cerebral microbleeds (CMB), perivascular spaces (PVS), WMH, and overall cerebral small vessel disease (CSVD) burden were quantified. Patients were divided into the stable, regression and progression groups according to change in WMH volume. The demographic, clinical, and imaging data of the participants in the three groups were collected and statistically analyzed.

A total of 98 patients with minor ischemic stroke or TIA were included. There were 22 patients in the stable group, 41 patients in the regression group and 35 patients in the progression group. Age and hypertension status were significantly different among the three groups. The lacunes, CMB,WMH, and total CSVD burden scores differed notably among groups, with all the CSVD markers being severely elevated in the progression group, moderately elevated in the regression group, and subtly elevated in the stable group.

The findings suggest that WMH could exhibit regression within three months following minor ischemic stroke or TIA. Patients under the age of 65, without a hypertension history, and with a low CSVD burden are more likely to experience WMH regression.

Sex-specific differences in stroke risk factors, clinical presentation, and outcomes are well documented. However, little is known about real-world differences in transient ischemic attack (TIA) hospitalizations and outcomes between men and women.

This was a retrospective cohort study of the 2016 to 2021 Nationwide Readmissions Database in the United States. Adult patients hospitalized for TIA were included. Annual incidences of TIA hospitalizations for men and women were calculated using the US Census Bureau data. Primary end points were 90-day readmission for ischemic stroke or hemorrhage and compared between men and women. Demographics and comorbidities were captured and used to adjust for confounders using propensity score matching and logistic regression models.

A total of 588 499 patients were identified; 326 794 (55.5%) were women. The estimated annual incidence of TIA hospitalizations was 42.4 (95% CI, 26.0-58.9) per 100 000 women and 36.2 (95% CI, 23.5-48.9) per 100 000 men (relative risk, 1.17 [95% CI, 1.13-1.21]; P<0.001). Overall, women were older, had higher rates of headache and psychiatric comorbidities, and had lower rates of vascular risk factors compared with men. Women were significantly less likely to be readmitted for ischemic stroke (hazard ratio, 0.86 [95% CI, 0.79-0.93]; P<0.001) and more likely to be readmitted for hemorrhage (hazard ratio, 1.12 [95% CI, 1.04-1.20]; P<0.001), with similar rates of antithrombotic use at the time of readmissions (P>0.05). Compared with ischemic stroke, hemorrhage readmissions were significantly associated with lower odds of home discharge (odds ratio, 0.83 [95% CI, 0.76-0.91]; P<0.001) and higher odds of death (odds ratio, 3.01 [95% CI, 2.35-3.87]; P<0.001).

Women have a higher incidence of TIA hospitalizations than men, which may be due to higher rates of nonischemic causes of transient neurological symptoms as evidenced by differences in baseline characteristics and lower rates of subsequent ischemic stroke. Future studies are needed to better characterize transient neurological symptoms in women to avoid excess hospitalizations and unnecessary treatments that may increase hemorrhage risk.

To evaluate the safety and efficacy of dual antiplatelet therapy (DAPT) versus tenecteplase in minor non-disabling acute ischemic stroke. This retrospective observational study utilized data from our stroke database. All consecutive patients with minor non-disabling acute ischemic stroke treated with either DAPT or tenecteplase between January 2020 and June 2023 were included in the analysis. Of the 62 patients included in the analysis, the median (IQR) age was 66 (58-76) years, and 21 patients (34%) were female. Compared with patients receiving DAPT, those treated with tenecteplase were had higher NIHSS score at treatment (median [IQR], 4 [2-5] vs. 1 [1-2]; P = 0.01). At 90 days, 74.2% of patients (23/31) in the DAPT group and 71.0% (22/31) in the tenecteplase group had an excellent functional outcome (P = 0.78). Lower proportion of patients with minor bleeding events in DAPT group than tenecteplase group (3.2% [1/31] vs. 25.8% [8/31], P = 0.01). The findings in this study show that patients presenting with minor nondisabling acute ischemic stroke within 4.5 h of symptom onset, dual antiplatelet treatment was similar to intravenous tenecteplase with regard to excellent functional outcome at 90 days. However, more proportion of patients with bleeding events treated with tenecteplase.