Abstract Background and aims Perihematomal hypoperfusion has been considered a benign oligoemic state; however, emerging evidence suggests that it may represent an ischemic penumbra with potential progression to irreversible injury. This evolution may result from the combined effects of perfusion abnormalities and neuroinflammatory mediators of secondary brain injury. This study aims to characterize the pathophysiology of perihematomal hypoperfusion. The primary objective is to assess the association between acute-phase perfusion parameters and the development of ischemic lesions in the subacute phase. Secondary objectives are to evaluate the role of plasmatic mediators—including NADPH oxidase, an oxidative stress –related enzyme, and vasoactive molecules (endothelin-1 and nitric oxide)—in the development of perihematomal hypoperfusion and ischemic damage, and to assess their associations with hematoma and edema evolution and clinical outcomes. Imaging and plasmatic biomarkers may identify patients at increased risk of secondary injury. Methods We will enroll 124 patients with spontaneous ICH presenting to the Emergency Department of Umberto I Hospital, Rome, within 12 hours of symptom onset. CT perfusion/angiography will be performed, together with blood sampling for biomarkers analysis. Conventional (Tmax, rCBF/rCBV), microvascular and metabolic (OEF, CMRO2) perfusion parameters will be quantified in the perihematomal hypoperfusion area using Cercare Medical Neurosuite® software. A non-contrast CT at 24 hours will assess hematoma and edema volume evolution. MRI at 7 days will be performed to detect secondary ischemic lesions. Clinical outcome will be assessed by mRS at 3 months. Results The project is under review by the local ethics committee and will be initiated upon approval. Conflict of interest Paolo Amisano: recipient of the HippOnion–ISA AII 2025 Grant. Svetlana Lorenzano: nothing to disclose. Ettore Nicolini: advisory board member for CERCARE Medical and speaker honoraria from Boehringer Ingelheim. Antonio Ciacciarelli: speaker honoraria from the Angels Initiative. Marta Iacobucci: nothing to disclose. Danilo Toni: advisory board participation and speaker’s honoraria from Alexion, AstraZeneca, Boehringer Ingelheim, Medtronic, and Pfizer. Manuela De Michele: nothing to disclose.

Abstract Background and aims WHO reports an increasing burden of cerebrovascular diseases in Sub-Saharan Africa (SSA), with arterial hypertension representing the leading risk factor. Alarmingly, a high prevalence is already observed in childhood. In this context, hypertension may be driven by non-modifiable factors –including genetic predisposition– and lifestyle-related determinants, particularly unhealthy dietary habits. ISA-Africa launched a cardiovascular screening program aimed at identifying pediatric risk factors and promoting early preventive strategies. Methods Between 2024 and 2025, children aged 3–17 years were screened at Monkole Hospital, the referral hospital of Mont Ngafula district, and at the “Elikia” Center, a school for children with disabilities, in Kinshasa, DRC. Data collection included medical history, assessment of nutritional status and blood pressure measurements. Pediatric blood pressure categories were defined according to European Society of Cardiology criteria. Results A total of 183 children (94 males, 89 females; mean age 11.1 ± 3.7 years) were evaluated. 12 children were excluded due to conditions commonly associated with cardiovascular complications, including Down syndrome. Overall, 35.7% of children were classified as hypertensive and 10.5% as pre-hypertensive. Among hypertensive subjects, 52.5% had stage 1 and 47.5% stage 2 hypertension. Regarding nutritional status, 16.4% of children were underweight, 63.7% normal weight, 4.0% overweight, and 12.3% obese. No significant correlations were observed between blood pressure and nutritional status. Conclusions Hypertension prevalence in this pediatric SSA population is markedly higher than previously reported. Providing epidemiological data is essential to clarify the determinants of early-onset hypertension and to support the development of context-specific preventive interventions in SSA. Conflict of interest Paolo Amisano: recipient of the Hipponion ISA-AII research grant (2025). Kasongo Kibambe Michael-Robert: nothing to disclose. Falcou Anne: nothing to disclose. Anna Gardin: nothing to disclose. Manuela De Michele: nothing to disclose.

Abstract Background and aims Transient ischemic attack (TIA) confers a high early risk of subsequent ischemic stroke. Systemic inflammatory activation may contribute to this risk, but the prognostic value of inflammatory indices in TIAs remains unclear. We assessed their association with clinical outcomes and their role in refining ABCD2-based risk stratification. Methods We conducted a multicenter retrospective–prospective observational study including consecutive TIA patients admitted between January 2023 and August 2025. Systemic inflammatory indices (NLR, PLR, LMR, SII, SIRI) were derived from admission blood samples. Primary outcome was 90-day major adverse cardiovascular events (MACE); secondary outcomes included occurrence of stroke or TIA, ischemic stroke, and all-cause mortality up to 12 months. ROC analysis was used to develop a predictive model integrating inflammatory indices with the ABCD2 score (ABCD2-I). Results Among 291 patients included, 10% suffered from 90-day MACE. At multivariable analysis, increasing admission NLR independently predicted 90-day MACE (OR 1.70, 95%CI 1.12–2.58; p = 0.013). NLR was also associated with ischemic stroke or TIA (OR 1.48, 95%CI 1.02–2.13; p = 0.037), while ischemic stroke was independently associated with both NLR (OR 2.74, 95%CI 1.39–5.40; p = 0.003) and PLR (OR 1.01, 95%CI 1.00–1.02; p = 0.029). No inflammatory index predicted mortality. Integration of NLR into the ABCD2 score improved discrimination (AUC 0.605 vs 0.668), with an optimal cut-off of 4. Conclusions In TIA patients, systemic inflammatory burden independently predicts ischemic recurrence, and its integration into ABCD2 improves identification of high-risk patients beyond clinical models. Conflict of interest Marco Andrighetti: nothing to disclose.

Abstract Background and aims Studies from the USA have reported lower access to reperfusion treatments (RTs) for Ischemic Stroke (IS) among racial/ethnic minorities; however, evidence from Italy is lacking. We aimed to assess the impact of race/ethnicity on RTS administration and onset-to-door time (ODT). Methods Consecutive adult patients with IS presenting to 14 Italian stroke centers between October 2024 and November 2025 were prospectively enrolled. Based on self-reported race/ethnicity, patients were classified as White or non-White. Outcomes were Intravenous Thrombolysis (IVT), Endovascular Treatment (EVT), and ODT. Associations between ODT and race/ethnicity were assessed using linear regression adjusted for demographics, comorbidities, baseline NIHSS, premorbid mRS, education level, mode of arrival, occupational status, language barriers, and cohabitation status. Logistic regressions adjusted for the same variables, plus large vessel occlusion, anticoagulant use, and ASPECTs were used to identify predictors of IVT and EVT. Results Overall, 2402 patients were enrolled in the study, of whom 2257 were Whites (94.0%). Overall, 830 patients (35.7%) received IVT and 648 (27.9%) EVT. Compared with White patients, non-White patients were younger (62.9±16.7 vs 74.1±13.9 years; p<0.001) and less frequently women (33.8% vs 47.2%, p=0.002). White category was not associated with IVT and EVT administration (aOR 0.70 95%CI (0.34-1.67), p=0.497 and aOR 2.50 95%CI (0.84-7.40), p=0.098, respectively) but was independently associated with shorter ODT (aβ -631.69 95%CI (-1100.34 - -163.03); p=0.008). Conclusions Our study suggests that racial/ethnic disparities in timely access to stroke care exist even in countries with universal healthcare systems, highlighting the need for public health interventions. Conflict of interest Nothing to disclose

Abstract Background and aims Systemic inflammatory indices have been associated with clinical outcomes in stroke. However, their relationship with the velocity of ischemic core expansion remains unclear. We investigated the association between systemic inflammatory markers and infarct growth rate (IGR) in patients with acute anterior large-vessel occlusion (LVO) ischemic stroke (IS). Methods We conducted a single-center retrospective observational study including consecutive patients admitted with acute anterior LVO IS, within 24 hours from known symptom onset, between January 2023 and August 2025. Ischemic core volume (CBF <30%) and IGR (core volume/onset-to-CT time) were calculated for each patient. Admission systemic inflammatory indices included: neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI). The primary outcome was the fast ischemic core progression, defined as IGR ≥10 mL/h. Secondary outcomes included continuous associations with IGR and relationships with ischemic progression phenotypes (slow, intermediate, fast). Results Among 120 patients included, 77 (64.2%) were classified as fast progressors. Admission NLR was independently associated with rapid ischemic core progression (OR 2.13; 95%CI 1.22–3.70; p = 0.007). Ordinal regression analysis confirmed that higher NLR (OR 1.90; 95%CI 1.19–3.03; p = 0.006) and PLR (OR 1.02; 95%CI 1.01–1.03; p = 0.050) were independently associated with faster ischemic progression phenotypes. In contrast, no significant association was observed between continuous NLR values and IGR. Conclusions Elevated admission NLR independently predicts faster ischemic core progression in anterior circulation LVO stroke, highlighting a pathophysiological link between systemic inflammation and accelerated infarct evolution. Conflict of interest Marco Andrighetti: nothing to disclose.

Abstract Background and aims Cerebral perfusion parameters in acute ischemic stroke(AIS) could help in predicting response to acute treatments. This study aimed to assess temporal changes of perfusion parameters in routine clinical practice in treated patients with AIS and their impact on clinical outcome. Methods In this retrospective observational study, we included patients with AIS treated with IV thrombolysis and/or mechanical thrombectomy. All patients underwent multimodal CT at baseline and MRI within 24 hrs from symptom onset. We used an AI-based neuroimaging software. At the two timepoints, we measured volumes of total hypoperfusion (TH), ischemic core (IC), and mismatch/ischemic penumbra (M/IP). We evaluated impact of perfusion dynamics on clinical outcomes (modified Rankin score [mRS] and mortality at 3 months). Results Overall, 101 patients with AIS were included (women 40.6%, mean[±SD] age of 72.8[±13.3], median baseline NIHSS 8.50). 71.3% of patients had a perfusion parameter improvement/stability pattern with “Imaging/Clinical Post-treatment TIA” occurring in 22.8% of them. We observed a significant difference between median baseline volumes of TH (from 45.90 to 1.0 ml,p<0.001) and M/IP (from 38.80 to 0 ml,p<0.001) and those assessed in the post-treatment. IC reduction after treatment was found in a high proportion of patients(44.6%). We obtained similar results in the three treatment groups. IC and TH percentage changes were independent predictors of mRS and mortality at 3 months. Conclusions Our study demonstrated that IC as determined with the current neuroimaging tools and parameters could also include salvageable brain tissue areas. Conflict of interest Svetlana Lorenzano: nothing to disclose

Abstract Background and aims Stroke mimics account for 30% of all stroke codes; their correct identification may avoid inappropriate treatments and reduce treatment times. Perfusion imaging and derived metabolic parameters may improve differential diagnosis in the emergency setting. We aimed to test the ability of Oxygen Extraction Fraction(OEF) and time to maximum(Tmax), to distinguish ischemic stroke (IS) from stroke mimics. Methods We conducted a 5-month prospective observational study including all consecutive stroke codes admitted within 24 hours of symptom onset, excluding intracranial hemorrhage. All patients underwent CT perfusion analyzed with automated software to generate Tmax and OEF maps. Maps were visually assessed on the symptomatic hemisphere and compared with the contralateral side, then quantitatively confirmed with two symmetrically placed ROIs. OEF was classified as normal or increased (≥2-level rise on the colorimetric scale vs the contralateral area). Tmax maps were categorized as hypoperfusion (Tmax>6s), hyperperfusion (Tmax≤3s), or normoperfusion (Tmax>3s and <6 s). Statistical analysis included Pearson’s χ2 test, Student’s t test, and multivariate logistic regression. Results Among 143 patients, 58% had IS and 42% stroke mimic. Both increased OEF (85.7% vs 14.3%; p<0.001) and Tmax>6s were associated with IS. Logistic regression confirmed increased OEF (aOR 0.21[95%CI 0.07–0.64], p=0.006), but not Tmax (aOR 0.78[95%CI 0.29-2.11], p=0.631), as an independent predictor for ruling out stroke mimic, including after adjustment for NIHSS categories (aOR 0.25[95%CI 0.08–0.84], p=0.025). Conclusions OEF is an independent marker distinguidhing IS from stroke mimics and may improve diagnostic accurancy an management in emergency. Conflict of interest E.N. is member of the medical and scientific advisory board of Cercare Medical and declares speaker's honoraria from Boehringer Ingelheim; A.C. has nothing to disclose; M.A. has nothing to disclose; C.A.F. has nothing to disclose; G.S. has nothing to disclose; A.N. has nothing to disclose; A.F. has nothing to disclose; S.L. has nothing to disclose; M.D. has nothing to disclose; D.T. declares consulting or advisory board fees or speaker’s honoraria from Alexion, ASTRA Zeneca, Boehringer, Medtronic and Pfizer.

Abstract Background and aims Iron deficiency (ID) is associated with worse functional outcomes. The mechanisms underlying this relationship remain unclear. ID may impair microvascular function, potentially affecting cerebral perfusion. We aimed to investigate the association between ID and infarct progression in acute ischemic stroke. Methods We conducted a two-year retrospective observational study including consecutive patients with acute ischemic stroke. All underwent CT or MR perfusion imaging at admission and after 24 hours. ID was defined as ferritin<100 ng/ml or 100-299 ng/ml with transferrin saturation TSAT<20%. Perfusion parameters included ischemic core volume (CBF < 30%), hypoperfusion intensity ratio (HIR, Tmax>10s/Tmax>6 s), and infarct growth rate (IGR, ischemic core volume divided by onset-to-imaging time). Correlations between TSAT and perfusion metrics were adjusted for age and sex. Clinical outcomes included NIHSS, mRS, and hemorrhagic transformation. Results Among 382 patients (median age 76 years; 44.2% women), 58.8% had ID. Patients with ID showed significantly higher infarct growth (IGR 0.81 vs 0.44; P = 0.034). TSAT correlated inversely with IGR (r = −0.136, P = 0.035; 95% CI −0.258 to −0.010) and HIR (r = −0.213, P = 0.005; 95% CI −0.352 to −0.064). These associations remained significant after adjustment for age and sex. Clinically, patients with ID had higher NIHSS scores and worse functional outcomes at discharge and at 90 days. Conclusions ID in acute ischemic stroke is associated with accelerated infarct growth, more severe hypoperfusion patterns, and poorer neurological outcomes, supporting a potential pathophysiological role of iron status in infarct evolution and prognosis. Conflict of interest The authors declare no conflicts of interest.

Abstract Background and aims Risk factors for Ischemic Stroke (IS) and adherence to primary prevention strategies may differ substantially across racial/ethnic groups. However, available evidence derives from the USA, where the racial/ethnic composition differs from that of Europe. The primary aim of our study was to investigate racial/ethnic differences in the prevalence of stroke risk factors and primary prevention therapies in Italy. Methods Consecutive adult patients with IS presenting to 14 Italian stroke centers between October 2024 and November 2025 were prospectively enrolled. Based on self-reported race/ethnicity, patients were classified as White or non-White. Outcomes were the prevalence of stroke risk factors and preventive therapies in use at stroke onset. The Mann-Whitney U-test and χ2-test were used for statistical comparisons. To identify independent associations between race/ethnicity and stroke risk factors, multivariable logistic regression models adjusted for sex and age were performed. Results Overall, 2402 patients were enrolled in the study, of whom 2257 were Whites (94.0%). Compared with White patients, non-White patients were younger (62.9±16.7 vs 74.1±13.9 years; p<0.001) and less frequently women (33.8% vs 47.2%, p=0.002). Cardiopathy (p=0.037), dyslipidaemia (p=0.016), and atrial fibrillation (p=0.001) were more prevalent among White patients, whereas non-White patients more frequently reported no ongoing therapy at admission (p<0.001). However, after adjustment for age and sex, White race was not independently associated with any of these factors. Conclusions Non-White patients experience ischemic stroke at a younger age than White patients, potentially reflecting earlier exposure to cardiovascular risk factors and lower awareness of them and their management. Conflict of interest Nothing to disclose

INTRODUCTION:International guidelines recommend only non-contrast CT (NCCT) for eligible acute ischemic stroke (AIS) patients receiving intravenous thrombolysis (IVT) in the early time window. We aim to assess the potential role of advanced neuroimaging in predicting radiological and clinical outcomes in AIS patients treated with IVT within 4.5 h of stroke onset. METHODS:Between July 2021 and August 2022, 262 AIS patients within 4.5 h underwent multimodal CT protocol (NCCT, CT-perfusion using RAPID software, multiphasic CT-Angiography). Demographic, clinical, and neuroradiological data, including CT-perfusion parameters were collected. Final infarct volume (FIV) and 3-month clinical outcomes using modified Rankin Scale (mRS) were assessed. RESULTS:Patients with unfavourable 3-month outcome (mRS 3-6) were older, had higher baseline National Institutes of health Stroke Scale (NIHSS), a longer onset-to-needle time and a higher percentage of Baseline Alberta stroke programme early CT score (ASPECTS) ≤9. All perfusional parameters were notably more impaired in patients with 3-month unfavourable outcome. Patients with 3-month mRS 3-6 had a larger FIV at follow-up (p < 0.001). In multivariable binomial logistic regression model ischemic core as relative Cerebral Blood Flow (rCBF) < 30 % (p < 0.001), baseline NIHSS (p = 0.020) and TICI 0-2a (p = 0.005) independently predicted FIV > 10 ml. Age (p < 0.001), baseline NIHSS (p = 0.026), onset to needle time (p = 0.004) and rCBF<30 % (p = 0.005) independently predicted 3-month mRS 0-2. In multivariable ordinal logistic regression model rCBF<30 % was an independent predictor of 3-month mRS 3-6 (OR 1.04, p = 0.001). CONCLUSION:In the early time window for IVT, the rCBF<30 % as ischemic core is a useful early predictor of FIV and 3-month clinical outcome.

BACKGROUND AND PURPOSE:Understanding the causes of recurrent ischemic events in patients with minor stroke or high-risk TIA is crucial to understand unmet needs in secondary prevention. This study examines the characteristics and causes of recurrences after non-cardioembolic minor stroke/high-risk TIA in patients treated with the best medical care. METHODS:This subgroup analysis from a prospective real-world study (READAPT, NCT05476081) included patients with non-cardioembolic minor ischemic stroke (NIHSS ≤5) or TIA (ABCD2 score ≥ 4), receiving short-term DAPT. We described the etiologic distribution according to the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification of the index and of the recurrent event. We analyzed baseline characteristics of patients with and without a 90-day ischemic recurrence to identify factors linked to recurrence. RESULTS:Out of 1641 patients, 56 (3.4 %) had a recurrent ischemic event (35 strokes and 21 TIAs). The cause of recurrences was undetermined in 21 (37.5 %), small vessel occlusion in 18 (32.1 %), large artery atherosclerosis in 11 (19.6 %), other determined in 3 (5.4 %), and cardioembolism in 3 (5.4 %). The etiologic distribution of recurrent events differed from that of the corresponding index events (p = 0.002). Non-compliance to DAPT was more prevalent in patients with recurrences compared with those without (8.9 % vs 3.7 %, p = 0.048). CONCLUSIONS:Patients with recurrences after a minor stroke or high-risk TIA have a different etiologic distribution compared with their index events. Additionally, a lower compliance to DAPT was observed in those with recurrences, suggesting that adherence to DAPT should be encouraged to optimize the outcome of patients.

ImportanceThe net clinical effect of early vs later direct oral anticoagulant (DOAC) initiation after atrial fibrillation–associated ischemic stroke is unclear.ObjectiveTo investigate whether early DOAC treatment is associated with a net clinical benefit (NCB).Design, Setting, and ParticipantsThis was a post hoc analysis of the Early Versus Late Initiation of Direct Oral Anticoagulants in Post–Ischaemic Stroke Patients With Atrial Fibrillation (ELAN) open-label randomized clinical trial conducted across 103 sites in 15 countries in Europe, the Middle East, and Asia between November 6, 2017, and September 12, 2022, with a 90-day follow-up. Participants included patients with atrial fibrillation–associated acute ischemic stroke, excluding those with therapeutic anticoagulation at stroke onset or with severe hemorrhagic transformation of the ischemic infarct.InterventionEarly DOAC initiation (<48 hours after minor and moderate stroke, 6-7 days after major stroke) vs later initiation (3-4 days after minor stroke, 6-7 days after moderate stroke, and 12-14 days after major stroke).Main Outcomes and MeasuresThe main measure was the NCB of early treatment over later treatment, calculated by subtracting the weighted rate of excess bleeding events (major extracranial or intracranial hemorrhage) attributable to early treatment from the rate of excess ischemic events (recurrent stroke or systemic embolism) possibly prevented by early treatment within 30 days (main analysis) or 90 days (ancillary analysis). An established weighting scheme was used to account for the different clinical impact of bleeding relative to ischemic outcomes. Event rates were derived from adjusted logistic models. The analysis included all evaluable randomized ELAN participants.ResultsOf the original 2013 ELAN participants, 1966 were eligible for analysis (977 [49.7%] assigned to early DOAC initiation, 989 [50.3%] assigned to later DOAC initiation; median [IQR] age 77 [70-84] years; 1075 [54.7%] male). The 30-day NCB of early treatment over later treatment ranged from 1.73 (95% CI, 0.06-3.40) to 1.72 (95% CI, −0.63 to 3.98) weighted events possibly prevented per 100 participants for intracranial hemorrhage weights 1.5 to 3.3. The 90-day NCB ranged from 2.16 (95% CI, 0.30-3.87) to 2.14 (95% CI, −0.26 to 4.41) weighted events per 100 participants.Conclusions and RelevanceThis post hoc analysis of a randomized clinical trial estimated a sizeable NCB of early anticoagulation for patients after atrial fibrillation–associated ischemic stroke. Although estimates cannot exclude the possibility of no benefit or small net harm, the findings suggest that early treatment may be more favorable.Trial RegistrationClinicalTrials.gov Identifier: NCT03148457

Patients with ischemic stroke (IS) or TIA face an elevated cardiovascular risk, warranting intensive lipid-lowering therapy. Despite recommendations, adherence to guidelines is suboptimal, leading to frequent undertreatment. This study aims to evaluate the statin use after IS and TIA. LIPYDS is a multicenter, observational, retrospective study including ≥ 18-year-old patients discharged after IS/TIA from 19 Italian centers in 2021. Multivariable logistic regression analysis was used to determine (1) the association between statin prescription (Any-statin versus No-statin), type (High-Intensity-statin versus Other-statin [Moderate/Low-Intensity]) with stroke etiology (TOAST), (2) clinical variables independently associated with statin prescription in the entire cohort and within TOAST categories. We included 3,740 patients (median age 75 [IQR 64–82]; median LDL-C 104 [IQR 79–131]). At discharge, 1,971 (52.7

BACKGROUND AND AIM:According to randomized controlled trials (RCTs), dual antiplatelet therapy (DAPT) is more effective for secondary prevention of ischemic events attributable to large artery atherosclerosis (LAA) than other mechanisms. We investigated whether real-world application may impact DAPT effectiveness and safety in the REAl-life study on short-term Dual Antiplatelet treatment in Patients with ischemic stroke or Transient ischemic attack (READAPT, NCT05476081). METHODS:READAPT was an observational multicenter study including patients with minor ischemic stroke or TIA treated with short-term DAPT. At 90 days, we assessed primary effectiveness (ischemic recurrence, severe bleeding, or vascular death) and safety (severe to moderate bleeding) outcomes. We explored associations between LAA and outcomes using Cox regression. Within patients with and without LAA, outcomes were compared between subgroups based on age, NIHSS score (for ischemic stroke patients), ABCD2 score (for TIA patients), presence and number of MRI acute lesions, and DAPT regimen characteristics. RESULTS:Among 1920 analyzed patients (of 2278 enrolled), 452 had LAA. Unlike RCTs, 21.2% of patients with LAA had NIHSS > 5, and 48.2% received DAPT > 30 days. Patients with LAA had higher bleeding rates (3.5% vs. 2.1%, p = 0.004), primarily hemorrhagic infarctions and moderate bleeding, than those without LAA. However, primary effectiveness outcomes were similar (4.9% vs. 3.5%, p = 0.201) between the groups. In patients with LAA, prolonged DAPT (> 21 days), multiple MRI lesions, age ≥ 65, and loading doses increased bleeding risk. CONCLUSIONS:The real-world DAPT use in patients with LAA exceeds RCTs boundaries with possible drawbacks on treatment safety.

Background: Dual antiplatelet therapy (DAPT) is a cornerstone of secondary prevention in patients with minor ischemic stroke or high-risk transient ischemic attack. The effectiveness and safety of DAPT may differ between patients with posterior (PCI) and anterior circulation infarct (ACI). Objectives: We aimed to compare short-term outcomes following DAPT between mild-to-moderate stroke patients with PCI versus ACI. Design: Propensity-matched analysis from a prospective real-world multicentric cohort study (READAPT). Methods: We included patients with noncardioembolic mild-to-moderate stroke (National Institute of Health Stroke Scale of 0–10) who initiated DAPT within 48 h of symptom onset. Patients were categorized into ACI or PCI based on the infarct(s) location on brain neuroimaging. The primary effectiveness outcome was the 90-day risk of ischemic stroke or other vascular events. The secondary effectiveness outcomes were the 90-day modified Rankin Scale (mRS) score distribution, 24-h early neurological improvement or deterioration, and all-cause mortality. The safety outcomes included the 90-day risk of any bleedings and 24-h hemorrhagic transformation. Results: We matched 281 PCI patients with 651 ACI patients. The 90-day risk of ischemic stroke or other vascular events was low and similar between PCI and ACI groups (3.1% vs 2.9%, respectively; hazard ratio 0.98, (95% confidence interval (CI) 0.45–2.14); p = 0.845). Patients with PCI had worse 90-day mRS ordinal distribution compared to those with ACI (odds ratio 1.18 (95% CI 1.01–1.39); p = 0.046). There were no differences in other secondary outcomes. Safety outcomes had low incidence and did not differ between groups (any bleedings: 3.2% vs 2.6%; 24-h hemorrhagic transformation: 1.8% vs 1.2%). We found no differences in the risk of ischemic stroke or other vascular events between patients with PCI and ACI across subgroups defined by sex, age, presumed stroke etiology, stroke severity, prestroke mRS, hypertension, diabetes, acute reperfusion therapies, DAPT loading dose, or presence of symptomatic intracranial stenosis. Conclusion: Our findings suggest that effectiveness and safety outcomes after DAPT in patients with mild-to-moderate noncardioembolic ischemic stroke are consistent regardless of infarct location in the anterior or posterior circulation territory. However, patients with PCI may experience worse short-term functional outcome. Trial registration: URL: www.clinicaltrials.gov ; Unique identifier: NCT05476081.

INTRODUCTION:Patients with ischemic stroke or transient ischemic attack (TIA) and cancer face unique risks of recurrent ischemic events and bleeding. It is unclear whether this increased risk is present even in patients with minor ischemic stroke or transient ischemic attack (TIA) receiving dual antiplatelet therapy (DAPT). This study aimed to evaluate the impact of cancer on the short-term outcomes after DAPT in patients with non-cardioembolic minor ischemic stroke or high-risk TIA. PATIENTS AND METHODS:This was a secondary analysis of the prospective multicentric READAPT study (NCT05476081), including patients with non-cardioembolic minor ischemic stroke (NIHSS ⩽ 5) or high-risk TIA (ABCD2 ⩾4) who initiated DAPT within 48 h of symptom onset. The primary effectiveness outcome was the 90-day risk of new ischemic stroke or other vascular events (TIA, myocardial infarction, death due to vascular causes). Secondary outcomes included 90-day mRS score distribution and all-cause mortality. The primary safety outcome was the 90-day risk of any bleeding, with secondary safety outcomes including 24-h hemorrhagic transformation. We used Inverse Probability Weighting to compare outcomes between patients with and without cancer. RESULTS:From 2278 patients in the READAPT study cohort, we included 1561 patients (mean age 70.3 ± 11.7 years; 65.4% males), of whom 206 (13.2%) had cancer, categorized as either active (27.7%) or in remission (72.3%). After weighting, overall cancer patients had a higher risk of 90-day new ischemic stroke or other vascular events (weighted HR 1.78, 95% CI 1.20-2.63, p = 0.004) and worse 90-day mRS score distribution (OR 1.24, 95% CI 1.10-1.41, p < 0.001) compared to patients without cancer. The 90-day risk of bleeding did not differ between cancer and no-cancer groups overall. When analyzing cancer subgroups, patients with active cancer had significantly higher risk of 90-day ischemic stroke or other vascular (weighted HR 2.75, 95% CI 1.70-4.45, p < 0.001) and any bleeding (weighted HR 2.51, 95% CI 1.27-4.97, p = 0.008) events compared to no-cancer patients. In contrast, patients with cancer in remission had comparable risks to those without cancer. Furthermore, hematological malignancies were associated with a substantially higher risk of 90-day new ischemic stroke or other vascular events compared to solid tumors (weighted HR 8.15, 95% CI 5.06-13.14, p < 0.001). CONCLUSIONS:Patients with minor ischemic stroke or high-risk TIA and active cancer have increased risk of ischemic and bleeding events after DAPT. Conversely, patients with cancer in remission have similar outcomes compared to those with no cancer.

Background:Elevated baseline systolic blood pressure (SBP) was associated with poor outcomes following dual antiplatelet therapy (DAPT) in patients with non-cardioembolic minor ischemic stroke (MIS) or high-risk transient ischemic attack (TIA) in clinical trials. Objectives:We aimed to assess the impact of admission SBP on the short-term outcomes after DAPT in patients with non-cardioembolic MIS or high-risk TIA. Methods:We performed an inverse probability weighted (IPW) analysis from a prospective multicentric real-world study (READAPT) including patients with non-cardioembolic MIS (National Institute of Health Stroke Scale of 0-5) or high-risk TIA (ABCD2 ⩾4) who initiated DAPT within 48 h 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, 24-h early neurological improvement or deterioration. The safety outcomes included the 90-day risk of moderate-to-severe and any bleedings, symptomatic intracranial hemorrhage, and 24-h hemorrhagic transformation. We used Cox proportional hazards regression with restricted cubic splines to model the continuous relationship between SBP and the hazard ratio (HR) of new vascular events. We selected SBP = 124 mm Hg as cut-off point for the IPW weighting. Outcomes were compared using Cox and generalized logistic regression analyses, adjusted for residual confounders. Results:From 2278 patients in the READAPT cohort, we included 1291 MIS or high-risk TIAs (mean age 70.6 ± 11.4 years; 65.8% males). After IPW, patients with admission SBP ⩾124 mm Hg versus <124 mm Hg had a significantly higher risk of 90-day ischemic stroke or other vascular events (adjusted HR: 2.14 (95% CI 1.07%-4.98%); p = 0.033) and of 24-h early neurological deterioration (adjusted risk difference: 1.91% (95% CI 0.60%-3.41%); p = 0.006). The overall risk of safety outcomes was low, although patients with SBP ⩾124 mm Hg on admission showed higher rates of 90-day moderate-to-severe and any bleeding events (adjusted risk difference: 1.24% (95% CI 0.38%-2.14%); p = 0.004 and 6.18% (95% CI 4.19%-8.16%); p < 0.001; respectively), as well as of 24-h hemorrhagic transformation (adjusted risk difference: 1.57% (95% CI 0.60%-2.55%); p = 0.001). Subgroup analysis showed a significant interaction between admission SBP, sex, and time to DAPT start in predicting 90-day new vascular events (p for interaction <0.001 and 0.007, respectively). Conclusion:In patients with non-cardioembolic MIS or high-risk TIA, higher levels of admission SBP may be associated with an increased risk of new vascular events, early neurological deterioration, and bleeding after DAPT use. Future studies should further investigate if optimizing blood pressure management may further improve prognosis.

BACKGROUND AND AIMS:Iron deficiency (ID) is a prognostic factor in heart failure and acute coronary syndrome. However, its role in cerebrovascular diseases is controversial. We aimed to determine the impact of ID on the functional outcome of acute ischemic stroke patients. METHODS:This was an observational prospective multicentric cohort study. From January to December 2023, we enrolled acute ischemic stroke patients admitted to the stroke units of four comprehensive stroke centers. Venous blood samples were collected at admission to determine the iron status (serum iron, ferritin, transferrin). ID was defined as a serum ferritin concentration < 100 ng/mL or 100-299 ng/mL with transferrin saturation (TSAT) <20 %. The primary endpoint was the poor functional outcome at 90 days defined as modified Rankin Scale (mRS) 3-6. We used binary logistic regression models including confounding factors to test the association between ID and the primary outcome. RESULTS:The analysis included 442 patients (mean age 73 ± 13, 47.5 % female, median NIHSS 7 [IQR 3-15], 61.3 % treated with intravenous thrombolysis and/or endovascular treatment). ID prevalence was 65.6 %. In all binary logistic regression models, ID predicted poor functional outcome at 3 months irrespective from demographics, stroke severity and characteristics, anemia, risk factors, signs/symptoms of heart failure, glucose at admission, and inflammatory biomarkers (aOR 2.328, 95 % CI 1.272-4.263, p = 0.006). CONCLUSIONS:ID was strongly associated with poor functional outcome at 90 days in acute ischemic stroke patients. Further research is required to explore whether iron supplementation could be a potential therapeutic strategy to improve patient outcomes.

BACKGROUND:The outcomes of minor ischemic stroke resulting from small artery occlusion (SAO-MIS) have not yet been characterized after dual antiplatelet treatment (DAPT) has become the standard of care. We provided updated figures on the short-term prognosis of SAO-MIS treated with early short-term DAPT and compared the outcomes of SAO-MIS versus non-SAO-MIS patients. METHODS:This is a prespecified sub-analysis from a prospective multicentric real-world study (READAPT, NCT05476081) including patients with minor (NIHSS≤5) non-cardioembolic ischemic stroke treated with DAPT. The primary outcome was a composite of 90-day symptomatic ischemic stroke or major cardiovascular events. Secondary outcomes were the 90-day ordinal distribution of modified Rankin Scale (mRS) scores, 90-day excellent functional outcome (mRS of 0 to 1), and 24-h early neurological deterioration (END). Safety outcomes were 90-day intracerebral hemorrhage, moderate-to-severe and any bleedings. All outcomes were compared between SAO-MIS and non-SAO-MIS patients. RESULTS:We included 678 MIS, of whom 253 (37.3 %) were SAO-related. At 90 days, 3 patients with SAO-MIS had primary outcome (1.2 % [95 % CI 0.2 %-3.5 %]), which were all SAO-related ischemic strokes. For the secondary outcomes, most SAO-MIS patients (n = 191, 75.5 %) had 90-day excellent functional outcome and 12 had 24-h END (4.7 % [95 % CI 2.5 %-8.3 %]). Referring to safety outcomes, 90-day intracerebral hemorrhage occurred only in one patient with SAO-MIS (0.4 % [95 % CI 0.0 %- 2.2 %]). Compared to non-SAO-MIS, the 90-day risk of recurrent vascular events was significantly lower among SAO-MIS (aHR 0.24 [95 % CI 0.08-0.68]; p = 0.007), while there were not significant differences in other secondary outcomes, nor in the risk of safety events. CONCLUSIONS:Our findings show overall favorable short-term prognosis after SAO-MIS treated with DAPT. Future studies should investigate factors associated with residual stroke risk and long-term outcomes of SAO-MIS.

BACKGROUND: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. METHODS: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. RESULTS: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. CONCLUSION: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.