Acute Noncardioembolic Ischemic Stroke Research Articles

Hemorrhagic Transformation in Noncardioembolic Acute Ischemic Stroke: MRI Analysis From PACIFIC-STROKE.

In the phase 2 PACIFIC-STROKE trial (Proper Dosing and Safety of the Oral FXIa Inhibitor BAY 2433334 in Patients Following Acute Noncardioembolic Stroke), asundexian, an oral factor XIa inhibitor, did not increase the risk of hemorrhagic transformation (HT). In this secondary analysis, we aimed to investigate the frequency, types, and risk factors of HT on brain magnetic resonance imaging (MRI). This was a secondary analysis of the PACIFIC-STROKE trial. Patients with mild-to-moderate acute noncardioembolic ischemic stroke were randomly assigned to asundexian or placebo plus guideline-based antiplatelet therapy. Brain MRIs were required at baseline (≤120 hours after stroke onset) and at 26 weeks or end-of-study. HT was defined using the Heidelberg classification and classified as early HT (identified on baseline MRI) or late HT (new HT by 26 weeks) based on iron-sensitive sequences. Multivariable logistic regression models were used to test factors that are associated with early HT and late HT, respectively. Of 1745 patients with adequate baseline brain MRI (mean age, 67 years; mean National Institutes of Health Stroke Scale score, 2.8), early HT at baseline was detected in 497 (28.4%). Most were hemorrhagic infarctions (hemorrhagic infarction type 1: 15.2%; HI2: 12.7%) while a few were parenchymal hematomas (parenchymal hematoma type 1: 0.4%; parenchymal hematoma type 2: 0.2%). Early HT was more frequent with longer symptom onset-to-MRI interval. Male sex, diabetes, higher National Institutes of Health Stroke Scale large (>15 mm) infarct size, cortical involvement by infarct, higher number of acute infarcts, presence of chronic brain infarct, cerebral microbleed, and chronic cortical superficial siderosis were independently associated with early HT in the multivariable logistic regression model. Of 1507 with follow-up MRI, HT was seen in 642 (42.6%) overall, including 361 patients (23.9%) with late HT (new HT: 306; increased grade of baseline HT: 55). Higher National Institutes of Health Stroke Scale, large infarct size, cortical involvement of infarct, and higher number of acute infarcts predicted late HT. About 28% of patients with noncardioembolic stroke had early HT, and 24% had late HT detectable by MRI. Given the high frequency of HT on MRI, more research is needed on how it influences treatment decisions and outcomes.

Dyslipidaemia In Acute Non-Cardioembolic Ischemic Stroke Patients At A Tertiary Care Center

Objective: To determine the frequency of dyslipidaemia in acute non-cardio embolic ischemic stroke patients at a tertiary care centre in Rawalpindi. Study Design: Cross-sectional study Place and Duration of Study: Neurology Department, Pak Emirates Military Hospital (PEMH), Rawalpindi Pakistan, Jul 2022 to Feb 2023. Methodology: Patients with acute non-cardio embolic ischemic stroke were included. Data was collected from the patient files and hospital records including a thorough history, physical examination information, CT/MRI brain, fasting lipid profiles with total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG). Results: The study included 196 patients, of which dyslipidaemia was seen with a major share of high TG in 44(22.44%), followed by high LDL cholesterol in 38(19.38%), and high TC was found in 28(14.28%). Conclusion: More than 1/3rd of patients with acute non-cardioembolic ischemic stroke have dyslipidaemia.

Abstract WMP2: A Randomized, Double-Blind, Placebo-Controlled, Phase II Trial in Acute Non-Cardioembolic Ischemic Stroke With Adrenomedullin

Background: Adrenomedullin (AM), a vasoactive peptide, has strong anti-inflammatory and angiogenic properties, which have been reported to ameliorate the consequences of ischemic stroke (IS) in several animal models. This phase II clinical trial aimed to test the safety and tolerability of intravenous (IV) AM administration in acute IS (AIS) patients within 24 hours of onset. Methods: The AdrenoMedullin For Ischemic Stroke study is an investigator-initiated, randomized, double-blind, phase II trial. Patients with non-cardioembolic IS within 24 hours after stroke onset and baseline NIH Stroke Scale (NIHSS) score ≥1 were randomly allocated to the intermittent IV AM (I-AM group) (30 μg/kg in total for 7 days, n=20) or placebo group (n=10) in the first cohort and a combination of continuous (the first 3 days) and intermittent (the following 4 days) IV AM (C/I-AM group) (56 μg/kg in total for 7 days, n=20) or placebo group (n=10) in the second cohort. The primary endpoint was serious adverse events related to the protocol treatment and secondary efficacy endpoints were favorable outcomes (mRS 0-2 at 90 days) and good outcomes (mRS 0-3 at 90 days). Results: The population of 60 patients had a median age of 75 years, 21 patients (35%) were female, and the median NIHSS score was 3. The primary endpoint did not occur in all groups. In the secondary efficacy endpoints, the rates of favorable outcome (75.0% vs. 68.9%, adjusted odds ratio [aOR], 1.45; 95% confidential interval [CI], 0.32-6.53) and good outcome (90.0% vs. 73.7%, aOR 3.86; 95% CI, 0.67-22.11) in the I-AM group were not statistically different from those in the placebo group. The rates of good outcomes in the C/I-AM group were comparable with those in the placebo group (85.0% vs. 73.7%, aOR 1.56; 95% CI, 0.72-3.39). Conclusions: Treatment with IV AM within 24 hours of AIS onset is safe. Intermittent IV AM may contribute to improved AIS prognosis. The efficacy and safety of AM will need confirmation in the next phase of clinical trials.

Asundexian: an oral small moleculefactor XIa inhibitor for the treatment of thrombotic disorders.

Oral anticoagulants, including warfarin and direct oral anticoagulants, are the standard of care for thrombosis prevention and treatment; however, concerns of bleeding often dictate treatment decisions. Inhibition of the intrinsic coagulation system via factor XIa may allow for selective inhibition of the coagulation cascade without significantly impacting hemostasis after injury. Asundexian is an oral small moleculefactor XIa inhibitor that, via this novel mechanism, may prove to be a safe and effective option compared with available anticoagulants. Early clinical data forasundexian was promising as a safer alternative to current therapiesand prompted further analysis incertainpatient populations atincreasedthrombotic risk. Currently, studies areongoing to evaluate thesafety and efficacy in stroke prevention in atrial fibrillation and in patients following an acute noncardioembolic ischemic stroke or high-risk transient ischemic attack.

A Nomogram for Predicting the Recurrence of Acute Non-Cardioembolic Ischemic Stroke: A Retrospective Hospital-Based Cohort Analysis.

Non-cardioembolic ischemic stroke (IS) is the predominant subtype of IS. This study aimed to construct a nomogram for recurrence risks in patients with non-cardioembolic IS in order to maximize clinical benefits. From April 2015 to December 2019, data from consecutive patients who were diagnosed with non-cardioembolic IS were collected from Lanzhou University Second Hospital. The least absolute shrinkage and selection operator (LASSO) regression analysis was used to optimize variable selection. Multivariable Cox regression analyses were used to identify the independent risk factors. A nomogram model was constructed using the "rms" package in R software via multifactor Cox regression. The accuracy of the model was evaluated using the receiver operating characteristic (ROC), calibration curve, and decision curve analyses (DCA). A total of 729 non-cardioembolic IS patients were enrolled, including 498 (68.3%) male patients and 231 (31.7%) female patients. Among them, there were 137 patients (18.8%) with recurrence. The patients were randomly divided into training and testing sets. The Kaplan-Meier survival analysis of the training and testing sets consistently revealed that the recurrence rates in the high-risk group were significantly higher than those in the low-risk group (p < 0.01). Moreover, the receiver operating characteristic curve analysis of the risk score demonstrated that the area under the curve was 0.778 and 0.760 in the training and testing sets, respectively. The nomogram comprised independent risk factors, including age, diabetes, platelet-lymphocyte ratio, leukoencephalopathy, neutrophil, monocytes, total protein, platelet, albumin, indirect bilirubin, and high-density lipoprotein. The C-index of the nomogram was 0.752 (95% CI: 0.705~0.799) in the training set and 0.749 (95% CI: 0.663~0.835) in the testing set. The nomogram model can be used as an effective tool for carrying out individualized recurrence predictions for non-cardioembolic IS.

Abstract WP177: Effects Of The Oral Factor XIa Inhibitor Asundexian On Intracranial Bleeding Among Patients With Acute Non-Cardioembolic Ischemic Stroke: PACIFIC-Stroke Randomized Trial

Introduction: The phase 2 PACIFIC-Stroke trial of patients with acute non-cardioembolic ischemic stroke assessed asundexian, the oral small molecule Factor XIa inhibitor, versus placebo administered within 48h of ischemic stroke to prevent recurrent stroke. This trial uniquely included moderate and severe strokes, which were excluded from other early timeframe, secondary prevention trials of escalated antithrombotic therapy. The primary results suggest a reduction in recurrent ischemic stroke and TIA when added to antiplatelet therapy without an overall increase in intracranial hemorrhage (ICH)(in press at the Lancet ). In this post-hoc analysis, we will further characterize the observed ICH. Methods: PACIFIC-Stroke (NCT04304508) was an international, double-blind, placebo-controlled, phase 2 randomized trial enrolling 1808 participants and comparing three dosages (10mg, 20mg, or 50mg daily) of asundexian with placebo. Participants were randomized within 48h of the qualifying ischemic stroke, and all received background antiplatelet therapy chosen by the local investigator. Eligibility for Part A was limited to patients with NIHSS &lt;/=7 who did not receive thrombolysis or endovascular thrombectomy, and Part B allowed an NIHSS up to 15 and treatment with reperfusion therapy (if &gt;24 hours prior to randomization). Participants underwent MRIs within 72 hours of randomization and after 6 months. Results: In this presentation, we will further characterize the ICHs observed in the 1808 participants (1334 asundexian, 452 placebo) of the PACIFIC-Stroke trial. Further characterization will include timing, baseline stroke severity, post-thrombolysis/endovascular therapy status, asundexian dosing, and associated symptoms and radiological subtypes will be presented. Conclusions: Early anticoagulation of ischemic stroke patients with asundexian added to antiplatelet therapy was not associated with an increase in ICH compared to placebo, supporting the premise that inhibition of Factor XIa may prevent thrombosis without increasing bleeding. Further characterization of the observed ICHs associated with this novel drug compared to placebo will be presented.

Multiple Antiplatelet Therapy in Ischemic Stroke Already on Antiplatelet Agents Based on the Linked Big Data for Stroke.

Optimal antiplatelet strategy for patients with ischemic stroke who were already on single antiplatelet therapy (SAPT) remains to be elucidated. This study aimed to evaluate the effect of different antiplatelet regimens on vascular and safety outcomes at 1 year after non-cardioembolic stroke in patients previously on SAPT. We identified 9,284 patients with acute non-cardioembolic ischemic stroke that occurred on SAPT using linked data. Patients were categorized into three groups according to antiplatelet strategy at discharge: 1) SAPT; 2) dual antiplatelet therapy (DAPT); and 3) triple antiplatelet therapy (TAPT). One-year outcomes included recurrent ischemic stroke, composite outcomes (recurrent ischemic stroke, myocardial infarction, intracerebral hemorrhage, and death), and major bleeding. Of 9,284 patients, 5,565 (59.9%) maintained SAPT, 3,638 (39.2%) were treated with DAPT, and 81 (0.9%) were treated with TAPT. Multiple antiplatelet therapy did not reduce the risks of 1-year recurrent stroke (DAPT, hazard ratio [HR], 1.08, 95% confidence interval [CI], 0.92-1.27, P = 0.339; TAPT, HR, 0.71, 95% CI, 0.27-1.91, P = 0.500) and 1-year composite outcome (DAPT, HR, 1.09, 95% CI, 0.68-1.97, P = 0.592; TAPT, HR, 1.46, 95% CI, 0.68-1.97, P = 0.592). However, the TAPT groups showed an increased risk of major bleeding complications (DAPT, HR, 1.23, 95% CI, 0.89-1.71, P = 0.208; TAPT, HR, 4.65, 95% CI, 2.01-10.74, P < 0.001). Additional use of antiplatelet agents in patients with non-cardioembolic ischemic stroke who were already on SAPT did not reduce the 1-year incidence of vascular outcomes, although it increased the risk of bleeding complications.

Dual Antiplatelet Therapy in the Management of Acute Minor Ischemic Stroke and High-Risk Transient Ischemic Attack: An Expert Consensus Statement From Taiwan Stroke Society and Taiwan Society of Emergency Medicine.

The aim of this review is to achieve a consensus between Taiwan Stroke Society (TSS) and Taiwan Society of Emergency Medicine (TSEM) to manage acute non-cardioembolic minor ischemic stroke (MIS) and high-risk transient ischemic attack (TIA). The methodology is to review the recent findings from clinical trials of dual antiplatelet therapy (DAPT) from 2010 to 2021 and updates in clinical practice guidelines from 2018 to 2022 for non-cardioembolic MIS/TIA management at the acute stage. Four leading clinical studies, CHANCE, POINT, THALES, and CHANCE-2 along with other relevant studies introducing DAPT, are discussed in this review. The risk-benefit profile between stroke recurrence reduction and major bleeding increase is also elucidated. TSS and TSEM concluded that for patients presenting with non-cardioembolic MIS or high-risk TIA who did not receive intravenous alteplase, initiation of DAPT within 24 hours after stroke onset and continued up to 21 days, followed by antiplatelet monotherapy, is effective in reducing recurrent ischemic stroke for a period of up to 90 days.

Dual antiplatelet treatment for minor acute ischemic stroke and high-risk transient ischemic attack: have we reached the limit of antithrombotic management?

In this issue of the European Journal of Internal Medicine Pomero et al. present their systematic review and meta-analysis evaluating the early use of clopidogrel and ticagrelor in addition to aspirin for the treatment of patients presenting with an acute non-cardioembolic minor acute ischemic stroke or transient ischemic attack (TIA) [1].

P2Y12 inhibitors plus aspirin for acute treatment and secondary prevention in minor stroke and high-risk transient ischemic attack: A systematic review and meta-analysis

BackgroundAspirin is a cornerstone of preventive treatment for stroke recurrence, but during the last few years the role of dual antiplatelet therapy (DAPT) is much more emerging. ObjectiveThis systematic review aimed to compare early use of P2Y12 inhibitors (clopidogrel/ticagrelor) plus aspirin to aspirin alone for acute treatment and secondary prevention in acute non-cardioembolic minor ischemic stroke or TIA. MethodsA systematic search on MEDLINE and EMBASE was performed. Treatment effects were estimated with RRs and 95% CI. We used RevMan 5.4 for data analyses. We assessed methodological quality of selected studies according to Rob2 tools and quality of evidence with GRADE approach. ResultsFour RCTs were included, enrolling 21,459 patients. Compared to aspirin alone, DAPT was superior in reducing stroke recurrence (RR 0.74, 95% CI 0.67–0.82, P <0.00001, absolute risk difference by 2%, NNT 50) and disabling stroke defined as mRS>2 (RR 0.84, 95% CI 0.75–0.95, P = 0.004), with no impact on all causes of mortality (RR 1.30, 95% CI 0.90–1.89, P = 0.16). An increased risk of major bleeding was emerged (RR 2.54, 95% CI 1.65–3.92, P <0.0001, absolute risk difference by 0,4%, NNH 250), in particular with ticagrelor, but there was no correlation between therapy duration and bleeding risk, as appeared from one-month (RR 3.06, 95% CI 1.64 to 5.69) and three-month (RR 2.09, 95% CI 1.18 to 3.69) follow-up analysis. ConclusionsEarly administration of P2Y12 inhibitors plus aspirin in patients with acute non-cardioembolic minor ischemic stroke or TIA reduced the incidence of ischemic stroke recurrence, impacting more significantly than the increased bleeding risk and influencing patients’ quality of life by reducing disabling stroke.

Dyslipidemia in Acute Non-cardioembolic Ischemic Stroke Patients at a Tertiary Care Centre: A Descriptive Cross-sectional Study.

Acute ischemic stroke is the second most common cause of death after ischemic heart disease worldwide and Nepal's top five diseases based on Disability-Adjusted Life Years. Dyslipidemia is a major risk factor for coronary heart disease but has an unclear role in the pathogenesis of ischemic stroke. The objective of this study was to find the prevalence of dyslipidemia in acute non-cardioembolic ischemic stroke patients at a tertiary care centre. A descriptive cross-sectional study was conducted among 76 patients with acute noncardioembolic ischemic stroke admitted in the Neuromedicine unit of a tertiary care centre from August 2017 to July 2018. Ethical approval was obtained from the Institutional Review Committee of the same institute (Reference number: 478/2020). Patients underwent baseline investigations, including fasting lipid profile and Computed Tomography Scan/Magnetic Resonance Imaging head. Data were analysed using Statistical Package for the Social Sciences version 21.0. Point estimate at 95% Confidence Interval was calculated along with frequency and proportion for binary data. The prevalence of dyslipidemia among the acute non-cardioembolic ischemic stroke patients was 35 (46.05%) (35.05-57.05 at 95% Confidence Interval) where high total cholesterol was diagnosed in 11 (31.43%), high triglycerides in 25 (71.43%), high low-density-lipoprotein in 10 (28.57%), and low high-density-lipoprotein in 11 (31.43%) patients. The prevalence of dyslipidemia among acute non-cardioembolic ischemic stroke patients at our tertiary care centre is higher than the similar studies done in similar settings. cardioembolic stroke; dyslipidemia; ischemic stroke; lipid; lipoprotein.

Low-Molecular-Weight Heparin Versus Aspirin in Early Management of Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

ObjectivesTo evaluate the difference between low-molecular-weight heparin (LMWH) and aspirin in preventing early neurological deterioration (END) and recurrent ischemic stroke (RIS), post-recovery independence, and safety outcomes in acute ischemic stroke.Materials and MethodsWe performed systematic searches of the PubMed, Embase, Web of Science, and Cochrane Library databases for full-text articles of randomized controlled trials (RCTs) of LMWH vs. aspirin in the early management of acute ischemic stroke. Information on study design, eligibility criteria, baseline information, and outcomes was extracted. Synthesized relative risks (RRs) with 95% confidence intervals (CIs) are used to present the differences between the two treatments based on fixed-effects models.ResultsFive RCTs were retrieved from the online databases. The results showed no significant difference in efficacy outcomes between the two groups among unselected patients. Subgroup analysis showed that LMWH was significantly related to a lower incidence of END events [relative risk (RR): 0.44, 95% confidence interval (CI): 0.35–0.56] and reduced occurrence of RIS during treatment (OR: 0.34, 95% CI: 0.16–0.75) in non-cardioembolic stroke. LMWH significantly increased the number of patients with a modified Rankin scale (mRS) score of 0–1 at 6 months in patients with large-artery occlusive disease (LAOD) (RR: 0.50, 95% CI: 0.27–0.91). LMWH had a similar effect on symptomatic intracranial hemorrhage (sICH) and major extracranial hemorrhage during treatment to that of aspirin, except that LMWH was related to an increased likelihood of extracranial hemorrhage.ConclusionsIn patients with acute non-cardioembolic ischemic stroke, especially that with large-artery stenosis, LMWH treatment significantly reduced the incidence of END and RIS, and improved the likelihood of independence (mRS 0–1) at 6 months compared with those with aspirin treatment. LMWH was related to an increased likelihood of extracranial hemorrhage among all patients; however, the difference in major extracranial hemorrhage and sICH was not significant. Choosing the appropriate patients and paying attention to the start time and duration of treatment are very important in the use of anticoagulation.Systematic Review Registration http://www.crd.york.ac.uk/PROSPERO, identifier CRD42020185446.

Ischemic Benefit and Hemorrhage Risk of Ticagrelor-Aspirin Versus Aspirin in Patients With Acute Ischemic Stroke or Transient Ischemic Attack.

In patients with acute mild-moderate ischemic stroke or high-risk transient ischemic attack, the THALES trial (Acute Stroke or Transient Ischemic Attack Treated With Ticagrelor and Aspirin for Prevention of Stroke and Death) demonstrated that when added to aspirin, ticagrelor reduced stroke or death but increased risk of severe hemorrhage compared with placebo. The primary efficacy outcome of THALES included hemorrhagic stroke and death, events also counted in the primary safety outcome. We sought to disentangle risk and benefit, assess their relative impact, and attempt to identify subgroups with disproportionate risk or benefit. In a randomized, placebo-controlled, double-blind trial of patients with mild-to-moderate acute noncardioembolic ischemic stroke or high-risk transient ischemic attack, patients were randomized within 24 hours after symptom onset to a 30-day regimen of either ticagrelor plus aspirin or matching placebo plus aspirin. For the present analyses, we defined the efficacy outcome, major ischemic events, as the composite of ischemic stroke or nonhemorrhagic death, and defined the safety outcome, major hemorrhage, as intracranial hemorrhage or hemorrhagic death. Net clinical impact was defined as the combination of these 2 end points. In 11 016 patients (5523 ticagrelor-aspirin and 5493 aspirin), a major ischemic event occurred in 294 patients (5.3%) in the ticagrelor-aspirin group and in 359 patients (6.5%) in the aspirin group (absolute risk reduction 1.19% [95% CI, 0.31%–2.07%]). Major hemorrhage occurred in 22 patients (0.4%) in the ticagrelor-aspirin group and 6 patients (0.1%) in the aspirin group (absolute risk increase 0.29% [95% CI, 0.10%–0.48%]). Net clinical impact favored ticagrelor-aspirin (absolute risk reduction 0.97% [95% CI, 0.08%–1.87%]). Findings were similar when different thresholds for disability were applied and over a range of predefined subgroups. In patients with mild-moderate ischemic stroke or high-risk transient ischemic attack, ischemic benefits of 30-day treatment with ticagrelor-aspirin outweigh risks of hemorrhage. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03354429.

P2Y12 receptor inhibitor plus aspirin versus aspirin treated within 24 hours of acute noncardioembolic ischemic stroke or TIA: Meta-analysis

Antiplatelet therapy is the cornerstone for acute ischemic stroke or transient ischemic attack (TIA). The purpose of this study was to conduct a meta-analysis to assess the efficacy and safety of P2Y12 receptor inhibitor plus aspirin versus aspirin alone treated within 24h after acute noncardioembolic ischemic stroke or TIA. We search Pubmed, EMBASE, CENTRAL and clinicaltrials.gov from January 1966 to January 2021. We included randomized trials which compared P2Y12 receptor inhibitor plus aspirin versus aspirin alone. Relative risk (RR) with 95% confidence (CI) was used as a measure of P2Y12 receptor inhibitor plus aspirin versus aspirin. The primary efficacy endpoint was recurrent stroke and the primary safety endpoint was severe bleeding. The search identified 5 randomized trials comparing P2Y12 receptor inhibitor plus aspirin and aspirin with 21,808 individuals enrolled. Pooled results from these trials showed that P2Y12 receptor inhibitor plus aspirin compared with aspirin was associated with a lower risk of recurrent stroke (RR 0.75, 95% CI 0.68 to 0.83). Ticagrelor plus aspirin compared with aspirin was associated with increased risk of severe bleeding (RR 3.98, 95% CI 1.74 to 9.10) and intracranial hemorrhage (RR 3.32, 95% CI 1.33 to 8.25), whereas clopidogrel plus aspirin vs. aspirin had similar hemorrhagic risk. P2Y12 receptor inhibitor plus aspirin vs aspirin given within 24h after acute noncardioembolic ischemic stroke or TIA reduces the risk of subsequent stroke. However, the risk of severe bleeding, including intracranial hemorrhage, was higher with ticagrelor plus aspirin vs aspirin. CRD42020203730.

Meta-Analysis of Usefulness of Antiplatelet Therapy in Ischemic Stroke or Transient Ischemic Attack

The efficacy of early administration of dual antiplatelet therapy (DAPT) for secondary prevention after acute ischemic stroke or transient ischemic attack (TIA) is uncertain. This systematic review and meta-analysis compares the safety and efficacy of early administration (<24 hours) of DAPT (using either clopidogrel or ticagrelor with aspirin) versus single antiplatelet therapy (SAPT; aspirin alone) in acute non-cardioembolic ischemic stroke or TIA, incorporating data from large randomized controlled trials. Published trials fulfilling our criteria were identified from an electronic search of MEDLINE, with key words including: "clopidogrel or ticagrelor", "aspirin", "ischemic stroke", "transient ischemic attack", and "randomized controlled trial". Included were 3 randomized controlled trials of 21,067 patients assessing early administration (<24 hours from symptom onset) of DAPT versus SAPT in non-cardioembolic acute ischemic stroke or TIA. Our efficacy outcomes were ischemic stroke and all-cause mortality. Our safety outcome was severe bleeding. We performed a meta-analysis to pool results with a hierarchical Bayesian random-effects model. Dual antiplatelet therapy significantly reduced the risk of ischemic stroke (hazard ratio [HR], 0.73; 95% credible interval [CrI]: 0.54, 0.97), while increasing the risk of severe bleeding (HR, 2.48; 95% CrI: 1.07, 5.26). There was a non-significant numerical trend toward increased mortality with DAPT (HR, 1.29; 95% CrI: 0.73, 2.23). These observations were robust under the sensitivity analysis. In the present systematic review and meta-analysis of randomized controlled trials, DAPT reduced the risk of ischemic stroke at the cost of an increase in severe bleeding. Additional trials examining the ideal timing of DAPT administration are needed to thoroughly investigate the role, if any, of routine DAPT in patients with non-cardioembolic ischemic stroke or high-risk TIA.

Antiplatelet Therapy in the Secondary Prevention of Non-cardioembolic Ischemic Stroke and Transient Ischemic Attack: A Mini-Review.

The aim of this mini-review is to discuss the main antiplatelet agents that have been successfully used in the secondary prevention of non-cardioembolic ischemic stroke and transient ischemic attacks (TIA). The methodology is based on a literature review of available peer-reviewed English studies listed in PubMed. The findings reveal that aspirin remains a reliable antiplatelet agent in the secondary prevention of acute non-cardioembolic ischemic stroke and TIA. Nevertheless, currently, there are also other agents, i.e., ticagrelor, clopidogrel, and cilostazol, that can be applied. In addition, the results indicate that time is significant not only in severe stroke but also in non-severe stroke and TIA, which suggests that antiplatelet therapy should be applied within 24 h after the first symptoms because early treatment can lead to an improvement in neurological outcomes and reduce the chance of an early subsequent stroke.

Association between Brachial-Ankle Arterial Stiffness and Cerebral Small Vessel Disease Load in Patients with Acute NonCardioembolic Ischemic Stroke

Association between Brachial-Ankle Arterial Stiffness and Cerebral Small Vessel Disease Load in Patients with Acute NonCardioembolic Ischemic Stroke

Ticagrelor and Aspirin or Aspirin Alone in Acute Ischemic Stroke or TIA

BackgroundTrials have evaluated the use of clopidogrel and aspirin to prevent stroke after an ischemic stroke or transient ischemic attack (TIA). In a previous trial, ticagrelor was not better than aspirin in preventing vascular events or death after stroke or TIA. The effect of the combination of ticagrelor and aspirin on prevention of stroke has not been well studied.MethodsWe conducted a randomized, placebo-controlled, double-blind trial involving patients who had had a mild-to-moderate acute noncardioembolic ischemic stroke, with a National Institutes of Health Stroke Scale (NIHSS) score of 5 or less (range, 0 to 42, with higher scores indicating more severe stroke), or TIA and who were not undergoing thrombolysis or thrombectomy. The patients were assigned within 24 hours after symptom onset, in a 1:1 ratio, to receive a 30-day regimen of either ticagrelor (180-mg loading dose followed by 90 mg twice daily) plus aspirin (300 to 325 mg on the first day followed by 75 to 100 mg daily) or matching placebo plus aspirin. The primary outcome was a composite of stroke or death within 30 days. Secondary outcomes were first subsequent ischemic stroke and the incidence of disability within 30 days. The primary safety outcome was severe bleeding.ResultsA total of 11,016 patients underwent randomization (5523 in the ticagrelor–aspirin group and 5493 in the aspirin group). A primary-outcome event occurred in 303 patients (5.5%) in the ticagrelor–aspirin group and in 362 patients (6.6%) in the aspirin group (hazard ratio, 0.83; 95% confidence interval [CI], 0.71 to 0.96; P=0.02). Ischemic stroke occurred in 276 patients (5.0%) in the ticagrelor–aspirin group and in 345 patients (6.3%) in the aspirin group (hazard ratio, 0.79; 95% CI, 0.68 to 0.93; P=0.004). The incidence of disability did not differ significantly between the two groups. Severe bleeding occurred in 28 patients (0.5%) in the ticagrelor–aspirin group and in 7 patients (0.1%) in the aspirin group (P=0.001).ConclusionsAmong patients with a mild-to-moderate acute noncardioembolic ischemic stroke (NIHSS score ≤5) or TIA who were not undergoing intravenous or endovascular thrombolysis, the risk of the composite of stroke or death within 30 days was lower with ticagrelor–aspirin than with aspirin alone, but the incidence of disability did not differ significantly between the two groups. Severe bleeding was more frequent with ticagrelor. (Funded by AstraZeneca; THALES ClinicalTrial.gov number, NCT03354429.)

Impact of Sleep-Disordered Breathing on Functional Outcomes in Ischemic Stroke: A Cardiopulmonary Coupling Analysis.

Cardiopulmonary coupling (CPC) analysis is an easily assessable method to evaluate sleep-disordered breathing (SDB); however, its prognostic impact in patients with acute ischemic stroke needs to be investigated. We performed a CPC analysis using Holter monitoring at the early stage of noncardioembolic ischemic stroke to investigate the prognostic effect of SDB on functional impairment at the 3-month follow-up. A total 615 patients with acute noncardioembolic ischemic stroke who underwent Holter monitoring within 30 days of stroke onset were enrolled from a multicenter, prospective, all-comer cohort. CPC analysis was conducted, and SDB was defined by the presence of narrow-band coupling during sleep time. We investigated the association between SDB and functional impairment at 3 months as measured by the modified Rankin Scale. Narrow-band coupling was present in 191 (31.1%) of 615 patients (mean age 64.5±12.6 years). The narrow-band group showed a significantly higher rate of severe functional impairment (modified Rankin Scale score >2; 45.5% versus 12.9%, P<0.001) and persistent disability (Δmodified Rankin Scale score ≤0; 53.9% versus 39.8%, P<0.001) at the 3-month follow-up. In multivariate analysis, narrow-band coupling was an independent predictor of higher risk of severe and persistent functional impairment at 3 months (odds ratio, 3.98 [95% CI, 2.34-6.78]; P<0.001; and odds ratio, 1.81 [95% CI, 1.23-2.66]; P<0.001, respectively). The results remained consistent after propensity-score matched analysis with 157 patient pairs (C-statistic=0.770). SDB assessed by CPC analysis at the early stage of ischemic stroke could predict severe and prolonged functional impairment at 3 months. CPC analysis using Holter monitoring can help predicting functional impairment in acute ischemic stroke.

Therapeutic-induced hypertension in patients with noncardioembolic acute stroke.

To evaluate the safety and efficacy of induced hypertension in patients with acute ischemic stroke. In this multicenter randomized clinical trial, patients with acute noncardioembolic ischemic stroke within 24 hours of onset who were ineligible for revascularization therapy and those with progressive stroke during hospitalization were randomly assigned (1:1) to the control and intervention groups. In the intervention group, phenylephrine was administered intravenously to increase systolic blood pressure (SBP) up to 200 mm Hg. The primary efficacy endpoint was early neurologic improvement (reduction in NIH Stroke Scale [NIHSS] score of ≥2 points during the first 7 days). The secondary efficacy endpoint was a modified Rankin Scale score of 0 to 2 at 90 days. Safety outcomes included symptomatic intracranial hemorrhage/edema, myocardial infarction, and death. In the modified intention-to-treat analyses, 76 and 77 patients were included in the intervention and control groups, respectively. After adjustment for age and initial stroke severity, induced hypertension increased the occurrence of the primary (odds ratio 2.49, 95% confidence interval [CI] 1.25-4.96, p = 0.010) and secondary (odds ratio 2.97, 95% CI 1.32-6.68, p = 0.009) efficacy endpoints. Sixty-seven (88.2%) patients of the intervention group exhibited improvements in NIHSS scores of ≥2 points during induced hypertension (mean SBP 179·7 ± 19.1 mm Hg). Safety outcomes did not significantly differ between groups. Among patients with noncardioembolic stroke who were ineligible for revascularization therapy and those with progressive stroke, phenylephrine-induced hypertension was safe and resulted in early neurologic improvement and long-term functional independence. NCT01600235. This study provides Class III evidence that for patients with acute ischemic stroke, therapeutic-induced hypertension increases the probability of early neurologic improvement.