Effect of Stroke Severity on Efficacy and Safety of Indobufen versus Aspirin in Patients with Moderate to Severe Stroke: Results from the INSURE Randomized Clinical Trial.

Aims: Stroke severity may affect the benefits and safety of antiplatelet therapies. We aimed to investigate whether the efficacy and safety of indobufen versus aspirin were affected by stroke severity.

Methods: We compared the efficacy and safety of indobufen versus aspirin in patients with NIHSS scores of 4-6, 7-9, and 10-18.

Colchicine for preventing stroke in patients with and without intracranial atherosclerotic stenosis: a prespecified analysis of a randomized clinical trial.

Background: The effect of colchicine on subsequent stroke among patients with and without symptomatic intracranial artery stenosis (sICAS) and whether age modifies such effect are not known.

Methods: In this prespecified subgroup analysis of CHANCE-3, a randomized, double-blind, placebo-controlled clinical trial conducted at 244 centers in China between 11 August 2022 and 13 April 2023 (ClinicalTrials.gov number, NCT05439356), we included 7567 patients with ischemic stroke or transient ischemic attack and assessments of intracranial arteries at baseline.

Endovascular Treatment in Patients with Large Vessel Occlusion Stroke of Different Mechanisms.

Introduction: Acute ischemic stroke with large vessel occlusion (AIS-LVO) is mainly caused by in situ thrombosis (IST), artery-to-artery embolism (AAE), and cardioembolism (CE). The clinical characteristics and prognosis of each mechanism are unclear in a real-world scenario.

Methods: We retrospectively analyzed patients with AIS-LVO who underwent endovascular treatment (EVT) between April 2023 and August 2024.

Prognostic Impact of 1-Year Changes in Creatinine- and Cystatin C-Based Estimated Glomerular Filtration Rate After Stroke on 5-Year Outcomes: Insights From the Third China National Stroke Registry.

Background: The impact of long-term renal function change on stroke outcomes remains unclear. This study used the CNSR-III (Third China National Stroke Registry) cohort to determine whether changes in estimated glomerular filtration rate based on creatinine and cystatin C (eGFR) during the first year post stroke were associated with 5-year stroke outcomes.

Methods And Results: We included 4270 patients with centrally tested serum creatinine and cystatin C at admission and 1 year post admission and evaluated 5-year follow-up data.

Dual antiplatelet therapy with ticagrelor vs clopidogrel in patients with TIA or minor stroke with or without symptomatic carotid artery stenosis: a post hoc analysis of the CHANCE-2 trial.

Background And Purpose: Symptomatic internal carotid artery stenosis (sCAS) is an essential cause of transient ischaemic attack (TIA) or minor stroke. We aimed to evaluate whether the superiority of aspirin-ticagrelor over aspirin-clopidogrel varies between patients with sCAS or not.

Methods: This was a post-hoc analysis of the High-Risk Patients with Acute Nondisabling Cerebrovascular Events-II (CHANCE-2) trial, all of which were loss-of-function alleles carriers.

Accelerated biological aging increases the risk of short- and long-term stroke prognosis in patients with ischemic stroke or TIA.

Background: Biological age (BA), an integrated measure of physiological aging, has a clear link to stroke. There is a paucity of long-term longitudinal studies about the association between accelerated biological age and stroke prognosis in patients with previous strokes, and the differences in the predictive ability of various BA indicators calculated from clinical biochemistry biomarkers for future stroke outcomes are still unknown. To evaluate the role of three accelerated BA indicators for short- and long-term prognosis of patients with ischemic stroke or transient ischemic attack (TIA), and to identify the most appropriate predictor.

Stroke Prognosis: The Impact of Combined Thrombotic, Lipid, and Inflammatory Markers.

Aim: D-dimer, lipoprotein (a) (Lp(a)), and high-sensitivity C-reactive protein (hs-CRP) are known predictors of vascular events; however, their impact on the stroke prognosis is unclear. This study used data from the Third China National Stroke Registry (CNSR-III) to assess their combined effect on functional disability and mortality after acute ischemic stroke (AIS).

Methods: In total, 9,450 adult patients with AIS were enrolled between August 2015 and March 2018.

The joint association of lipoprotein(a) and lipoprotein-associated phopholipase A2 with the risk of stroke recurrence.

Background And Purpose: Currently little is known about the joint association of lipoprotein (a) [Lp(a)] and lipoprotein-associated phospholipase A2 (Lp-PLA2) with stroke recurrence.

Methods: In this prospective multicenter cohort study, 10,675 consecutive acute ischemic stroke (IS) and transient ischemic attack (TIA) patients with Lp(a) and Lp-PLA2 were enrolled. The association of stroke recurrence within 1 year with Lp(a) and Lp-PLA2 was assessed using Cox proportional hazards models and Kaplan-Meier curves.

Colchicine in patients with acute ischaemic stroke or transient ischaemic attack (CHANCE-3): multicentre, double blind, randomised, placebo controlled trial.

Objectives: To assess the efficacy and safety of colchicine versus placebo on reducing the risk of subsequent stroke after high risk non-cardioembolic ischaemic stroke or transient ischaemic attack within the first three months of symptom onset (CHANCE-3).

Design: Multicentre, double blind, randomised, placebo controlled trial.

Setting: 244 hospitals in China between 11 August 2022 and 13 April 2023.

The Influence of Non-High-Density Lipoprotein Cholesterol on the Efficacy of Genotype-Guided Dual Antiplatelet Therapy in Preventing Stroke Recurrence.

Background And Purpose: Non-high-density lipoprotein cholesterol (non-HDL-C), which represents the total cholesterol content of all pro-atherogenic lipoproteins, has recently been included as a new target for lipid-lowering therapy in high-risk atherosclerotic patients in multiple guidelines. Herein, we aimed to explore the relationship between non-HDL-C level and the efficacy and safety of ticagrelor-aspirin versus clopidogrel-aspirin in preventing stroke recurrence.

Methods: This study comprised a post hoc analysis of the CHANCE-2 (Ticagrelor or Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events II) trial, from which 5,901 patients with complete data on non-HDL-C were included and categorized by median non-HDL-C levels, using a cutoff of 3.

Immediate- or Delayed-Intensive Statin in Acute Cerebral Ischemia: The INSPIRES Randomized Clinical Trial.

Importance: Comparisons are limited for immediate-intensive and delayed-intensive statin for secondary stroke prevention and neuroprotection in patients with acute mild ischemic stroke or transient ischemic attack (TIA) from atherosclerosis.

Objective: To estimate whether immediate-intensive statin therapy is safe and can lower the risk of recurrent stroke compared with delayed-intensive statin in patients with acute mild ischemic stroke or high-risk TIA from atherosclerosis.

Design, Setting, And Participants: The Intensive Statin and Antiplatelet Therapy for High-Risk Intracranial or Extracranial Atherosclerosis (INSPIRES) trial, a double-blind, placebo-controlled, 2 × 2 factorial, randomized clinical trial enrolled patients from September 2018 to October 2022.

Efficacy and safety of Ferrous iron on the prevention of Vascular cOgnitive impaiRment among patients with cerebral Infarction/TIA (FAVORITE): rationale and design of a multicentre randomised trial.

Background: The incidence of vascular cognitive impairment (VCI) is high in patients suffering from ischaemic stroke or transient ischaemic attack (TIA) or with vascular risk factors. Effective prevention strategies for VCI remain limited. Anaemia or low haemoglobin was found as an independent risk factor for adverse outcomes after acute stroke.

Elevated gut microbiota metabolite bile acids confer protective effects on clinical prognosis in ischemic stroke patients.

Background: There is evidence of an association between the gut microbiota and progression of stroke. However, the relationship between gut microbial metabolites, specifically bile acids (BAs), and post-ischemic stroke disability and poor functional outcomes remains unexplored.

Methods: Patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA) in the Third China National Stroke Registry were grouped according to total bile acid (TBA) quartile on admission.

Plasma Soluble Angiotensin-Converting Enzyme 2 and Risk of Recurrent Stroke: A Nested Case-Control Analysis.

Introduction: The angiotensin-converting enzyme 2 (ACE-2) and its shedding product (soluble ACE-2 [sACE-2]) are implicated in adverse cardiovascular outcomes. However, the relationship between sACE-2 and stroke recurrence is unknown. Herein, we examined the relationship of sACE-2 with stroke recurrence in patients with ischemic stroke or transient ischemic attack.

LDL-C Levels and Bleeding Risk in Patients Taking DAPT After Minor Ischemic Stroke or TIA.

Importance: Evidence on the bleeding risk associated with low-density lipoprotein cholesterol (LDL-C) levels in patients receiving dual antiplatelet therapy (DAPT) remains sparse.

Objective: To investigate the association of LDL-C levels with bleeding risk in patients with minor ischemic stroke (MIS) or high-risk transient ischemic attack (HRTIA) receiving DAPT.

Design, Setting, And Participants: This cohort study was an analysis of pooled data from 2 randomized, double-blind, placebo-controlled clinical trials in China of patients with MIS or HRTIA who were receiving DAPT: the CHANCE (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events) trial enrolled patients at 114 sites from October 2009 to July 2012, and the CHANCE-2 enrolled patients at 202 centers from September 2019 to March 2021.

Impact of alkaline phosphatase on clinical outcomes in patients with ischemic stroke: a nationwide registry analysis.

Background: Data on the association between serum alkaline phosphatase (ALP) levels and clinical outcomes in patients with ischemic stroke (IS) are inconsistent and limited. Therefore, this study aimed to investigate the correlation between ALP and prognosis in patients with IS.

Methods: Patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA) from the Third China National Stroke Registry were divided into four groups according to the quartiles of serum ALP levels on admission.

Blood Pressure Partially Mediated the Association of Insulin Resistance and Cerebral Small Vessel Disease: A Community-Based Study.

Background: Insulin resistance as a significant vascular risk factor has been studied in relation to cerebral small vessel disease (SVD). Evidence suggests that insulin resistance might trigger high blood pressure (BP). Therefore, we aimed to investigate whether insulin resistance impacts SVD with a mediating effect of BP in nondiabetic subjects.

Differential effect of ticagrelor versus clopidogrel by homocysteine levels on risk of recurrent stroke: a post hoc analysis of the CHANCE-2 trial.

Background: Elevated homocysteine levels are associated with increased blood coagulation and platelet activity and may modulate the response to antiplatelet therapies. We aimed to investigate the effects of homocysteine levels on the efficacy and safety of ticagrelor-acetylsalicylic acid (ASA) versus clopidogrel-ASA among patients with minor stroke or transient ischemic attack who carried loss-of-function alleles.

Methods: We conducted a post hoc analysis of the CHANCE-2 (The Clopidogrel in High-risk Patients with Acute Nondisabling Cerebrovascular Events-II) trial.

Efficacy and safety of dual antiplatelet therapy in the elderly for stroke prevention: a subgroup analysis of the CHANCE-2 trial.

Objectives: Evidence of the optimal antiplatelet therapy for elderly patients who had a stroke is limited, especially those elder than 80 years. This study aimed to explore the efficacy and safety of dual antiplatelet therapy (DAPT) in old-old patients compared with younger patients in the ticagrelor or Clopidogrel with aspirin in High-risk patients with Acute Non-disabling Cerebrovascular Events-II (CHANCE-2) trial.

Methods: CHANCE-2 was a randomised, double-blind, placebo-controlled trial in China involving patients with high-risk transient ischaemic attack or minor stroke with CYP2C19 loss-of-function alleles.

One-Year Outcomes of Early Therapy With Ticagrelor vs Clopidogrel in Loss-of-Function Carriers With Stroke or TIA Trial.

Background And Objectives: The Ticagrelor or Clopidogrel with Aspirin in High-Risk Patients with Acute Nondisabling Cerebrovascular Events II (CHANCE-2) trial showed that among Chinese patients with minor ischemic stroke or transient ischemic attack (TIA) who were carriers of loss-of-function alleles, dual-antiplatelet therapy with ticagrelor-aspirin reduced the 90-day risk of stroke without increased severe or moderate bleeding compared with clopidogrel-aspirin. However, whether dual-antiplatelet therapy with ticagrelor was superior to clopidogrel beyond the 90 days of follow-up remained unclear. In this study, we reported 1-year follow-up outcomes of the CHANCE-2 trial.

Dual Antiplatelet Treatment up to 72 Hours after Ischemic Stroke.

Background: Dual antiplatelet treatment has been shown to lower the risk of recurrent stroke as compared with aspirin alone when treatment is initiated early (≤24 hours) after an acute mild stroke. The effect of clopidogrel plus aspirin as compared with aspirin alone administered within 72 hours after the onset of acute cerebral ischemia from atherosclerosis has not been well studied.

Methods: In 222 hospitals in China, we conducted a double-blind, randomized, placebo-controlled, two-by-two factorial trial involving patients with mild ischemic stroke or high-risk transient ischemic attack (TIA) of presumed atherosclerotic cause who had not undergone thrombolysis or thrombectomy.

Effects of remnant cholesterol on the efficacy of genotype-guided dual antiplatelet in loss-of -function carriers with minor stroke or transient ischaemic attack: a post-hoc analysis of the CHANCE-2 trial.

Background: The atherogenicity of remnant cholesterol (RC), a contributor to residual risk of cardiovascular events, has been underlined by recent guidelines. We aimed to evaluate the relationship between RC levels and the efficacy and safety of genotype-guided dual antiplatelet therapy in the CHANCE-2 trial.

Methods: This post-hoc study used data from the CHANCE-2 trial, which was a randomised, double-blind, placebo-controlled trial of 6412 patients (aged >40 years) enrolled from 202 hospitals in China, between Sept 23, 2019, and March 22, 2021, who carried loss-of-function alleles and had either an acute minor stroke or high-risk transient ischaemic attack (TIA), and could start treatment within 24 h of symptom onset.

Adipose tissue specific insulin resistance and prognosis of nondiabetic patients with ischemic stroke.

Background: Insulin resistance is linked to atherosclerotic cardiovascular diseases and stroke, whereas less is known about adipose tissue specific insulin resistance and outcomes after ischemic stroke. This study aimed to estimate the association between adipose tissue specific insulin resistance and prognosis of nondiabetic patients with ischemic stroke.

Methods: Patients with ischemic stroke without a history of diabetes mellitus in the Third China National Stroke Registry were included.

Ticagrelor Versus Clopidogrel in Minor Stroke or Transient Ischemic Attack With Intracranial Artery Stenosis: A Post Hoc Analysis of CHANCE-2.

Background This study aimed to investigate the efficacy and safety of ticagrelor-aspirin versus clopidogrel-aspirin in Chinese patients by the presence and clinical presentation of intracranial artery stenosis (ICAS) using randomized trial data from the CHANCE-2 (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events-II) trial. Methods and Results A total of 6412 patients with minor stroke or transient ischemic attack who carried loss-of-function alleles were randomized to either the ticagrelor-aspirin or clopidogrel-aspirin group. Patients without imaging of the intracranial artery were excluded from the nonprespecified subgroup analysis of CHANCE-2.