ImportancePrevious studies suggested a benefit of argatroban plus alteplase (recombinant tissue-type plasminogen activator) in patients with acute ischemic stroke (AIS). However, robust evidence in trials with large sample sizes is lacking.ObjectiveTo assess the efficacy of argatroban plus alteplase for AIS.Design, Setting, and ParticipantsThis multicenter, open-label, blinded end point randomized clinical trial including 808 patients with AIS was conducted at 50 hospitals in China with enrollment from January 18, 2019, through October 30, 2021, and final follow-up on January 24, 2022.InterventionsEligible patients were randomly assigned within 4.5 hours of symptom onset to the argatroban plus alteplase group (n = 402), which received intravenous argatroban (100 μg/kg bolus over 3-5 minutes followed by an infusion of 1.0 μg/kg per minute for 48 hours) within 1 hour after alteplase (0.9 mg/kg; maximum dose, 90 mg; 10% administered as 1-minute bolus, remaining infused over 1 hour), or alteplase alone group (n = 415), which received intravenous alteplase alone. Both groups received guideline-based treatments.Main Outcomes and MeasuresThe primary end point was excellent functional outcome, defined as a modified Rankin Scale score (range, 0 [no symptoms] to 6 [death]) of 0 to 1 at 90 days. All end points had blinded assessment and were analyzed on a full analysis set.ResultsAmong 817 eligible patients with AIS who were randomized (median [IQR] age, 65 [57-71] years; 238 [29.1%] women; median [IQR] National Institutes of Health Stroke Scale score, 9 [7-12]), 760 (93.0%) completed the trial. At 90 days, 210 of 329 participants (63.8%) in the argatroban plus alteplase group vs 238 of 367 (64.9%) in the alteplase alone group had an excellent functional outcome (risk difference, −1.0% [95% CI, −8.1% to 6.1%]; risk ratio, 0.98 [95% CI, 0.88-1.10]; P = .78). The percentages of participants with symptomatic intracranial hemorrhage, parenchymal hematoma type 2, and major systemic bleeding were 2.1% (8/383), 2.3% (9/383), and 0.3% (1/383), respectively, in the argatroban plus alteplase group and 1.8% (7/397), 2.5% (10/397), and 0.5% (2/397), respectively, in the alteplase alone group.Conclusions and RelevanceAmong patients with acute ischemic stroke, treatment with argatroban plus intravenous alteplase compared with alteplase alone did not result in a significantly greater likelihood of excellent functional outcome at 90 days.Trial RegistrationClinicalTrials.gov Identifier: NCT03740958

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Objective To investigate an association between percentage lipid‐rich necrotic core (LRNC) and an index ischemic stroke in an embolic stroke of undetermined source (ESUS) cohort. Methods A total of 167 ESUS patients with 259 non‐stenotic intracranial plaques including 155 ipsilateral and 104 contralateral to stroke were finally enrolled in the current analysis. The multi‐dimensional parameters involving remodeling index (RI), plaque burden (PB), LRNC, discontinuity of plaque surface (DPS), intraplaque hemorrhage (IPH), and vulnerable plaque defined as presence of complicated plaque were evaluated by high‐resolution magnetic resonance imaging. Results We found that %LRNC was an independent predictor for ESUS in model 1 (OR: 2.574, 95% CI: 1.854–3.573, P < 0.001), and model 2 (OR: 2.550, 95% CI: 1.835–3.545, P < 0.001), but the association was not seen in PB. In receiver operating characteristic curve analysis, the discrimination of LRNC for ESUS was significantly superior to that of PB (absolute difference: 0.121, 95% CI: 0.056–0.205, P < 0.001). Importantly, a significantly positive synergy between the remodeling pattern and LRNC in response to plaque vulnerability was found by Sankey diagram (P for interaction = 0.001). Conclusion This is the first report that LRNC, beyond PB, may be correlated with an index ESUS, and a synergistic effect between positive remodeling and larger LRNC could promote plaque vulnerability. The findings suggest that a potential target subgroup may benefit from stroke prevention with intensive statin, although this must be confirmed in future.

Aim To investigate whether diabetes and fasting blood glucose (FBG) levels affect the efficacy of remote ischaemic conditioning (RIC) using the database included in the Remote Ischaemic Conditioning for Acute Moderate Ischaemic Stroke (RICAMIS) trial. Methods A total of 1707 patients were enrolled in this post hoc study, including 535 patients with diabetes and 1172 without diabetes. Each group was further divided into RIC and control subgroups. The primary outcome was excellent functional outcome, defined as a modified Rankin Scale (mRS) score of 0 to 1 at 90 days. The difference in the proportion of patients with excellent functional outcome between the RIC subgroup and control subgroup was compared in diabetic and non‐diabetic patients, respectively, and the interactions of treatment assignment with diabetes status and FBG were evaluated. Results Compared with the control group, RIC produced a significantly higher proportion of patients with excellent functional outcome in the non‐diabetic group (70.5% vs. 63.2%; odds ratio [OR] 1.487, 95% confidence interval [CI] 1.134‐1.949; P = 0.004), while a similar, but not significant difference was observed in the diabetic group (65.3% vs. 59.8%; OR 1.424, 95% CI 0.978‐2.073; P = 0.065). Similar results were observed in patients with normal FBG levels (69.3% vs. 63.7%; OR 1.363, 95% CI 1.011‐1.836; P = 0.042) and those with high FBG levels (64.2% vs. 58%; OR 1.550, 95% CI 1.070‐2.246; P = 0.02). Furthermore, we did not find an interaction effect of intervention (RIC or control) by different diabetes status or FBG levels on clinical outcomes (P > 0.05 for all). However, diabetes (OR 0.741, 95% CI 0.585‐0.938; P = 0.013) and high FBG (OR 0.715, 95% CI 0.553‐0.925; P = 0.011) were independently associated with functional outcomes in patients overall. Conclusion Diabetes and FBG levels did not influence the neuroprotective effect of RIC in acute moderate ischaemic stroke, although diabetes and high FBG levels were independently associated with functional outcomes.

Nitric oxide (NO) is an important messenger molecule and effector molecule. This study aimed to investigate the relation of neuronal nitric oxide synthase (nNOS) gene polymorphism with ischemic stroke in Han Chinese of North China. This was a case-control study. A total of 413 patients with ischemic stroke were recruited from Han Chinese of North China. There were 201 males and 212 females. In addition, 477 healthy subjects served as controls including 224 males and 253 females. Multiplex SNaPshot was employed to detect nNOS gene polymorphism (rs2293050, rs2139733, rs7308402, and rs1483757). Results showed that the rs1483757, rs2139733, and rs2293050 genotypes and allele frequencies were comparable between patients and controls. However, ischemic stroke patients had significantly reduced AG genotype and A allele frequency when compared with controls (P = 0.037, P = 0.041). After adjusting confounding factors (gender, age, smoking, history of drinking, hypertension, and diabetes), AG genotype and A allele were still related to ischemic stroke (OR = 0.572, 95% CI: 0.335–0.978, P = 0.041; OR = 0.611, 95% C: 0.378–0.985, and P = 0.041) and both were found to be protective factors. Our results showed that rs7308402 gene polymorphism of nNOS is related to ischemic stroke in Han Chinese of North China.