Objective:To systematically evaluate the efficacy and safety of intravenous thrombolysis with tenecteplase (TNK) in acute ischemic stroke (AIS) across different time windows.Methods:Randomized controlled trials investigating TNK in AIS were retrieved from PubMed, Embase, Web of Science, Cochrane Library, CNKI, and Wanfang databases, with data collected up to May 2025. Experimental group received intravenous thrombolysis with 0.25 mg/kg TNK, either alone or in combination with mechanical thrombectomy (MT). Control group received alteplase, placebo, standard medication (containing butylphthalide), MT, or above-mentioned drugs combined with MT. These patients were within 4.5 hours of onset (within-time window) or within 4.5-24 hours of onset (extended-time window). Efficacy indexes included functional outcome excellent rate (modified Rankin scale [mRS] score of 0-1 at 3 months after treatment), early neurological improvement rate (National Institutes of Health Stroke Scale [NIHSS] score improvement≥4 or NIHSS score ranged 0-1 within 72 of treatment), and recanalization rate 24 h after treatment. Safety indexes comprised symptomatic intracranial hemorrhage (sICH) rate within 48 h of treatment, and mortality rate and rate of serious adverse events (SAEs) within 90 d of treatment. Quality of the trials was assessed according to Cochrane handbook for systematic reviews of interventions (version 5.1). Meta-analysis was conducted using Stata software, with pooling data as risk difference ( RD). Results:Sixteen articles (11 were within-time window ones, and 5 were extended-time window ones), involving 9,430 AIS patients, were included. Quality grade of these articles is B-level. (1) In articles of within-time window: the experimental group had a significantly higher functional outcome excellent rate compared with the control group ( RD=0.031, 95% CI: 0.009-0.052, P=0.005); no significant difference was observed in early neurological improvement rate ( RD=0.016, 95% CI: -0.012-0.043, P=0.260), recanalization rate ( RD=0.040, 95% CI: 0.000-0.081, P=0.053), sICH rate ( RD=0.005, 95% CI: -0.002-0.012, P=0.198), mortality rate ( RD=0.000, 95% CI: -0.012-0.013, P=0.950), or SAE rate ( RD=0.003, 95% CI: -0.028-0.033, P=0.870) between the two groups. (2) In articles of extended-time window: the experimental group exhibited significantly higher functional outcome excellent rate ( RD=0.064, 95% CI: 0.016-0.113, P=0.009), early neurological improvement rate ( RD=0.101, 95% CI: 0.023-0.180, P=0.012), and recanalization rate ( RD=0.131, 95% CI: 0.059-0.203, P<0.001) compared with the control group; no significant difference was found in sICH rate ( RD=0.014, 95% CI: -0.003-0.032, P=0.097), mortality rate ( RD=0.006, 95% CI: -0.030-0.041, P=0.752), or SAE rate ( RD=0.030, 95% CI: -0.037-0.097, P=0.385) between the two groups. Conclusion:Intravenous thrombolysis with TNK is safe and effective in AIS patients at both within-time window and extended-time window.

Objective:To systematically evaluate the efficacy and safety of intravenous thrombolysis with tenecteplase (TNK) in acute ischemic stroke (AIS) across different time windows.Methods:Randomized controlled trials investigating TNK in AIS were retrieved from PubMed, Embase, Web of Science, Cochrane Library, CNKI, and Wanfang databases, with data collected up to May 2025. Experimental group received intravenous thrombolysis with 0.25 mg/kg TNK, either alone or in combination with mechanical thrombectomy (MT). Control group received alteplase, placebo, standard medication (containing butylphthalide), MT, or above-mentioned drugs combined with MT. These patients were within 4.5 hours of onset (within-time window) or within 4.5-24 hours of onset (extended-time window). Efficacy indexes included functional outcome excellent rate (modified Rankin scale [mRS] score of 0-1 at 3 months after treatment), early neurological improvement rate (National Institutes of Health Stroke Scale [NIHSS] score improvement≥4 or NIHSS score ranged 0-1 within 72 of treatment), and recanalization rate 24 h after treatment. Safety indexes comprised symptomatic intracranial hemorrhage (sICH) rate within 48 h of treatment, and mortality rate and rate of serious adverse events (SAEs) within 90 d of treatment. Quality of the trials was assessed according to Cochrane handbook for systematic reviews of interventions (version 5.1). Meta-analysis was conducted using Stata software, with pooling data as risk difference ( RD). Results:Sixteen articles (11 were within-time window ones, and 5 were extended-time window ones), involving 9,430 AIS patients, were included. Quality grade of these articles is B-level. (1) In articles of within-time window: the experimental group had a significantly higher functional outcome excellent rate compared with the control group ( RD=0.031, 95% CI: 0.009-0.052, P=0.005); no significant difference was observed in early neurological improvement rate ( RD=0.016, 95% CI: -0.012-0.043, P=0.260), recanalization rate ( RD=0.040, 95% CI: 0.000-0.081, P=0.053), sICH rate ( RD=0.005, 95% CI: -0.002-0.012, P=0.198), mortality rate ( RD=0.000, 95% CI: -0.012-0.013, P=0.950), or SAE rate ( RD=0.003, 95% CI: -0.028-0.033, P=0.870) between the two groups. (2) In articles of extended-time window: the experimental group exhibited significantly higher functional outcome excellent rate ( RD=0.064, 95% CI: 0.016-0.113, P=0.009), early neurological improvement rate ( RD=0.101, 95% CI: 0.023-0.180, P=0.012), and recanalization rate ( RD=0.131, 95% CI: 0.059-0.203, P<0.001) compared with the control group; no significant difference was found in sICH rate ( RD=0.014, 95% CI: -0.003-0.032, P=0.097), mortality rate ( RD=0.006, 95% CI: -0.030-0.041, P=0.752), or SAE rate ( RD=0.030, 95% CI: -0.037-0.097, P=0.385) between the two groups. Conclusion:Intravenous thrombolysis with TNK is safe and effective in AIS patients at both within-time window and extended-time window.

Objective:To examine the prevention effecacy and safety of preprotein convertase subtilisin-kexin 9 (PCSK9) inhibitors in stroke in patients with atherosclerotic cardiovascular disease (ASCVD) at primary and secondary prevention.Methods:PubMed, Embase, Web of Science, Cochrane Library, and Wanfang and CNKI databases were searched for randomized controlled trials comparing evolocumab, alirocumab, tafolecimab or inclisiran (experimental group) with placebo or conventional therapy (control group) in hyperlipidemia and ASCVD from inception to March 2024. Valid data were extracted after screening and applying Cochrane Literature quality assessment tool to assess the literature quality. Efficacy outcome (incidences of stroke and ischemic stroke) and safety outcome (cardiovascular mortality, and incidences of aminotransferase increased by more than 3 times, creatine kinase increased by more than 3 times, allergic reaction and hemorrhagic stroke) were recorded. Meta analysis of the extracted data was conducted using Stata software to calculate the risk difference ( RD). Results:Twenty articles (21 randomized controlled trials) were included with 62 799 patients. For primary prevention, no significant difference was found between PCSK9 inhibitors and control groups in stroke incidence ( RD=0.000, 95% CI: -0.002-0.003, P=0.905) or ischemic stroke incidence ( RD=0.001, 95% CI: -0.005-0.006, P=0.824); incidence of creatine kinase increased by more than 3 times in the PCSK9 inhibitors group was significantly decreased compared with that in the control group ( RD=-0.005, 95% CI: -0.010-0.000, P=0.039). For secondary prevention, PCSK9 inhibitors group had significantly reduced stroke incidence ( RD=-0.004, 95% CI: -0.006--0.002, P<0.001) and ischemic stroke incidence ( RD=-0.003, 95% CI: -0.005--0.002, P<0.001) compared with control group; no significant differences in cardiovascular mortality, or incidences of aminotransferase increased by more than 3 times, creatine kinase increased by more than 3 times, allergic reaction and hemorrhagic stroke were noted between the PCSK9 inhibitors group and control group ( P>0.05). Conclusion:PCSK9 inhibitors in primary prevention have no significant effect on stroke or ischemic stroke incidences, but can decrease the incidence of creatine kinase increased by more than 3 times; PCSK9 inhibitors in secondary prevention can reduce stroke and ischemic stroke incidences without increasing complications and thus enjoying certain safety.

Objective:To evaluate the preventive role and safety of evolocumab and alirocumab in ischemic stroke in hyperlipidemia and atherosclerotic high-risk cardiovascular patients.Methods:PubMed, Embase, Web of Science, Cochrane Library, Wanfang, and CNKI databases were searched for randomized controlled trials (RCTs) comparing evolocumab or alirocumab (experimental group) with placebo or usual care (control group) in hyperlipidemia and atherosclerotic high-risk cardiovascular patients from database inception to March 2023. References were screened and data were extracted according to the preset inclusion and exclusion criteria; incidence of ischemic stroke was as the efficacy index, and incidences of cardiovascular death, cognitive impairment, aminotransferase increased for more than 3 times and creatine kinase increased for more than 3 times were as the safety index. Cochrane Reviewer Handbook 2.0 was used to evaluate the RCTs literature quality. Meta analysis was performed using Stata software.Results:A total of 11 articles were included, including 12 studies with a total of 53 666 patients. Compared with the control group, the incidence of ischemic stroke in the experimental group was significantly decreased (risk difference [ RD]=-0.004, 95% CI: -0.005--0.002, P<0.001); there were no significant differences in the incidence of cardiovascular death, cognitive impairment, aminotransferase increased for more than 3 times and creatine kinase increased for more than 3 times between the 2 groups ( RD=-0.001, 95% CI: -0.004-0.001, P=0.401; RD=0.000, 95% CI: -0.003-0.002, P=0.638; RD=-0.001, 95% CI: -0.004-0.002, P=0.443; RD=-0.001, 95% CI: -0.003-0.000, P=0.137). Subgroup analysis was performed according to drugs: compared with the control group, the incidence of ischemic stroke was significantly reduced in the evolocumab group and alirocumab group ( RD=-0.004, 95% CI: -0.007--0.001, P=0.006; RD= -0.003, 95% CI: -0.006-0.000, P=0.024); there were no significant differences in incidences of cardiovascular death ( RD=0.001, 95% CI: -0.002-0.004, P=0.619; RD=-0.003, 95% CI: -0.007-0.001, P=0.100), cognitive impairment ( RD=0.001, 95% CI:-0.002-0.004, P=0.463; RD=-0.002, 95% CI: -0.005-0.001, P=0.145), aminotransferase increased for more than 3 times ( RD=0.000, 95% CI: -0.003-0.003, P=0.888; RD=-0.002, 95% CI: -0.007-0.003, P=0.392) or creatine kinase increased for more than 3 times ( RD=0.000, 95% CI: -0.002-0.002, P=0.668; RD=-0.002, 95% CI: -0.005-0.000, P=0.106) between the evolocumab group and alirocumab group. Subgroup analysis was performed according to the medication duration: compared with the control group, no significant differences in incidences of cardiovascular death ( RD=0.000, 95% CI:-0.022-0.022, P=1.000; RD=-0.003, 95% CI: -0.009-0.002, P=0.193; RD=-0.001, 95% CI:-0.004-0.002, P=0.521), cognitive impairment ( RD=-0.003, 95% CI: -0.014-0.008, P=0.569; RD=-0.001, 95% CI: -0.006-0.004, P=0.696; RD=0.000, 95% CI: -0.003-0.002, P=0.735), aminotransferase increased for more than 3 times ( RD=-0.002, 95% CI: -0.016-0.012, P=0.749; RD=-0.002, 95% CI: -0.013-0.010, P=0.773; RD=-0.001, 95% CI: -0.004-0.002, P=0.489) or creatine kinase increased for more than three times ( RD=-0.015, 95% CI: -0.032-0.003, P=0.099; RD= -0.011, 95% CI: -0.025-0.002, P=0.104; RD=0.000, 95% CI: -0.002-0.001, P=0.722) were noted among medication duration<1 year group, medication duration of 1-2 years group and medication duration>2 years group. Conclusion:Both evolocumab and alirocumab can reduce the incidence of ischemic stroke in hyperlipidemia and atherosclerotic high-risk cardiovascular patients, with good safety.