1.Tenecteplase Beyond 4.5 Hours in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis of Randomized Clinical Trials
Mohammad ALADAWI ; Mohammad T. ABUAWWAD ; Mohammad J. J. TAHA ; Yasmeena Abdelall KOZAA ; Warda A. ALRUBASY ; Abdullah HAMAD ; Fatema Ahmad ALHNIDI ; Mohamed ELFIL ; Zaid NAJDAWI ; Xiaohan PENG ; Felicia HATAWAY ; Ekaterina BAKRADZE ; Michael J. LYERLY
Journal of Stroke 2025;27(2):184-194
Background:
and Purpose Acute ischemic stroke (AIS) is a leading cause of disability worldwide. While intravenous thrombolysis is recommended within 4.5 hours of last known well (LKW) time, many patients present beyond this window.
Methods:
We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating tenecteplase (TNK) administration in AIS patients within 4.5 to 24 hours of LKW. The primary outcomes assessed functional independence and ordinal modified Rankin Scale (mRS) shift at 90 days. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and mortality at 90 days.
Results:
Three RCTs were included, comprising 1,054 patients (532 TNK and 522 standard medical therapy) with a mean age of 69 years, 59% males, and median baseline National Institutes of Health Stroke Scale score of 10.5. TNK treatment was associated with mRS 0–2 at 90 days (odds ratio [OR]: 1.33, 95% confidence interval [CI]: 1.04–1.70, P=0.023), indicating a 33% higher likelihood of achieving functional independence. However, the ordinal mRS shift showed no significant difference (standardized mean difference: 0.01, 95% CI: -0.37–0.39, P=0.09). Safety outcomes indicated no difference in the rates of sICH (OR: 2.07, 95% CI: 0.86–5.00, P=0.1), and no difference in 90-day mortality (OR: 1.08, 95% CI: 0.76–1.53, P=0.67).
Conclusion
This meta-analysis suggests TNK might be safe and effective for selected AIS patients in the 4.5- to 24-hour time window, offering improved functional outcomes without a significant increase in hemorrhagic complications.
2.Tenecteplase Beyond 4.5 Hours in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis of Randomized Clinical Trials
Mohammad ALADAWI ; Mohammad T. ABUAWWAD ; Mohammad J. J. TAHA ; Yasmeena Abdelall KOZAA ; Warda A. ALRUBASY ; Abdullah HAMAD ; Fatema Ahmad ALHNIDI ; Mohamed ELFIL ; Zaid NAJDAWI ; Xiaohan PENG ; Felicia HATAWAY ; Ekaterina BAKRADZE ; Michael J. LYERLY
Journal of Stroke 2025;27(2):184-194
Background:
and Purpose Acute ischemic stroke (AIS) is a leading cause of disability worldwide. While intravenous thrombolysis is recommended within 4.5 hours of last known well (LKW) time, many patients present beyond this window.
Methods:
We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating tenecteplase (TNK) administration in AIS patients within 4.5 to 24 hours of LKW. The primary outcomes assessed functional independence and ordinal modified Rankin Scale (mRS) shift at 90 days. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and mortality at 90 days.
Results:
Three RCTs were included, comprising 1,054 patients (532 TNK and 522 standard medical therapy) with a mean age of 69 years, 59% males, and median baseline National Institutes of Health Stroke Scale score of 10.5. TNK treatment was associated with mRS 0–2 at 90 days (odds ratio [OR]: 1.33, 95% confidence interval [CI]: 1.04–1.70, P=0.023), indicating a 33% higher likelihood of achieving functional independence. However, the ordinal mRS shift showed no significant difference (standardized mean difference: 0.01, 95% CI: -0.37–0.39, P=0.09). Safety outcomes indicated no difference in the rates of sICH (OR: 2.07, 95% CI: 0.86–5.00, P=0.1), and no difference in 90-day mortality (OR: 1.08, 95% CI: 0.76–1.53, P=0.67).
Conclusion
This meta-analysis suggests TNK might be safe and effective for selected AIS patients in the 4.5- to 24-hour time window, offering improved functional outcomes without a significant increase in hemorrhagic complications.
3.Tenecteplase Beyond 4.5 Hours in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis of Randomized Clinical Trials
Mohammad ALADAWI ; Mohammad T. ABUAWWAD ; Mohammad J. J. TAHA ; Yasmeena Abdelall KOZAA ; Warda A. ALRUBASY ; Abdullah HAMAD ; Fatema Ahmad ALHNIDI ; Mohamed ELFIL ; Zaid NAJDAWI ; Xiaohan PENG ; Felicia HATAWAY ; Ekaterina BAKRADZE ; Michael J. LYERLY
Journal of Stroke 2025;27(2):184-194
Background:
and Purpose Acute ischemic stroke (AIS) is a leading cause of disability worldwide. While intravenous thrombolysis is recommended within 4.5 hours of last known well (LKW) time, many patients present beyond this window.
Methods:
We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating tenecteplase (TNK) administration in AIS patients within 4.5 to 24 hours of LKW. The primary outcomes assessed functional independence and ordinal modified Rankin Scale (mRS) shift at 90 days. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and mortality at 90 days.
Results:
Three RCTs were included, comprising 1,054 patients (532 TNK and 522 standard medical therapy) with a mean age of 69 years, 59% males, and median baseline National Institutes of Health Stroke Scale score of 10.5. TNK treatment was associated with mRS 0–2 at 90 days (odds ratio [OR]: 1.33, 95% confidence interval [CI]: 1.04–1.70, P=0.023), indicating a 33% higher likelihood of achieving functional independence. However, the ordinal mRS shift showed no significant difference (standardized mean difference: 0.01, 95% CI: -0.37–0.39, P=0.09). Safety outcomes indicated no difference in the rates of sICH (OR: 2.07, 95% CI: 0.86–5.00, P=0.1), and no difference in 90-day mortality (OR: 1.08, 95% CI: 0.76–1.53, P=0.67).
Conclusion
This meta-analysis suggests TNK might be safe and effective for selected AIS patients in the 4.5- to 24-hour time window, offering improved functional outcomes without a significant increase in hemorrhagic complications.
4.Endovascular Thrombectomy for Large Ischemic Strokes: A Living Systematic Review and Meta-Analysis of Randomized Trials
Rami Z. MORSI ; Mohamed ELFIL ; Hazem S. GHAITH ; Mohammad ALADAWI ; Ahmad ELMASHAD ; Sachin KOTHARI ; Harsh DESAI ; Shyam PRABHAKARAN ; Fawaz AL-MUFTI ; Tareq KASS-HOUT
Journal of Stroke 2023;25(2):214-222
Background:
and Purpose New studies have shown that endovascular thrombectomy (EVT) is safe and effective for acute ischemic stroke (AIS) patients with large ischemic areas. The aim of our study is to conduct a living systematic review and meta-analysis of randomized trials comparing EVT versus medical management only.
Methods:
We searched MEDLINE, Embase, and the Cochrane Library to identify randomized controlled trials (RCTs) comparing EVT versus medical management alone in AIS patients with large ischemic regions. We conducted our meta-analysis using fixed-effect models to compare functional independence, mortality, and symptomatic intracranial hemorrhage (sICH) between EVT and standard medical management only. We assessed the risk of bias using the Cochrane risk-of-bias tool and the certainty of evidence for each outcome using the Grading of Recommendations, Assessment, Development, and Evaluations approach.
Results:
Of 14,513 citations, we included 3 RCTs with a total of 1,010 participants. We found low-certainty evidence of possibly a large increase in the proportion of patients with functional independence (risk difference [RD] 30.3%, 95% CI 15.0% to 52.3%), low-certainty evidence of possibly a small non-significant decrease in mortality (RD -0.7%, 95% CI -3.8% to 3.5%), and low-certainty evidence of possibly a small non-significant increase in sICH (RD 3.1%, 95% CI -0.3% to 9.8%) for AIS patients with large infarcts who underwent EVT compared to medical management only.
Conclusion
Low-certainty evidence shows that there is possibly a large increase in functional independence, a small non-significant decrease in mortality, and a small non-significant increase in sICH amongst AIS patients with large infarcts undergoing EVT compared to medical management only.