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.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.
5.Efficacy of Amitriptyline in Irritable Bowel Syndrome:A Systematic Review and Meta-analysis
Minahil IQBAL ; Sara HIRA ; Humza SAEED ; Sufyan SHAHID ; Suha T BUTT ; Kamran RASHID ; Mohammad AHMAD ; Hammad HUSSAIN ; Anzalna MUGHAL ; Gabriel P A COSTA ; Fernanda GUSHKEN ; Neil NERO ; Shreya SENGUPTA ; Akhil ANAND
Journal of Neurogastroenterology and Motility 2025;31(1):28-37
Background/Aims:
Amitriptyline is prescribed off-label for irritable bowel syndrome (IBS). We conducted a meta-analysis to assess its efficacy.
Methods:
A systematic literature review was conducted until November 10, 2023, using MEDLINE, Embase, Cochrane Library, and Web of Science to study the efficacy of amitriptyline in patients with IBS. We included all randomized controlled trials that compared amitriptyline to placebo. Revised Cochrane risk-of-bias tool was used to assess the quality of studies. Meta-analyses were performed using a bivariate random-effects model. Statistical analyses were performed using R Software 4.2.3 and heterogeneity was assessed with I 2 statistics.
Results:
Seven trials were included with 796 patients (61% female). Amitriptyline was associated with better treatment response (OR, 5.30; 95% CI, 2.47 to 11.39; P < 0.001), reduced Irritable Bowel Syndrome Symptom Severity Scores (MD, –50.72; 95% CI, –94.23 to –7.20; P = 0.020) and improved diarrhea (OR, 10.55; 95% CI, 2.90 to 38.41; P < 0.001). No significant difference between the 2 groups regarding the adverse effects was observed. Three trials showed an overall low risk of bias, 2 trials showed an overall high risk of bias due to randomization and missing data, and 2 trials had some concerns regarding missing data.
Conclusions
Amitriptyline was found to be well-tolerated and effective in treating IBS compared to placebo. These findings support the use of amitriptyline for the management of IBS, particularly among patients with the IBS diarrhea subtype. Future research should focus on the dose-dependent effects of amitriptyline in IBS to better guide clinicians in personalized titration regimens.
6.Efficacy of Amitriptyline in Irritable Bowel Syndrome:A Systematic Review and Meta-analysis
Minahil IQBAL ; Sara HIRA ; Humza SAEED ; Sufyan SHAHID ; Suha T BUTT ; Kamran RASHID ; Mohammad AHMAD ; Hammad HUSSAIN ; Anzalna MUGHAL ; Gabriel P A COSTA ; Fernanda GUSHKEN ; Neil NERO ; Shreya SENGUPTA ; Akhil ANAND
Journal of Neurogastroenterology and Motility 2025;31(1):28-37
Background/Aims:
Amitriptyline is prescribed off-label for irritable bowel syndrome (IBS). We conducted a meta-analysis to assess its efficacy.
Methods:
A systematic literature review was conducted until November 10, 2023, using MEDLINE, Embase, Cochrane Library, and Web of Science to study the efficacy of amitriptyline in patients with IBS. We included all randomized controlled trials that compared amitriptyline to placebo. Revised Cochrane risk-of-bias tool was used to assess the quality of studies. Meta-analyses were performed using a bivariate random-effects model. Statistical analyses were performed using R Software 4.2.3 and heterogeneity was assessed with I 2 statistics.
Results:
Seven trials were included with 796 patients (61% female). Amitriptyline was associated with better treatment response (OR, 5.30; 95% CI, 2.47 to 11.39; P < 0.001), reduced Irritable Bowel Syndrome Symptom Severity Scores (MD, –50.72; 95% CI, –94.23 to –7.20; P = 0.020) and improved diarrhea (OR, 10.55; 95% CI, 2.90 to 38.41; P < 0.001). No significant difference between the 2 groups regarding the adverse effects was observed. Three trials showed an overall low risk of bias, 2 trials showed an overall high risk of bias due to randomization and missing data, and 2 trials had some concerns regarding missing data.
Conclusions
Amitriptyline was found to be well-tolerated and effective in treating IBS compared to placebo. These findings support the use of amitriptyline for the management of IBS, particularly among patients with the IBS diarrhea subtype. Future research should focus on the dose-dependent effects of amitriptyline in IBS to better guide clinicians in personalized titration regimens.
7.Efficacy of Amitriptyline in Irritable Bowel Syndrome:A Systematic Review and Meta-analysis
Minahil IQBAL ; Sara HIRA ; Humza SAEED ; Sufyan SHAHID ; Suha T BUTT ; Kamran RASHID ; Mohammad AHMAD ; Hammad HUSSAIN ; Anzalna MUGHAL ; Gabriel P A COSTA ; Fernanda GUSHKEN ; Neil NERO ; Shreya SENGUPTA ; Akhil ANAND
Journal of Neurogastroenterology and Motility 2025;31(1):28-37
Background/Aims:
Amitriptyline is prescribed off-label for irritable bowel syndrome (IBS). We conducted a meta-analysis to assess its efficacy.
Methods:
A systematic literature review was conducted until November 10, 2023, using MEDLINE, Embase, Cochrane Library, and Web of Science to study the efficacy of amitriptyline in patients with IBS. We included all randomized controlled trials that compared amitriptyline to placebo. Revised Cochrane risk-of-bias tool was used to assess the quality of studies. Meta-analyses were performed using a bivariate random-effects model. Statistical analyses were performed using R Software 4.2.3 and heterogeneity was assessed with I 2 statistics.
Results:
Seven trials were included with 796 patients (61% female). Amitriptyline was associated with better treatment response (OR, 5.30; 95% CI, 2.47 to 11.39; P < 0.001), reduced Irritable Bowel Syndrome Symptom Severity Scores (MD, –50.72; 95% CI, –94.23 to –7.20; P = 0.020) and improved diarrhea (OR, 10.55; 95% CI, 2.90 to 38.41; P < 0.001). No significant difference between the 2 groups regarding the adverse effects was observed. Three trials showed an overall low risk of bias, 2 trials showed an overall high risk of bias due to randomization and missing data, and 2 trials had some concerns regarding missing data.
Conclusions
Amitriptyline was found to be well-tolerated and effective in treating IBS compared to placebo. These findings support the use of amitriptyline for the management of IBS, particularly among patients with the IBS diarrhea subtype. Future research should focus on the dose-dependent effects of amitriptyline in IBS to better guide clinicians in personalized titration regimens.