Efficacy and Safety of Fibrinolytics in Patients with Acute Ischaemic Stroke and Transient Ischaemic Attack: A Network Meta-Analysis of Randomized Controlled Trials
Aisha Rizwan Ahmed1, Aishwarya Koppanatham2, Mrinal Murali Krishna3, Meghna Joseph3, Issa Salha4, Rabbia Jabbar5, Rafael Reis de Oliveira6, Sana Ahmed6, Mir Wajid Majeed7, Jovana Ristic8, Gokul Rajith9, Zeeshan Mansuri10, Maryam Rizwan11, Lubna Al-Sharif12, Natalia Arturo Restrepo13, Paweł Chochoł14, Thomas Varkey15
1Jinnah Medical and Dental College, Karachi, SINDH, 2Andhra Medical College, 3Government Medical College Thiruvananthapuram, 4Trinity Centre for Global Health - Trinity College Dublin, 5Fatima memorial hospital FMHCMD, 6Federal University of Pará, Pará, Brazil, 7Government medical college Srinagar, India, 8Medical Faculty University of Belgrade, Serbia;, 9All India Institute of Medical Sciences, Guwahati, 10Gujarat Cancer Society Medical College, Ahmedabad, 11Baqai Medical College, Karachi, SINDH, 12An-Nahah national University, 13Universidad CES, Medellin, Antioquia, 14University of Warmia and Mazury in Olsztyn, Olsztyn, 15Banner University Medical Center
Objective:
Our Frequentist network meta-analysis (NMA) aims to explore the efficacy and safety outcomes of various fibrinolytic regimens in managing acute ischaemic stroke (AIS) and transient ischaemic attack (TIA) patients.
Background:
Intravenous thrombolysis with an alteplase bolus followed by infusion is the global standard of care for patients with AIS and TIA. However, emerging fibrinolytics have shown promising potential in terms of efficacy and safety, though it remains unclear which is superior for treating AIS and TIA
Design/Methods:
A comprehensive search of PubMed, Embase, and Cochrane databases was conducted to identify randomized controlled trials (RCTs) comparing various fibrinolytic regimens in patients with AIS and TIA, assessing the risk of 30-day and 90-day mortality, intracranial hemorrhage (ICH), and early neurological improvement (ENI).
Results:
A total of 30 RCTs were included with 15,695 patients. There was a statistically significant ENI in patients who underwent thrombolysis with tenecteplase compared with alteplase (RR 1.20; 95% CI 1.04-1.41) and no thrombolytic therapy (RR 1.33; 95% CI 1.02-1.75). There was no significant difference in risk of ICH, or mortality at 30 days and 90 days across any of the network comparisons between the various fibrinolytics. P-score analysis showed that tenecteplase had the highest probability of being the best strategy for ENI (p-score=0.94), followed by reteplase and alteplase. No fibrinolytic therapy was associated with the lowest probability of mortality at 90 days, followed by alteplase and tenecteplase.
Conclusions:
Among patients with AIS and TIA, tenecteplase demonstrates superior efficacy in achieving ENI when compared with alteplase and no fibrinolytic therapy. It also has the highest probability of being the most effective strategy for providing ENI compared with other fibrinolytics. Moreover, the risk of ICH and mortality is comparable across all fibrinolytic agents.
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