Safety and efficacy of low-cost alternative urokinase in acute ischemic stroke: A systematic review and meta-analysis

Introduction: Use of intravenous thrombolysis (IVT) for treatment of acute ischemic stroke (AIS) varies greatly between countries, ranging from 10% to 15% in high-income countries to less than 2% in low-and middle in-come countries (LMICs). This is because alteplase is expensive and has been cited as one of the most common barriers to IVT in LMICs. Urokinase (UK) is a thrombolytic agent which is almost 50 times cheaper with easier production and purification than alteplase. UK may become a cost-effective option for IVT in LMICs if it is found to be safe and effective. We conducted this study to assess the existing evidence on the safety and efficacy of UK vs alteplase for IVT in AIS.Methods: The study was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and meta-Analyses) guideline. Systematic literature search was done in PubMed, EMBASE, and Google Scholar for English literature published from 2010 to 2021.Results: A total of 4061 participants in the alteplase and 2062 participants in the UK group were included in the final statistical analysis. After IVT, a good functional outcome at last follow-up was found among 80.57 % of patients in the alteplase group compared to 73.79 % of patients in the UK group (OR: 1.11; 95 % CI: 0.95- 1.31; I2 = 0 %; P = 0.18). Symptomatic Intracerebral Hemorrhage (sICH) was found among 1.77 % of patients in the alteplase group compared to 2.83 % of patients in the UK group (OR: 0.84; 95 % CI: 0.56- 1.26; I2 = 0 %; P = 0.41). Similarly, mortality was found among 5.03 % of patients in the alteplase group compared to 5.42 % of patients in the UK group (OR: 0.87; 95 % CI: 0.66-1.14; I2 = 0 %; P = 0.30).Conclusion: Our meta-analysis found that intravenous UK is not inferior to alteplase in terms of safety and efficacy and can be a viable alternative for IVT in AIS patients in LMICs.