A new thrombolytic drug for acute ischaemic stroke

Abstract

Almost 100 years have passed since substances derived from bacteria (streptokinase and staphylokinase), urine (urokinase), or bat saliva (desmoteplase) were shown to activate the fibrinolytic system, suggesting their potential to treat arterial thrombosis. Studies with streptokinase in patients with acute ischaemic stroke in the 1960s, before the advent of CT, showed an increased risk of intracranial haemorrhage and an absence of overall efficacy. 1 Röther J Ford GA Thijs VN Thrombolytics in acute ischaemic stroke: historical perspective and future opportunities. Cerebrovasc Dis. 2013; 35: 313-319 Crossref PubMed Scopus (36) Google Scholar The fairly low fibrin specificity of streptokinase stimulated research to find substances with a better risk–benefit profile. In 1979, tissue plasminogen activator was purified, and recombinant tissue plasminogen activator (rtPA) was developed in 1983, leading to clinical trials in which the superiority of rtPA versus streptokinase was shown in patients with acute myocardial infarction. 1 Röther J Ford GA Thijs VN Thrombolytics in acute ischaemic stroke: historical perspective and future opportunities. Cerebrovasc Dis. 2013; 35: 313-319 Crossref PubMed Scopus (36) Google Scholar In 1995, a pivotal trial from the National Institute of Neurological Disorders and Stroke showed that the benefits of rtPA (alteplase) outweighed the risks in treatment of patients with acute ischaemic stroke. 2 National Institute of Neurological DisordersStroke rt-PA Stroke Study GroupTissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995; 333: 1581-1587 Crossref PubMed Scopus (9747) Google Scholar Despite this success, alteplase has somewhat low recanalisation rates and an increased risk of bleeding. Other thrombolytic drugs still under investigation include tenecteplase, which has a higher fibrin specificity than alteplase, and desmoteplase, which is a fibrin-specific recombinant plasminogen activator. Non-immunogenic recombinant staphylokinase versus alteplase for patients with acute ischaemic stroke 4·5 h after symptom onset in Russia (FRIDA): a randomised, open label, multicentre, parallel-group, non-inferiority trialNon-immunogenic staphylokinase was non-inferior to alteplase for patients with acute ischaemic stroke. Mortality, symptomatic intracranial haemorrhage, and serious adverse events did not differ significantly between groups. Future studies are needed to continue to assess the safety and efficacy of non-immunogenic staphylokinase in patients with acute ischaemic stroke within the 4·5 h time window, and to assess the drug in patients with acute ischaemic stroke outside this time window with reperfusion CT or magnetic resonance angiography followed by thrombectomy if necessary. Full-Text PDF Correction to Lancet Neurol 2021; 20: 687–89Rothwell PM, Buchan AM. A new thrombolytic drug for acute ischaemic stroke. Lancet Neurol 2021; 20: 687–89—In this Comment, the spelling of non-immunogenic has been corrected throughout. This correction has been made to the online version as of Aug 27, 2021. Full-Text PDF