Current Drug Treatment of Acute Ischemic Stroke: Challenges and Opportunities
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Patient-level health outcomes for acute ischemic stroke have significantly improved in the last decade primarily because of superior overall case management, availability of tailored drug interventions, and advances in endovascular procedures. Nevertheless, disease registries show a “quality gap” across social determinants of health and between in-hospital and community-onset strokes. Several factors, including financing and infrastructure constraints, limited expertise, and clinical uncertainty, still prevent adherence to evidence-based clinical guidelines and optimal care pathways. This paper critically appraises existing evidence on the use of drug therapies in acute ischemic stroke, in an attempt to resolve physician-related subjective barriers for effective acute management of the disease. We conclude that intravenous administration of rt-PA (recombinant tissue-type plasminogen activator, alteplase) is an essential component of acute-phase pharmacologic treatment and a driver for the improvement of overall ischemic stroke health outcomes. The safety profile of alteplase and similar treatments are well within the patient benefit zone of eligible patients when compared to non-treatment alternatives. Monomodal neuroprotective drugs with single or pleiotropic mechanisms of action have failed to support long-term sustainable results. Drugs with complex mechanisms of action that promote neurorecovery, such as cerebrolysin, are valid options for adjunctive treatment of acute ischemic stroke. Recent years have shown clear improvements in the methodology and design of clinical trials, with an increase in overall internal and external validity. A better understanding of study limitations has not hindered, but enhanced their potential to contribute, together with sometimes superior data sources, to health decision making.
Compliance with Ethical Standards
No funding was received for the preparation of this article.
Conflict of Interest
Dafin Muresanu has served as the coordinating investigator of the academic trial Cerebrolysin and Recovery After Stroke (CARS). Adina Stan has served as the principal investigator in the academic trials Cerebrolysin and early neurorehabilitation in patients with acute ischemic stroke and Cerebrolysin REGistry Study in Stroke - a High-quality Observational Study of Comparative Effectiveness (C-REGS 2). Stefan Strilciuc has no conflicts of interest that are directly relevant to the contents of this article.
- 8.Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, et al. 2018 guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2018;49(3):e46–99.CrossRefGoogle Scholar
- 9.US FDA. Drug approval package: Alteplase. https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/alteplase_toc.cfm. Accessed 19 Aug 2019.
- 12.Emberson J, Lees KR, Lyden P, Blackwell L, Albers G, Bluhmki E, et al. Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials. Lancet Lond Engl. 2014;384(9958):1929–35.CrossRefGoogle Scholar
- 27.Anderson CS, Huang Y, Lindley RI, Chen X, Arima H, Chen G, et al. Intensive blood pressure reduction with intravenous thrombolysis therapy for acute ischaemic stroke (ENCHANTED): an international, randomised, open-label, blinded-endpoint, phase 3 trial. Lancet. 2019;393(10174):877–88.CrossRefGoogle Scholar
- 34.Churilov L, Ma H, Campbell BC, Davis SM, Donnan GA. Statistical analysis plan for EXtending the time for Thrombolysis in Emergency Neurological Deficits (EXTEND) trial. Int J Stroke. 2018;7:1747493018816101.Google Scholar
- 42.Muresanu D. Neurotrophic factors. Cluj-Napoca: Libripress; 2003.Google Scholar
- 43.Stan A, Birle C, Blesneag A, Iancu M. Cerebrolysin and early neurorehabilitation in patients with acute ischemic stroke: a prospective, randomized, placebo-controlled clinical study. J Med Life. 2017;10(4):216–22.Google Scholar
- 46.Ziganshina LE, Abakumova T, Vernay L. Cerebrolysin for acute ischaemic stroke. Cochrane Database Syst Rev. 2016;12:CD007026.Google Scholar