Optimizing the management of acute ischaemic stroke: a review of the utilization of intravenous recombinant tissue plasminogen activator (tPA)

Abstract

What is known and objective: Thrombolysis using intravenous tissue plasminogen activator (tPA) is the only available evidence-based treatment for acute ischaemic stroke; however, its current utilization is very low. Therefore, the aim of this article is to review the literature regarding the use of intravenous tPA for the treatment of acute ischaemic stroke. The review will also compare utilization rates of thrombolysis in different centres across the world and identify key reasons for the underutilization of thrombolysis in stroke.

Methods: MEDLINE, EMBASE, International Pharmaceutical Abstracts (IPA) and Google Scholar were searched for relevant original articles, review papers and other publications over the publication period 1995-2012.

Results and discussion: The National Institute of Neurological Disorders and Stroke (NINDS) (1995, N = 624 patients) and ECASS III (2008, N = 821 patients) are two pivotal randomized controlled trials providing evidence for the use of intravenous tPA within 3 h or 3-4.5 h from stroke onset, respectively. Both trials have shown that tPA administration decreases disability at 90 days from stroke. Furthermore, a recent pooled analysis of randomized controlled trials (2010, N = 3670 patients) supports these results, highlighting that early stroke treatment is associated with better outcomes, especially when treatment is started within 90 min of stroke onset (but suggesting that the benefit could be afforded within a 4.5-h time window). Three major observational trials, STARS (2000, N = 389 patients), CASES (2005, N = 1135 patients) and SITS-MOST (2007, N = 6483 patients), have reported acceptable safety and efficacy in clinical practice. However, only a small proportion of acute ischaemic stroke patients receive tPA in clinical practice, because of the limited availability of tPA-utilizing sites and suboptimal use of tPA in sites where it is available.

What is new and conclusion: tPA reduces disability in stroke patients. Moreover, acceptable safety has been demonstrated in routine clinical practice. However, tPA is significantly underutilized, and specific efforts are needed to encourage appropriate implementation of the stroke treatment guidelines to optimize the use of this important therapy.