Acute ischemic stroke: improving access to intravenous tissue plasminogen activator

ABSTRACT

Introduction

Since approval by the United States Food and Drug Administration in 1996, alteplase utilization rates for acute ischemic stroke have increased. Despite its efficacy for improving stroke outcomes, however, the majority of ischemic stroke patients still do not receive alteplase. To address this issue, different methods for improving access to alteplase have been tested with varying degrees of success.

Areas covered

This article gives an overview of the recent approaches pursued to improve access to alteplase for acute ischemic stroke patients. Utilization of stroke systems of care, quality metrics, and quality-improvement initiatives to improve alteplase treatment rates are discussed. The implementation of Telestroke networks to improve access and timely evaluation by a stroke specialist are also reviewed. Lastly, this review discusses the use of neuroimaging techniques to identify alteplase candidates in stroke of unknown symptom onset or beyond the 4.5-h treatment window.

Expert commentary

Expanding access to alteplase therapy for acute ischemic stroke is a multi-faceted approach. Specific considerations based on region, population, and health-care resources should be considered for each strategy. Neuroimaging approaches to identify alteplase-eligible patients beyond the 4.5-h treatment window are a recent development in acute stroke care that holds promise for increasing alteplase treatment rates.

KEYWORDS:

• Alteplase
• systems of care
• telestroke
• thrombolysis
• ischemic stroke

Article highlights

• Alteplase is proven to be safe and effective for treatment of acute ischemic stroke up to 4.5 h from last known well.

• Utilization rates for alteplase remain low worldwide.

• Stroke systems of care, tracking of quality metrics, and quality-improvement initiatives have improved access to alteplase and resulted in better patient outcomes.

• Telestroke networks have steadily expanded and have resulted in increased alteplase utilization.

• Population education and outreach initiatives can be customized for specific populations and have shown to improve stroke awareness.

• Neuroimaging techniques as a radiographic ‘time-stamp’ of stroke onset or to identify significant ischemic core:penumbral mismatch, are clinically feasible for guiding alteplase treatment in patients with stroke of undetermined onset, beyond the conventional time window of 4.5 h since last known well, and may improve long-term outcomes.

Abbreviations

Tissue plasminogen activator (tPA), acute ischemic stroke (AIS), Last Known Well (LKW), Comprehensive Stroke Centers (CSC), Primary Stroke Center (PSC), Mobile Stroke Units (MSU), computed tomography (CT), magnetic resonance imaging (MRI), fluid-attenuated inversion recovery (FLAIR).

Acknowledgments

The authors thank Ms. Danielle Trota, B.S. and Ms. Joyce McIntyre, M.Ed., M.S.N., R.N. for providing the telestroke and alteplase utilization data from our local databases.

Declaration of interest

LH Schwamm reports the following relationships relevant to research grants or companies that manufacture products for telemedicine, thrombolysis or thrombectomy: scientific consultant regarding trial design and conduct to Genentech (late window thrombolysis); user interface design and usability to LifeImage (and holds <1% stock options in this privately held company); stroke systems of care to the Massachusetts Dept of Public Health; member of a Data Safety Monitoring Board (DSMB) for Penumbra (Separator 3D NCT01584609, last payment 2016; MIND NCT03342664, CURRENT); Diffusion Pharma PHAST-TSC NCT03763929, CURRENT); National PI or member of National Steering Committee for Medtronic (Victory AF NCT01693120, last payment 2015; Stroke AF NCT02700945, CURRENT); PI, late window thrombolysis trial, NINDS (P50NS051343, MR WITNESS NCT01282242; last payment 2017 and alteplase provided free of charge to Massachusetts General Hospital as well as supplemental per-patient payments to participating sites last payment 2017); PI, StrokeNet Network NINDS (New England Regional Coordinating Center U24NS107243, CURENT); Co-I, The Impact of Telestroke on Patterns of Care and Long-Term Outcomes, NINDS (R01NS111952; CURRENT); Co-I, REACH-PC, PCORI (NCT03375489; CURRENT); Member of steering committee, Genentech (TIMELESS NCT03785678, CURRENT). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.