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Review
. 2015 Jul;5(3):101-9.
doi: 10.1177/1941874415583116.

Intravenous Thrombolysis for Acute Ischemic Stroke Within 3 Hours Versus Between 3 and 4.5 Hours of Symptom Onset

Natalie T Cheng  1 , Anthony S Kim  1
Affiliations
Review

Intravenous Thrombolysis for Acute Ischemic Stroke Within 3 Hours Versus Between 3 and 4.5 Hours of Symptom Onset

Natalie T Cheng et al. Neurohospitalist. 2015 Jul.

Abstract

Data from randomized clinical trials have supported the safety and efficacy of intravenous tissue-type plasminogen activator (IV tPA) for acute ischemic stroke when administered within 3 hours of symptom onset, and regulatory approvals for this indication have been in place for almost 20 years. However, recent clinical trials have provided evidence that IV tPA may be safe and effective in selected patients up to 4.5 hours after symptom onset, thereby increasing the proportion of patients that may be eligible for treatment. Although professional organizations in the United States and many regulatory agencies internationally have supported this expanded time window for IV tPA, the US Food and Drug Administration has declined to approve this expanded indication and so this use of IV tPA has remained off-label in the United States. Here we review the current evidence for IV tPA in the standard and the expanded time windows and the data on current clinical practice in the United States as it relates to IV tPA treatment for acute stroke within 3 to 4.5 hours of symptom onset.

Keywords: cerebrovascular disorders; clinical specialty; clinical trials; stroke; stroke and cerebrovascular disease; techniques.

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Conflict of interest statement

Declaration of Conflicting Interests: ASK receives research grant support from NIH/NCATS for unrelated work, NIH/NINDS for stroke research and from SanBio Inc. for stroke research unrelated to this article.

Figures

Figure 1.
Figure 1.
World map of countries with IV tPA approval in the 3- to 4.5-hour window as of January 20, 2014 (courtesy of Peter Schillinger and Boeringer-Ingelheim).
Figure 2.
Figure 2.
Time line of major IV tPA trials and regulatory approvals. ECASS indicates European Cooperative Acute Stroke Study; NINDS, National Institute of Neurological Disorders and Stroke tPA Trial; ATLANTIS, Alteplase ThromboLysis for Acute Noninterventional Therapy in Ischemic Stroke; EPITHET, Echoplanar Imaging Thrombolytic Evaluation Trial; SITS-ISTR, Safe Implementation of Thrombolysis in Stroke—International Stroke Treatment Registry; FDA, Food and Drug Administration; AHA/ASA, American Heart Association/American Stroke Association.
Figure 3.
Figure 3.
Number needed to treat to benefit and harm per 100 patients treated with intravenous recombinant tissue-type plasminogen activator (IV tPA) for acute ischemic stroke in the <3-hour versus 3- to 4.5-hour time windows. mRS indicates modified Rankin scale; NINDS, National Institute of Neurologic Disorders and Stroke; ECASS-III, European Cooperative Acute Stroke Study-III.
See this image and copyright information in PMC

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