Intravenous alteplase for acute ischemic stroke: when and when not to use

By Will Boggs MD

NEW YORK (Reuters Health) - Extensive recommendations in a new scientific statement from the American Heart Association/American Stroke Association (AHA/ASA) detail when it is appropriate and not appropriate to administer intravenous alteplase for acute ischemic stroke.

Although approved 20 years ago and well established as a treatment for acute ischemic stroke, the recombinant tissue-type plasminogen activator (tPA) has been used for only 3% to 5% of patients with acute ischemic stroke.

Dr. Bart M. Demaerschalk (chair), Dr. Dawn O. Kleindorfer (vice chair), and colleagues on the AHA Stroke Council and Council on Epidemiology and Prevention reviewed the guidelines and exclusions, warnings, risks, and contraindications for alteplase, the only tPA licensed for use in acute ischemic stroke, and settled on more than 90 recommendations for its use in a variety of settings.

Many of the recommendations reassert the label indication for alteplase: intravenous thrombolysis with alteplase is indicated within three hours after the onset of stroke symptoms for the management of acute ischemic stroke in adults for improving neurological recovery and reducing the incidence of disability after exclusion of intracranial hemorrhage.

The label advises caution for patients >75 years of age and notes that the safety and effectiveness of alteplase have not been established for pediatric patients.

Based on available information, the new recommendations support its use in patients <80 and >80 years of age, because alteplase provides a better chance of being independent across all age groups. They retain the caution that its use in pediatric populations is not well established.

The previous Food and Drug Administration label did not recommend alteplase treatment for patients with minor or improving deficits or for patients who present later than three hours after symptom onset.

These recommendations support the use of alteplase regardless of symptom severity and even for patients with early improvement (while emphasizing the need to balance risks against possible benefits). The guideline also recommends treatment for eligible patients who can be treated within three to 4.5 hours after stroke onset.

Intravenous alteplase should not be given to patients with acute intracranial hemorrhage and probably should be withheld from patients with coagulopathies or thrombocytopenia.

However, alteplase should be considered for otherwise eligible patients who are pregnant or who have undergone major surgery or had major trauma in the preceding 14 days, but severe head trauma within three months is a contraindication.

Other recommendations address the appropriateness of administering alteplase in the setting of acute or recent myocardial infarction, pericarditis, left-sided heart thrombus, infective endocarditis, recent history of intracranial/spinal surgery, recent ischemic stroke, recent gastrointestinal bleeding, history of intracranial hemorrhage, and numerous others.

Alteplase is not recommend for patients who awake with a stroke or have an unwitnessed stroke beyond three to 4.5 hours after a normal baseline state, and imaging criteria should not be used to make a treatment decision in these patients (outside a clinical trial).

Dr. Kevin N. Sheth, from Yale School of Medicine's Division of Neurocritical Care and Emergency Neurology, New Haven, Connecticut, told Reuters Health by email, "The main things that are new are significantly increased clarity on a wide range of considerations that emergency and acute stroke physicians face, as well as the data to support those decisions. In my opinion, there is little that is controversial but much that is clarifying."

"Practitioners should really pause before they withhold tPA for what may have been previously considered a 'relative contraindication,'" Dr. Sheth concluded. "We need more research to identify who is at high risk of hemorrhagic transformation and to support therapies designed to protect against it."

The full Scientific Statement, published online December 23 in Stroke, also includes a comparison of AHA/ASA acute stroke management guidelines with previous and new FDA prescribing information for alteplase treatment in acute ischemic stroke.

Dr. Demaerschalk and Dr. Kleindorfer did not respond to requests for comments.

Four coauthors reported disclosures.


Stroke 2015.

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