Into the Looking Glass – Stroke, tPA, and Avoiding a Fate Worse Than Death

Stroke, a major cause of death and the leading cause of adult disability, can leave victims unable to walk, talk, eat or take care of themselves. To treat stroke while it’s happening, the “clot-busting” drug tPA (tissue plasminogen activator) has been proven to save brains from damage and reduce or even completely avoid disability. Patients require a CAT-scan to assure diagnosis and the drug must be administered within 4.5 hours after onset of symptoms. In today’s medical environment, that shouldn’t be an overwhelming obstacle.

Although appropriate for almost 9 in 10 strokes — those that are ischemic, or due to blood clots — only a small fraction of potentially eligible patients, not more than about 4-8%, receive tPA.  Consider this:

It’s safe and effective…so few patients get it. As a drug for a major and life-threatening disorder, tPA was shown to be effective with a 11-13% absolute benefit (cancer drugs that provide a 2% absolute benefit are routinely approved).

It’s a one-time drug…yet so became the target of a muckraking campaign. Unlike drugs such as Vioxx, which were prescribed for daily use to masses of patients only to show unanticipated adverse effects, tPA for stroke is usually given once, intravenously. But its approval nevertheless incited journalists to campaign against it as dangerous and ineffective. Such charges lingered for years after post-approval studies confirmed the original results of randomized trials, which were supported not by the drug industry but by a branch of the National Institutes of Health.

Neurologists never had a drug to treat stroke before…so they were reluctant to use this one. Many neurologists might have been expected to be early adopters but initially only a few were enthusiastic. Neurologists were not accustomed to treating strokes as the emergencies they demonstrably are, and  many remained skeptical for years. Most have been by now been convinced, but tPA has been the most controversial drug ever used in neurology.

Emergency physicians were accustomed to using tPA… yet with stroke they didn’t want to. When the drug was first FDA-approved, ER doctors often used it for heart attack (most commonly due to clots, like stroke). But when it came to a brain disease, many (despite their reputation as cowboys in the ER) were fearful and concerned about their diagnostic acumen. A few created and many bought into the efforts to impugn tPA as overhyped by its manufacturer, Genentech, presumably in cahoots with the American Heart Association.

Stroke victims don’t know about tPA. Although controversies over the drug are now largely past, their legacy has been persistent lack of stroke awareness among the general public, with only a small minority of potential patients and their families or colleagues knowing the symptoms of stroke,  the importance of time-to-treatment, or the simple instruction (Call 911). So it is that, although FDA-approved for stroke since 1996, tPA today reaches only a fraction of nearly 800,000 new stroke victims annually in the United States. About 50% are potentially eligible.


Adeoye O, Hornung R, Khatri P, & Kleindorfer D (2011). Recombinant tissue-type plasminogen activator use for ischemic stroke in the United States: a doubling of treatment rates over the course of 5 years. Stroke; a journal of cerebral circulation, 42 (7), 1952-5 PMID: 21636813

Zivin JA, Simmons J. tPA for stroke: the story of a controversial drug. New York: Oxford University Press; 2011.

Image via andkuch / Shutterstock.

John Galbraith Simmons

John Galbraith Simmons writes about science and medicine for both general and professional audiences and is the author, most recently, of "tPA for Stroke: The Story of a Controversial Drug" (Oxford Univ Press), written in collaboration with Justin A. Zivin MD, PhD.
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