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.

  • There are many things that are a fate worth than death, but most people don’t really care. They won’t take the steps necessary to avoid such a fate.

  • What is the percentage of patients that get the drug that get 100% recovery? Who is working on the drugs that stop excitotoxicity, glutamate poisoning and closed capillaries due to pericytes?

  • Jevria

    TPA benefits 9out of 10 IScheamic strokes o really
    What about the mild stroke patients who would benefit so much
    More without out the drug.Without the very real risk of it
    Causing a major brain bleed.This drug is used for blood clots what about
    Plaque occlusions does it help them or does it do
    More harm than good???What ever happened to the motto
    From doctors Cause no harm!!

  • Jevria

    Mr Simmons I would love a response from you to me.
    All I read from you about TPA is that it is safe.Safe
    How?Have you yourself suffered a stroke and TPA was
    Administered and it worked or have you yourself
    Administered it to a stroke patient and you saw a miraculous
    Recovery.Because truly in my opinion and I’m not even a neurologist.
    I truly don’t believe I need to be to say it is a lethal injection.
    I have seen first hand what this drug does.It destroys the blood
    Brain barrier it causes mild stroke patients to bleed out in there brain.A
    Drug which has supposedly so much promise isn’t
    Suppose to do that.It is’nt suppose to end a young mans
    Life.A father a husband a brother a son.This drug that you swear by
    Doesnt just take lives in my fathers case it caused a heamorrage in my
    Fathers brain stem so the rest of his brain was still functioning.He was locked in for
    My god if there is a hell my father lived it for the last
    Five days of his life.We my mother my brothers and my self
    Had to witness it.Not because it was a major stroke but this
    Drug.To you it means nothing but to us it meant watching
    Our father breath his last breath.Our father our inspiration
    Our drive.A man that worked his whole life to put his children
    Through school.Four months later, today, we lost him and we are
    Broken.In pieces and I guess you are you.

    • John Simmons

      Dear Jevria,

      I’m sorry to hear about your father’s stroke. My sympathy extends to you and your family.

    • Tuan Nguyen

      Samething happen to my brother. He died about four months later after he was injected with TPA.

  • ilia_yasny
  • Tuan Nguyen

    This is the comment from Mike Dudley in another website. His comment talked about what is the outcome of TPA that his 50 years old wife had and the result that affect his family life. I agreed with him 100% because I had seen how my brother family went through for him; but I would said that my brother family was lucky because he passed away four months later. If my brother continues to live for many years, oh my it will make his family bankruptcy for sure and probably ruin his wife or his children life.

    Mike Dudley
    • 4 years ago


    My 50 year old Wife had a stroke while getting ready for work about 18 months ago. I called 911 and she was in the stroke clinic very quickly. Unfortunatly, the Neurologist recommended that they give her tPA to speed her recovery. Both her and I were scared and of course said yes to the treatment. She had improved from an 8 to a 4 and only 1 hour had passed. After they gave her the tPA, they sent her to critical care for obsevation. It’s a long story, but briefly, she was moving both arms and legs when she got the tPA and as the day progressed, I noticed she was getting worse. I kept telling the nurses she was getting worse. They said it was just the resut of her getting tired. Late that night I went home for a little sleep. Soon after I fell asleep, I was woke up by the police telling me that I need to get to the hospital, they need my consent to do emergency brain surgery on my wife. The tPA had cused her to bleed in her brain and the pressure was killing her. I made it there and the surgery to stop the bleeding was succesful. Now, after 18 long months of therapy, 500,000.00 dollars worth of medical bills and constant depression, crying, and the realization that our lives are over, my Wife is parilyzed on her left side, she has left side neglect, left side vision split, and short term memory problems. Because she got tPA, our lives have been ruined forever! I am sick of reading about how great tPA is! Check the facts. Many of the people that get tPA for stroke, recover no better than they would have without it, and it causes about 6 percent to bleed like my wife. Roughly half of the people that bleed die. My wife often says she wishes it would have killed her instead of having to live like this. It makes no sence for the doctor to ask for your consent to give tPA, you are most likely not even close to being qualified to make that decision, especially in the crtical and emotional situation you are in. It is absolutly agonizing for me to see my wife suffering like this. Except to help my wife dress, bath, eat, go to the bathroom, etc, I really feel like I have nothing to live for anymore. My grandchildren? Not really, the kids, like everyone else, avoid us whenever possible. I love my wife so much and, in my opinion, we had a perfect marrage. Now, not only have my wife and I lost everything that we had together in terms of our marrage. I lost my job. I worked for a small company that has a self insured health care benifit. Yes, the economy slowed down, but during the slow down, they implemented rotating layoffs. I was not part of that. My position was eliminated. In the last benefit meeting I attended, they showed the medical claims paid out for last year. Our claims were huge in comparison. I can’t prove anything, but I worked there for over 30 years and I know how things work around there. Recent new management has a very comprehensive profit plan and the CEO is always talking about health insurance. The slow down made it easier for them. The list of problems that tPA has caused goes on and on. Many in the health care system are quick to endorse this very expensive and highly controversial drug. However, when they destroy an entire family with a single dose, they are quick to turn their back on them while they reap the huge additional profits the resulting carnage has generated. They seem to be saying that because tPA has helped a few people, the total devistation that we have suffered is justified. If this had happened to their wife and their family, I believe they would have a much differnt opinion. I would never allow anyone I love to recieve tPA again, NEVER!

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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