Knock ‘em alive: tPA is a drug that can eliminate the adverse effects of the stroke; An interview with Justin Zivin, M.D., Ph.D.

Justin Zivin, M.D., Ph.D., co-discovered tissue plasminogen activator, or tPA, an enzyme that the human body could use to combat the effects of stroke.  Statistics say that a person will be100% ‘back to normal’ when you leave the hospitals. It is, to this day, the only FDA-approved remedy there is for an acute ischemic stroke.  Dr. Zivin is the co-author of tPA for Stroke: The Story of a Controversial Drug, along with John Galbraith Simmons.  They review the financial, medical, political contentions with tPA, and offer a chance through the eyes of public education to demystify the inaccuracies.

“Doctors must be led by the people.” – Justin Zivin, M.D., Ph.D.

Knock ‘em alive: tPA is a drug that can eliminate the adverse effects of the stroke

By Marcy Shugert
October 11, 2011

Justin Zivin, M.D., Ph.D., a professor of neurosciences at University of California, San Diego, sat in front of me at his desk at the Veterans Association Hospital (where he is also a physician), surrounded by journals, medical newsletters, Food and Drug Administration (FDA) correspondence, files, etc. Dr. Zivin is a well-authored individual, having written many journal articles from when he first started studying the brain in the early 70′s. He is a well-known doctor for stroke, and co-discovered tissue plasminogen activator, or tPA, to be an enzyme that the human body could use to combat the effects of stroke. It is, to this day, the only FDA-approved remedy there is for an acute ischemic stroke.

We have met before this, me as his patient almost two years ago, and at that time, he told me about tPA, and how it isn’t well-marketed throughout the hospitals, and overall, to the general public. He is the co-author of tPA for Stroke: The Story of a Controversial Drug, along with John Galbraith Simmons.

After researching tPA, I realize how important it is to get this information out to the general public. When I mention tPA to friends and family, I’m disappointed that they have not heard of the drug, despite the fact that tPA can alleviate stroke effects, including:

  • hemiparesis [weakness on one side of the body]
  • hemiplegia [total paralysis of one side of the body]
  • short-term or long-term memory loss
  • aphasia [having difficulty remembering words to being completely unable to speak, read, or write]
  • apraxia [loss of the ability to execute or carry out learned purposeful movements, despite having the desire and the physical ability to perform the movements]
  • cognitive difficulties

tPA is a protein that is released naturally by the body that breaks down blood clots. Commercially, it is called Activase® (Alteplase) made by pharmaceutical company Genetech, approved by the FDA in 1996.

It is not without drawbacks. Studies have shown that tPA use can result in:

  • hyperfibrinolysis, a markedly enhanced blood flow, resulting in increased or catastrophic bleeding
  • symptomatic intracranial hemorrhage (ICH), or more commonly called a brain bleed.

As a result of these side effects, the FDA put restrictions on it, saying that it could not be administered after 3 hours of the onset of stroke symptoms in the U.S. (it is approved by the European and Canadian markets by European Cooperative Acute Stroke Study [ECASS] III) for up to 4.5 hours from the stroke symptoms occur).

In tPA for Stroke: The Story of a Controversial Drug, Dr. Zivin and Mr. Galbraith outline the trouble that tPA has come across over the years: Financial, Medical, Political and Public Education. I have gone over them briefly here (they go in a lot more detail in the book).


For one injection – and that is all you need – it costs about $2,000. Medicare will pay back most of that, though not all of it. Right now, it is more beneficial from a cost standpoint to get a hospital to administer tPA; “they get in effect $11-$12K when someone gets tPA,” says Dr. Zivinn, and “private insurance takes their cues from Medicare.”

On the flip side, the American Heart Association and American Stroke Association estimates that stroke will cost the country about $68.9 billion in 2009.[1]  This total includes health care services, medications, and lost productivity due to illness or death. It would be more cost-beneficial to administer tPA to eligible patients.

Dr. Zivin comments, “we only have so many dollars where we can make decisions on medical care. In other countries, they base it on medical need, but in this country, they base it on cost.”


In the 1970′s, Elliott Grossbard, M.D., a Cardiologist, told Dr. Zivin that there was no cure for the stroke. But Dr. Zivin didn’t believe him; he replied that Dr. Grossbard “was telling me dogma and I have always been an iconoclast”.

Dr. Zivin said that he had the advantage over many doctors in that he had graduate school training, so he learned how to independently evaluate the material he was reading. “It caused me some problems when I was a resident”, he comments. “My chairman said to me, for instance, ‘Don’t you read the literature?’ And I said, ‘Yes, I read, and told him the journals that I read.’ And he said, ‘Why don’t you quote it?’ And I said, ‘Because I think it is lousy.’ And he said, ‘But it’s all we have got.’ And I said, ‘But it is not good enough.’”

So that lead to searching tPA for stopping ischemic strokes in the late 70′s, with Désiré Collen, M.D., a biochemist and physician, running a laboratory in Europe.

Fast forward to 1996, it was presented by Genentech, and accepted by FDA. When it was introduced to hospitals, neurologists were not accustomed to dealing with neurological emergencies because it was thought that, akin to Dr. Grossbard, strokes could not be cured. And it was going to require the neurologists to change their style of practice in order to take care of those patients that needed care 24 hours a day.

The results of the trial were published slowly (3 or 4 years later), and the naysayers jumped at the chance to criticize the overall method of Genentech’s trials.

Meanwhile, the Emergency Room physicians were looking for Neurologists to take over when the stroke patients came in, and a lot of places just weren’t ready to do that. Actually, it was somewhat of a “revolution” to have a Neurologist to be available outside of office hours. To do that, an Emergency Room doctor, Neurologist, Radiologist (to do a CT scan/echocardiogram/MRI), and Nurses all have to be on staff. “Eventually it became clear that,” Dr. Zivin commented, “ten years down the line [in 2006], that my view was the ER doctors should know how to deal with this stuff on their own. And it was at that time I wrote the book tPA for Stroke: The Story of a Controversial Drug to encourage them to do the right thing.”


So now that various medical staff members are aware of it, there is still some circumspect about using tPA. The senior Neurologists don’t think it works because of the complications. On the other hand, the younger Neurologists are starting to understand that with proper explanation to the patient, they can administer it when they have got the evidence from the radiologist and the patient they need.

However, Dr. Zivin commented, “the National Institute of Health (NIH) does not have any obligation to do anything about [the marketing of tPA], though sponsored the trial and they helped to write the guidelines to how it should be used.”

So Dr. Zivin went to the AHA/ASA, a major proponent of tPA, about five years ago and he said he has a Public Service Announcement (PSA) that tells people about strokes, having Sharon Stone speak, along with others that have had a stroke. Dr. Zivin proposed that the AHA/ASA put them on during the Super Bowl. They had about $36 million in advertising dollars, and it would be $6 million for one of his ads to play, which he did not have. The PSAs were ultimately donated to AHA/ASA, but nothing yet has materialized.

Then the lawsuits started between the patients and the ER physicians/Neurologists. “It wasn’t anything I enjoyed doing,” says Dr. Zivin, “but I thought it was necessary in order to frighten the ER docs into giving the drug properly.”

Public Education

Stroke is a disease that is the number two killer in the world[2] and will affect ~800,000 per year, and kills nearly 140,000 per year. Twenty-eight percent are people under the age of 65 in the United States. Every three minutes, someone dies of a stroke in the U.S.[3]There are two general types of stroke, ischemic (blood-clot) which accounts for approximately 80% of strokes and hemorrhagic (blood burst), which is approximately 20%. Ralph Macco, M.D. says that he numbers are maybe 3% to 5% ischemic strokes per year actually get tPA.[4] And Dr. Zivin “estimates that more than 200,000 stroke victims each year in the U.S. alone could improve or recover completely if treated with tPA.”[5] Almost any hospital can administer tPA, but the hospitals that can administer it best are Stroke Centers, and only about 10% in the U.S. are primary Stroke Centers.

What to do next…

Inform the general public by putting up on Facebook, Google+, Twitter, etc. the causes of the stroke, and that tPA is a drug that can be used for ischemic strokes. A four-year study of 790 participating hospitals showed a 29-percent increase in the percentage of eligible patients who received clot-dissolving drugs [tPA] within two hours of hospital arrival, a measure that can minimize the extent of damage to the brain and prevent permanent disability.[6]

Contact Congress about Get With The Guidelines® (to help hospitals improve outcomes in stroke patients) should be at more hospitals, as stated by the AHA/ASA. Some include, as outlined in Cardiovascular Business this past February:[7]

  • Pre-arrival notification by EMS providers;
  • Written protocols for acute triage and patient flow;
  • Single call systems to activate all stroke team members;
  • CT or MRI scanner clearance as soon as the center is made aware of an incoming patient;
  • Locating the CT scanner in the emergency department (ED);
  • Storage and rapid access to thrombolytic drug in the ED;
  • Collaboration in developing treatment pathways among physicians, nurses, pharmacists and technologists from emergency medicine, neurology and radiology; and
  • Continuous data collection to drive iterative system improvement.

On the good side of things, the hospitals are improving their standards. Gregg C. Fonarow, MD, a professor of cardiovascular medicine at the University of California, Los Angeles, stated, “Nearly 1,000 hospitals across the country are now registered to use Target: Stroke information and tools to improve their door-to-needle time for administering tPA to appropriate stroke patients.”[8]

And influence your local television stations to get the stroke PSAs on air so that they are viewed during prime time hours.

And finally, just read and share the facts with anyone and everyone you know. As Dr. Zivin stated in the beginning of this article, to lead the doctors you have to lead the people. You could save a life.

You can get tPA for Stroke: The Story of a Controversial Drug by Justin Zivin, M.D., Ph.D. and John Galbraith Simmons at Amazon (, or your local bookstore.

  1. [1]   Centers for Disease Control and Prevention, “Stroke Facts,”, last reviewed January 28, 2010
  2. [2] World Health Organization, “The Top Ten Causes of Death,”, February 2007.
  3. [3] Centers for Disease Control and Prevention, “Stroke Facts,”, last reviewed January 28, 2010
  4. [4] Interview with Ralph Sacoo, M.D. from Medscape Medical News , “tPA for Stroke Moving Out to 4.5 Hours,”, last reviewed by September, 07, 2009
  5. [5] Arthur Lightbourn, “Pioneer stroke researcher urges community to advocate for stroke victims nationwide,”, posted January 7, 2011.
  6. [6]  American Heart Association, “Get With Guidelines-Stroke Overview,”, October 7, 2011
  7. [7] Chris Kaiser, “ISC: Less than one-third of stroke patients receive timely thrombolysis,”, updated February 15, 2011
  8. [8] iBid
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