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The jury is still out among EPs as to whether tPA helps more than it hurts, yet ACEP has forged ahead with clinical guidelines which seem to ignore controversial findings.     

The British Medical Journal recently published a piece by the medical investigative reporter, Jeanne Lenser,  in which she recalled the political pressure that was brought to bear on emergency physicians to administer high dose steroids in spinal cord trauma, despite serious misgivings among neurosurgeons concerning its efficacy and safety.  Now it seems, in her mind, that history is repeating itself with the use of tPA in stroke. “Earlier this year,” Lenser writes, “the American College of Emergency Physicians with the American Academy of Neurology (jointly) and the American Heart Association, separately, issued grade A level of evidence guidelines for alteplase in acute stroke. The simultaneous recommendation by three respected professional societies would seem to indicate overwhelming support for the treatment and consistent evidence.” Lenser counters this statement with the results of an online poll of 548 emergency physicians in which only 16% support the new guidelines.

In order to test these numbers further, Emergency Physicians Monthly conducted its own informal online poll. Out of about 16,000 emergency physicians polled we received more than 1,300 responses. We found that while 67% of EPs would want to be given tPA if they or a loved one had stroke symptoms, less than half that number, 32% of the total polled, “believe the research shows a small but significant possibility of improved outcome.” The other half of those who would give the drug would rather “die with a hemorrhage than run the risk of not improving,” a rationale that is heavily influenced by moral choice over medical reasoning.

With such tepid support for tPA in stroke among EPs, how did the College decide to bind its membership to this guideline? Lenser claims that the committee that approved the policy was stacked with physicians who had direct or indirect financial ties to the drug industry. Readers should examine her claims for themselves. But the larger question is why are so many EPs willing to go along with this decision?

When EPM polled EPs as to why they give tPA to their patients with stroke symptoms, the majority, 61%, did so not because they thought it would work, but because they were “afraid of getting sued if I don’t” (12%), deferred to the presumed judgement of the neurologists at their hospital (33%), gave it despite believing it could harm the patient (8%), or just didn’t know why they used the drug (8%).

In other words, while many emergency physicians familiar with the tPA research feel that the evidence in support of use of the drug is inconclusive and may even suggest potential for harm that outweighs the benefits (see last months article by David Newman), there are multiple factors encouraging the use of the drug. On one hand, there is compulsion. EPs now find themselves compelled by ACEP’s published guidelines, hospital administrators, and others within the stroke power structure to use the drug. Even more influential, EPs have found themselves being sued for deciding not to administer the drug. On the other hand, doctors come under the subjective moral pressure of choosing the lesser of two unknown evils. We see this in EPs who are willing to use a drug on themselves and others that they think could as likely kill them as help them.

Why do we do this? Because we want it to work. In 1982, I was personally involved in the research of high dose steroids in spinal trauma. All of us involved in the research wanted a cure for this devastating condition so bad that we could see its cure around the corner. In fact, a research paper that I presented as a senior EM resident made the unfounded leap to propose the high dose steroid protocol that was eventually introduced as the “Jefferson Protocol” ten years later. Early results of some studies suggested such benefits that the protocol gained early wide acceptance and was even mandated in some circumstances. But later studies questioned the earlier results, particularly with respect to the risks of death from the side effects of the drug itself.

Similarly, tPA holds out the possibility for a ‘cure’ of a devastating disease. And that’s why we all went into this field – to fix things.  As emergency physicians, we want it to work. If you have ever given tPA in an ischemic stroke and have seen the patients symptoms resolve before your very eyes, you will be a ‘believer’ and want to give that benefit to future patients. And if trusted researchers tell you the drug is safe and effective, that’s all most of us need.

Unfortunately, our overly optimistic desire for a cure isn’t our only obstacle to overcome with tPA. As Lenser points out in the BMJ, we have to question the very experts who provide us with the data. We know that many research analysts and learned scholars disagree on whether the evidence for efficacy of tPA in stroke overcomes its potential for devastating side effects, particularly intracranial hemorrhage. But who do you believe when researchers who support a therapy have financial gain from doing so? That is not to say that anyone was untruthful or misleading in creating these guidelines. But it raises questions about objectivity that must be weighed as we consider whether use of the drug is, or should be, the standard of care.

I’m not calling anyone out, but I know the benefits that accrue for those who are on the leading edge of a cure for such a devastating condition. Anonymous researchers suddenly emerge from the bowels of the lab to the sunlight of accolades, honor, celebrity, and money. Kevin Klauer wrote last month about going beyond admitting bias in physician promotion of certain treatments to outright banning involvement of any physician who profits from his clinical position. While it is altogether appropriate, it might be a bit difficult in practice. Researchers are proud of the work they do. They believe in it. They feel that the aberrations in the data are completely explainable. They want to talk about it. And if that helps a drug company, the drug company is more than happy to pay them and cover their expenses for doing so. Does it suggest bias in their discussions? Absolutely. Does it invalidate their research? No, but it must be taken into account when weighing the validity of their claims. Might it take years to get the same information out by other less biased methods? Probably so.

So what is a drug company to do when clinicians are on the fence about using a new ‘breakthrough’ drug that has the potential for significant side effects? This is where it gets really sticky. No one can question the brilliance of the “Time is Brain” marketing concept. Who can resist that? Madison Avenue doesn’t make the products, it just sells them. But when the guidelines are based on controversial medical evidence, maybe we should be in that driver’s seat.

With regards to tPA, the ground swell of desire – both pure and profiting – to cure this disease birthed the concept of ‘stroke centers’. Shouldn’t every stroke patient get the benefit of the best care? Stroke Centers make nerdy neurologists into life savers. Stroke Centers give the public the impression that this devastating disease can be reversed (read cured) just like we seem to have ‘cured’ heart attacks with cath labs. It even makes some intuitive sense. There is good evidence that hospitals which do a lot of stroke care usually do it better. From immediate management of stroke symptoms to long term stroke care and rehabilitation, those with the most experience usually get better results. Stroke centers make politicians and hospital administrators happy. They make money, particularly in an age of graying populations. But does that mean that patients treated at stroke centers must be given tPA? Unfortunately, the controversy over the scientific evidence tends to get lost; indeed, one of the requirements of being a designated stroke center is that they must be trained to administer tPA. And training goes along with the implication that use of the drug is the standard of care. But is it? Well, that depends on whether the standard of care is what the average physician actually does or what he/she should do in the eyes of a committee of experts. What would you do?

“I’m a 43 year old with a concerning family history,” says Dr. David Newman. “If I have a stroke – and I may – I don’t want anyone slipping a wire into my brain, or infusing me with a powerful drug, unless or until the science shows convincingly that I am substantially more likely to recover because of it.” Newman, a physician and author based in New York, explains his rationale by saying, “My human body has a million years of evolution supporting it, and I will most likely recover without a drug in the acute phase. I do want rehab, and team stroke care, and lots of support, but I do not want anyone mucking around with my finely tuned (if I do say so myself) machine until there’s proof that it works. Indeed that is the standard that I believe patients presume and expect, and it’s the same standard that I want applied to me when I need help.”

“My point of view is rather pragmatic,” says Dr. Rick Bukata, founder of Emergency Medical Abstracts. “I may, depending on the level of my compromise, decide to take a chance and be willing to suffer the consequences if I were substantially compromised. I know the worse the stroke, the worse that people do with tPA. So I may want the option to roll the dice. I certainly don’t want this option taken from me by tPA being given without any consideration for my opinion.”

Dr. Jerry Hoffman, a nationally-respected educator who has been a key voice in this debate since the beginning, takes a much more definitive stance when asked if he would want tPA after experiencing a stroke.

“Nope – not I. I used to say I don’t know if it’s a good idea; so, I’d want to be in a trial, and get randomized. After all this time, though, and all the evidence that we do have (inconclusive though it is), I’ve switched to ‘clearly no’ – I wouldn’t want it. I do acknowledge that the evidence is not definitive, but it’s good enough to say that it’s extremely unlikely that tPA is useful in any important way. I’d also say that it’s probably worse than neutral.  Similarly, I admit that there may be some small subgroup who could benefit, but even that’s unlikely, I think. And furthermore, we certainly don’t know who that group might be (even if it exists). I’d be happy to change my mind, if new studies said the opposite. By now, though, the likelihood that that would ever happen (if they did the appropriate studies, which would be a shocker in itself) has become vanishingly small.”

When you ask how EPs would treat themselves or someone near and dear to them, if they had a stroke, you get both rational and emotional decisions. In some, the fear of living with hemiplegia is strong enough to push us to use a therapy that could kill us. To borrow Dr. Bukata’s language, it seems to really come down to a roll of the dice. Would you or your patient rather take a chance on dying from a intracranial hemorrhage in the hopes that you might be one of the small group that might benefit from the drug. Or would you rather play it ‘safe’ and hope that stroke rehab is good where you are.  It seems rather clear that this is a decision only a patient can decide for himself. And this decision needs to be one based on personal goals and values.

So is this a simple academic discussion or does it call for action? I, for one, think the latter.

First, there needs to be an open discussion of the research concerning tPA in stroke, involving emergency physicians and neurologists, one that reveals all the financial ties of anyone involved, and includes the dissenting voices. Since ACEP has promoted the guidelines they have the responsibility for conducting such discussions.  Whether the College does this or not, look for EPM to have such roundtable discussions in the coming months, in print and on-line.

Second, if, as I suspect, the conclusions will remain controversial, this should be clearly communicated to every patient and their family who is faced with the decision whether to use tPA. And they should be the only one to make an informed risk/benefit assessment for themselves and their loved ones.

Third, ACEP should make it absolutely clear that use of tPA in stroke is NOT the standard of care and experts who testify otherwise in court should be exposed as testifying falsely.

And last, stroke center designation should be completely and clearly severed from any real or perceived requirement or expectation to administer the drug to their patients.

This month EPM asked 17,003 emergency physicians how they felt about tPA and stroke.
1,333 physicians (7.8%) responded.
>>Here’s what you told us>>

Dr. Plaster is the founder and Executive Editor of Emergency Physicians Monthly



 

Comments   

# Brian Dillon 2013-08-15 10:28
Congratulations to Mark on excellent essay. Also to Jenny who's reports are always Insightful.
I think the TPA Issue is a huge problem In emergency medicine. Thank about it ,rarely are we asked or forced to do something that we know will probably cause harm to the patient not benefit them. That is with the literature shows. It is clear. Yet we get sued frequently if we do not. However if you give it and have a bad outcome you also get sued. The underlying problem is manufacturer funded studies. Why is Heart Association in charge of strokes anyway. Was it because Genentech paid For their new building?
Maybe we need government or University funded trials only in the future.
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