A few months ago, possibly while you weren’t looking, the debate regarding the utility of tissue plasminogen activator (tPA) in acute ischemic stroke was finally settled. Even if Genentech and the American Stroke Association haven’t won over many hearts and minds in the emergency medicine community, the war is effectively over. The forces aligned in favor of tPA fought the battles that mattered by funding the people authoring the guidelines and hospital quality measures, not via sniping in the academic literature. Given the prevailing medicolegal climate in many states, coupled with the institutional interest in stroke center certification and the growing reach of telestroke services, holding out as a conscientious objector to the use of tPA grows ever more perilous.

However, all these factors pale in the context of the public-shaming hit job from The New York Times titled, “For Many Strokes, There’s an Effective Treatment. Why Aren’t Some Doctors Offering It?”¹ If you didn’t read the article, its general tone should be apparent from the title. The author wades into the debate over tPA by pitting the two sides against each other with a biased portrayal of their positions: the neurologists, beleaguered and confused by the opposition to their sterling evidence, and the emergency physicians, which the author described as being led by shyster figurehead Jerome Hoffman, MD, professor of emergency medicine at the University of California, Los Angeles, and his cadre of disinformation trolls on social media. The author effectively implies only the lunatic fringe would contest the efficacy of tPA, and even the lead subject of the article, Christopher Lewandowski, MD, an emergency physician at Henry Ford Hospital in Detroit, is considered a victim. The pervasive reach of anti-tPA dissent, according to this reporting, prevented his father from receiving the blessed miracle of “clot-busting” therapy.

Hyperbole and exaggeration aside, this obviously is not an appropriate characterization of our specialty nor of some of our most respected leaders in the critical appraisal of medical evidence. Also, it isn’t productive to refresh, ad nauseum, the back-and-forth regarding the efficacy of tPA, tweeting out the enrollment imbalances, the effect sizes, or the relative relevance of the trials that did not result in statistically significant positive findings. The most important lessons from this odd article in the Times relate to why, 23 years after the National Institute of Neurological Disorders and Stroke tPA clinical trial was published, such uncertainty persists regarding the appropriate treatment of patients suffering acute ischemic stroke and why it remains such a fiery topic.²

Persistent Uncertainty

First, the practice of the emergency physician has been dictated by outside specialty societies without proper collaboration and appropriate understanding of our specialty. The management controversy associated with acute ischemic stroke is hardly an outlier in emergency medicine. Over the past decades, we have been subject to implementation mandates for early goal-directed therapy (EGDT) for sepsis, recommendations for early provocative testing for patients with chest pain, and high-dose steroids in spinal cord trauma, among countless others. Many of these treatment pathways and recommendations demand profound reorganization of systems of care in the emergency department.

Second, many of these same external edicts ultimately fell victim to medical reversal. The original EGDT protocol has evolved into an entirely different sepsis hydra. The pendulum is swinging back toward a conservative approach to patients with chest pain. The initial enthusiasm for high-dose steroids in spinal cord trauma has given way to concerns over harm and critically flawed methodology.

The same pervasive syndrome of medical reversal affects ED care, even when looking solely at trials published in such journals as The New England Journal of Medicine, Lancet, and JAMA.³ It should be clear by now there is great prudence in allowing additional evidence and evaluation to percolate through academic circles prior to adoption. The longer evidence is allowed to accumulate, the better understanding of patient-level factors influencing individual treatment response can be appreciated.

It’s Not a Slam Dunk

This circles back to tPA. We know tPA administration does not help every patient who receives it. A variety of factors influence whether the clot buster even lyses the clot. A variety of factors influence whether there is actually any surviving tissue behind the clot. Even proponents of tPA cite statistics in which the number needed to treat represents benefit for only the gross minority of patients.

That said, in the ED and in medicine in general, we provide many treatments in which only a small handful are expected to realize substantial benefit. We must treat 10 to 15 patients complaining of sore throat with dexamethasone for one to enjoy a clinically meaningful difference in symptomatic improvement. A similar number of antibiotic exposures would be needed to prevent a single case of recurrence after abscess drainage. The list is virtually endless, but many of these treatments remain commonplace because the costs and harms are considered relatively small.

This is not the case for tPA in acute ischemic stroke. A subset of patients will likely experience some benefit, but there is also known significant risk for intracranial hemorrhage, not to mention the profound financial costs associated with both the acute evaluation and subsequent hospitalization relating to tPA administration. However, the guidelines and certifications forced upon us offer little or no flexibility in narrowing the treatment population. Surprisingly, in 23 years little evidence or guidance has been offered to clarify the individual balance between risks and benefits.

This is where the opportunity for change exists and where ACEP leadership may play an important role. External guidelines affecting ED care must have representation from experts within our specialty to ensure their impact on our practice is not unreasonable. Additional efforts should be made to downgrade evidence produced solely by sponsored entities and to elevate the opinions of those without the voice and platform afforded to those with industry ties. Further, given the pervasiveness of medical reversal for novel treatments and pathways, it would be of great value for our leaders to firmly oppose a perceived standard of care until further independent confirmatory evidence may be accrued.

Our patients may have already lost the battle for additional evidence to help tailor optimal risks and benefits with ischemic stroke. We can, however, help ensure added protections for future innovations by taking a more active but cautious role in the process of translating external guidance to the emergency department.

Dr. Radecki is assistant professor of emergency medicine at The University of Texas Medical School at Houston. He blogs at Emergency Medicine Literature of Note and can be found on Twitter @emlitofnote.

References

1. Kolata G. For many strokes, there’s an effective treatment. Why aren’t some doctors offering it? The New York Times. March 26, 2018, p. D1.
2. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995; 333(24):1581-1587.
3. Prasad V, Vandross A, Toomey C, et al. A decade of reversal: an analysis of 146 contradicted medical practices. Mayo Clin Proc. 2013;88(8):790-798.