One could assume an altruistic interest in patients as the motivating factor behind the expanded use of tPA. However, the underlying funding for much of the work cited by these authors comes from Genentech, whose stroke symposia are fixtures at annual meetings. The pervasive use of tPA, embedded in guidelines, quality measures, and reinforced by statements about the “standard of care,” directly benefits its bottom line. Few statistics are available on the annual revenue derived from tPA since Genentech was purchased by Roche, but thrombolytics accounted for approximately $250 million in sales in 2008. Since then, Genentech has more than doubled the cost of alteplase from approximately $30/mg to more than $60/mg and, as these articles demonstrate, redoubled its efforts to expand indications.⁵

The original NINDS trials enrolled a few hundred patients each. Other rigorous trials, each with their own flaws and conflicts of interest, enrolled similar numbers. Now, 20 years later, rather than prove the safety and effectiveness of tPA for these expanded indications, these recommendations selectively overstate the quality of supporting evidence or simply use the absence of evidence to the contrary as justification.

It is frankly impossible to estimate any of the magnitudes of benefit or harms from the practices endorsed by this new guideline, but it is safe to assume the purported current benefit of tPA is certainly the ceiling. Likewise, as the original contraindications were intended to improve the safety margin of tPA, the anticipated harms must be greater. This is not the sort of work that improves the lives of our patients. We do not need to expand the use of tPA; rather, we ought to be pursuing research that helps us narrow the treatment cohort to those with the stroke syndromes and comorbidities with the ideal risk/benefit profile.

References

1. Brown MD, Burton JH, Nazarian DJ, et al. Clinical policy: use of intravenous tissue plasminogen activator for the management of acute ischemic stroke in the emergency department. Ann Emerg Med. 2015;66(3):322-333.e31.
2. Demaerschalk BM, Kleindorfer DO, Adeoye OM, et al. Scientific rationale for the inclusion and exclusion criteria for intravenous alteplase in acute ischemic stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2016;47(2):581-641.
3. A study of the efficacy and safety of Activase (alteplase) in patients with mild stroke (PRISMS). Accessed Feb. 28, 2016.
4. Levine SR, Khatri P, Broderick JP, et al. Review, historical context, and clarifications of the NINDS rt-PA stroke trials exclusion criteria: part 1: rapidly improving stroke symptoms. Stroke. 2013;44(9):2500-2505.
5. Kleindorfer D, Broderick JP, Demaershalk BM, et al. The cost of alteplase has more than doubled over the past decade. Stroke. 2016;47:AWP78.