There are dueling laments between what could be called “the stroke industrial complex” and the physicians on the front line. Tissue plasminogen activator (tPA) for acute ischemic stroke, in so many words, is repeatedly touted by a handful of guideline-writing experts as simply having “proven benefit.” Their primary lament is the paucity of acute stroke patients receiving tPA. Clinicians on the front line, however, see the perverse incentives wrought by such guidelines and mandates, including the detrimental impact on systems of patient care and costs of prioritizing “quality” targets. Our pragmatic concerns are for the safety of patients and of cautious concern regarding the appropriateness of therapy.
Explore This IssueACEP Now: Vol 35 – No 04 – April 2016
In order to protect our patients, many physicians, and the ACEP Clinical Policy statement, hew closely to the exclusion criteria.1 These exclusion criteria are intended to maximize the safety margin for tPA by minimizing life-threatening intra- and extracranial bleeding. These absolute and relative exclusion criteria are quite conservative and have been under siege for quite some time by the proponents of tPA.
Most recently, the American Heart Association has issued a new update regarding the scientific rationale for inclusion and exclusion criteria for tPA in acute ischemic stroke.2 This document reviews most of the historical exclusions for tPA and makes new recommendations for the use of tPA based on the accumulated evidence. Unsurprisingly, given the conflicts of interest pervasive in the stroke guideline genre, the recommendations are almost universally in favor of giving more tPA. Unfortunately, the authors compound the issue by grossly overstating the strength of the evidence supporting their recommendations.
For example, these authors address the use of tPA in the elderly population. Most trials excluded patients over age 80, and of the 1,711 elderly patients evaluated in clinical trials, 1,617 are from the open-label IST-3 trial. Despite the biases inherent to IST-3, tPA use did not provide a statistically significant favorable outcome at three months. No robust randomized trial data regarding death rates are available, but multiple observational series demonstrate increased risk of intracranial hemorrhage and death in the elderly compared with younger patients receiving tPA. Nonsensically, the authors state “intravenous alteplase administration within three hours is equally recommended for patients less than 80 and more than 80 years of age.” This recommendation, in which limited and conflicting data are presented, is given their strongest Class I recommendation, based on the highest level of evidence.