The holy grail of tPA proponents, the time-to-revascularization theory, is the subject of this most recent article in JAMA. This is a data mining exercise from the Get With The Guidelines-Stroke Registry – and, actually, there’s not a lot to say. They evaluate 55,000 patients from the registry, and there are significant differences between the cohorts receiving tPA between 0-90, 91-180, and 181-270 minutes – so all their outcomes are dependent on multiple statistical adjustments.
And, when I say multiple, I mean overwhelming:
The variables used in the risk models were patient-level and hospital-level risk adjustors that were expected to be predictive of outcome, based on empirical analysis, prior literature, and clinical judgment.
Patient-level factors included age, race/ethnicity, sex, medical history (including atrial fibrillation, prosthetic heart valve, previous stroke or TIA, coronary heart disease or prior myocardial infarction, carotid stenosis, peripheral vascular disease, hypertension, dyslipidemia, diabetes, and current smoking), stroke severity (NIHSS), an age-by-NIHSS interaction term, arrival time during regular work hours (7 AM-PM Monday-Friday), arrival mode (ambulance, private vehicle), and select classes of vascular risk prevention medications prior to admission.
Hospital-level factors included hospital size, region, teaching status, rural location, certified primary stroke center status, average number of patients treated with tPA annually, and average number of annual stroke dis- charges. All variables were included in the predictive models without use of a stepwise or other formal variable selection process.
The pharmaceutical industry conflict-of-interest disclosure is even longer.
These folks could have made these data say whatever they desired with their statistical weighting. They report a positive association with time-to-treatment and improved outcomes; the astute reader may interpret this as they are wont.
It is also worth mentioning the earlier time-to-treatment populations are probably more likely to include stroke mimics and TIAs – both of which tend towards excellent outcomes, with or without tPA. The percentage of stroke mimics treated with tPA ranges between 6.5% and 15.5% at academic centers using MRI as imaging confirmation, and has been estimated to be as high as 25% to 29% in community settings. The GWTG-Stroke registry specifically fails to account for stroke mimics in their coding instructions – a patient that receives tPA and rapidly improves is to be coded as “aborted stroke”, even though contemporary evidence throws this concept into doubt.
Regardless, the percentage of stroke mimics confounding the results likely dwarfs the magnitude of effect of the proposed time-to-treatment association reported by these authors.
“Time to Treatment With Intravenous Tissue Plasminogen Activator and Outcome From Acute Ischemic Stroke”