Impact of Tissue Plasminogen Activator Dosing on Patients Weighing More Than 100 kg on 3-Month Outcomes in Acute Ischemic Stroke

Background and Purpose The landmark National Institute of Neurological Disorders and Stroke (NINDS) tissue plasminogen activator (tPA) trial established the effectiveness and dosing of intravenous tPA for acute ischemic stroke (AIS) at .9 mg/kg with a maximum dose of 90 mg. Since the publication of the NINDS trial in 1995, there has been a drastic increase in the amount of obesity and the average weight of adults in the United States, which has caused an increase in the number of patients receiving 90 mg of alteplase for AIS. This retrospective trial was an attempt to see if reduced-dose tPA is as effective as full .9 mg/kg dosing. Methods We performed a single-center retrospective analysis to assess the dosing rate and 90-day outcomes comparing maximum dosage (90 mg) and standard dosage (.9 mg/kg) of tPA. Results A total of 301 patients were included in the analysis with 64 (21%) receiving less than .9 mg/kg dosing. The adjusted binary logistic regression model showed a statistically significant association toward a good outcome for increases in tPA dose rate (odds ratio = 1.7, P = .027) when compared against a poor outcome. Our analysis showed that patients receiving doses of alteplase closer to .9 mg/kg had a higher likelihood of a modified Rankin Scale score of 0-1 at 90 days. Conclusions With the growth of obesity in the United States and the lack of data supporting dose capping of alteplase, it remains unclear if this dosing practice should continue to be accepted without question. Further studies are needed to assess optimum dosing practices particularly given the obesity epidemic.