title: Impact of Tissue Plasminogen Activator Dosing on Patients Weighing More Than 100 kg on 3-Month Outcomes in Acute Ischemic Stroke.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Pharmacy, West Virginia University Medicine, Morgantown, WV.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Garavaglia
authors.affiliation: Department of Neurology, West Virginia University, Morgantown, WV.
authors.forename: Jay
authors.initials: J
authors.lastname: Sherman
authors.affiliation: Department of Neurology, West Virginia University, Morgantown, WV.
authors.forename: Hannah
authors.initials: H
authors.lastname: Yetzer
authors.affiliation: Department of Biostatistics, West Virginia University, Morgantown, WV.
authors.forename: Michael
authors.initials: M
authors.lastname: Regier
authors.affiliation: Department of Neurology, West Virginia University, Morgantown, WV. Electronic address: mssmith@hsc.wvu.edu.
authors.forename: Matthew
authors.initials: M
authors.lastname: Smith
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001835:Body Weight; D002545:Brain Ischemia / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology; D004185:Disability Evaluation; D054796:Drug Dosage Calculations; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000175:diagnosis / Q000453:epidemiology / Q000503:physiopathology*; D016017:Odds Ratio; D020127:Recovery of Function; D012189:Retrospective Studies; D020521:Stroke / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology; D015912:Thrombolytic Therapy / Q000009:adverse effects / Q000379:methods*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D014903:West Virginia / Q000453:epidemiology; D055815:Young Adult
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator
keywords: Infarction; clinical trials observational; obesity; outcomes research; thrombolysis