Does body weight influence the response to intravenous tissue plasminogen activator in stroke patients?
BACKGROUND
The recommended dose of IV tissue plasminogen activator (t-PA) for ischemic stroke patients weighing >100 kg (ISPW >100 kg) is fixed at 90 mg. Elevated levels of plasminogen activator inhibitor-1 (PAI-1) and impaired fibrinolysis have been reported in heavy patients, suggesting that ISPW >100 kg may require higher doses of t-PA. We hypothesized that ISPW >100 kg are less likely to benefit from IV t-PA compared to patients who weigh <or=100 kg and receive a weight-based dose.


METHODS
We queried the National Institute of Neurological Disorders and Stroke t-PA study database, and performed multivariate logistic regression analyses to analyze the effects of weight (>100 vs. <or=100 kg) and t-PA dose on functional outcomes at 3 months.


RESULTS
Six percent of the t-PA and 10% of the placebo cohorts had an actual body weight >100 kg. Weight >100 kg emerged as a predictor of worse outcome (OR = 5.76; p = 0.017) and neurological deterioration (OR = 3.4; p = 0.07) after t-PA. This negative impact of body weight on outcome was not seen among placebo-treated patients. We also found a trend for an association between lower doses of t-PA and unfavorable 3-month outcomes in t-PA-treated patients (OR = 1.9; p = 0.05).


CONCLUSIONS
ISPW >100 kg seem to derive less benefit from IV t-PA than their lighter counterparts. This may be partly attributed to the use of fixed non-weight-adjusted dosing in heavier patients. The mechanism(s) underlying this observation and its potential therapeutic implications require further investigations.
Lou
Min
M
The 2nd Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China.
Selim
Magdy
M
D000368:Aged; D001835:Body Weight / Q000502:physiology*; D002545:Brain Ischemia / Q000150:complications; D015331:Cohort Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020521:Stroke / Q000188:drug therapy* / Q000209:etiology; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D016896:Treatment Outcome
D010959:Tissue Plasminogen Activator