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. 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. 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).
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.
Does body weight influence the response to intravenous tissue plasminogen activator in stroke patients?