Alteplase Dose for Ischemic Stroke in Very Heavy Patients

As obesity becomes more prevalent, patients who present with acute ischemic stroke are increasingly likely to be obese. Intravenous (IV) recombinant tissue plasminogen activator (r-tPA), the only FDA-approved drug for ischemic stroke, can be given at a maximum dose of 90 mg. Therefore, r-tPA recipients who weigh more than 100 kg get a lower per-kilogram dose than lighter patients. Furthermore, obese people tend to have elevated levels of plasminogen activator inhibitor-1, a major endogenous inhibitor of tPA.

To learn more about the effectiveness of r-tPA treatment in patients who weigh >100 kg, researchers analyzed prospective data on IV alteplase in 27,910 ischemic-stroke patients who had entered a large, international thrombolysis registry from late 2002 to late 2009. About 15% of the patients were weighed; estimates were used for the rest. In all, 4.3% of the registrants weighed >100 kg. Compared with lighter patients, these heavier patients received a significantly lower per-kilogram alteplase dose (mean, 0.82 vs. 0.90 mg/kg), were significantly younger (mean age, 62 vs. 70), and had significantly less-severe strokes — but were also more likely to have vascular risk factors.

The rate of major neurological improvement (MNI) at 24 hours after treatment, an index of successful recanalization, was 28% in both groups. The rate of symptomatic intracerebral hemorrhage (SICH), according to 22- to 36-hour posttreatment brain imaging, was significantly higher in the heavier group than in the lighter group (2.6% vs. 1.7%). After adjustment for baseline differences, the two groups did not differ significantly in MNI at 24 hours or functional independence at 3 months. Compared with the lighter group, the heavier group had significantly higher risks for SICH (odds ratio, 1.60) and mortality at 3 months (OR, 1.37).