NEW YORK (Reuters Health) – In ischemic stroke patients weighing more than 100 kg, the fixed maximum dose limit for intravenous recombinant tissue plasminogen activator (rTPA — alteplase) does not appear to affect outcome, European researchers report in an April 14th online paper in Stroke. But further studies may be needed.

Dr. Niaz Ahmed of Karolinska University Hospital-Solna, Stockholm and colleagues note that European licensing criteria call for rTPA fibrolynitic therapy with a weight-based dose of 0.9 mg/kg and a maximum dose limit of 90 mg. Hence patients weighing more than 100 kg receive a proportionately lower dose than their lighter counterparts.

To examine impact on outcome, the team studied information on almost 28,000 patients, registered between 2002 and 2009, in a worldwide thrombolysis database. In all, 1190 (4.3%) weighed more than 100 kg.

The heavier patients more frequently had cardiovascular risk factors and received a lower rTPA dosage (0.82 versus 0.90 mg). They were also younger (62 versus 70 years) and had a lower baseline National Institutes of Health Stroke Scale level (10 versus 12).

Major neurological improvement at 24 hours was the same (27.7%) in both groups. Functional independence was 59.7% (>100kg) versus 53.6% (?100kg) and mortality was 14.4% versus 15.1%.

After adjustment for baseline characteristics, there was no significant difference in major neurological improvement or functional independence. However the heavier patients had a higher odds ratio for symptomatic intracerebral hemorrhage (1.6) and mortality (1.37).

Given the higher incidence of such hemorrhage and the lack of difference between groups, the researchers conclude that “our results support the current practice of the upper dose limit for rTPA.”

However, Dr. Carlos A. Molina, author of an accompanying editorial, told Reuters Health by email that “These observations are in contrast with a previous study showing that TPA underdosing is associated with poor clinical outcome. The relatively low response and high mortality after thrombolysis in overweight patients is probably associated with their co-morbidity.”

Dr. Molina of Hospital Universitari Vall d’Hebron, Barcelona stressed that “Alteplase has a narrow therapeutic range and, therefore, a strict dosing regimen is required. Efforts should be addressed to avoid standard eyeballing body weight- and TPA dose- estimation.”

He concluded that “A randomized study comparing the 90 mg-dose with the 0.9 mg/kg without higher limit in patients weighing more than 100 kg using arterial recanalization as a direct marker of efficacy is needed.”

Stroke 2011.