Is the maximum dose of 90 mg alteplase sufficient for patients with ischemic stroke weighing >100 kg?

Background and Purpose—Intravenous alteplase for acute ischemic stroke has a maximum dose limit of 90 mg. Consequently, patients 100 kg body weight receive a lower per-kilogram dose compared with those 100 kg. We investigated if the lower per-kilogram dose is associated with poor early neurological improvement and worse outcome after thrombolysis. Methods—Of 27 910 patients registered in Safe Implementation of Treatment in Stroke–International Stroke Thrombolysis Register (SITS-ISTR; 2002 to 2009), 1190 (4.3%) weighed 100 kg. Major neurological improvement was used to estimate recanalization (National Institutes of Health Stroke Scale improvement 8 points or score of 0 at 24 hours). Outcome measures included symptomatic intracerebral hemorrhage (National Institutes of Health Stroke Scale deterioration 4 points within 24 hours and Type 2 parenchymal hemorrhage), functional independence (modified Rankin Scale 0 to 2), and mortality at 3 months. Results—Patients 100 kg received a lower per-kilogram alteplase dose (0.82 versus 0.90, P0.001), were younger (62 versus 70 years, P0.001), had a lower baseline National Institutes of Health Stroke Scale (10 versus 12, P0.001), but more frequently had cardiovascular risk factors. Major neurological improvement at 24 hours occurred in 27.7% in both groups. Symptomatic intracerebral hemorrhage occurred in 2.6% versus 1.7% (P0.03) in 100 kg versus 100 kg. Functional independence was 59.7% versus 53.6% (P0.001) and mortality was 14.4% versus 15.1% (P0.54). After adjustment for baseline characteristics, there was no significant difference for major neurological improvement or functional independence between 100 kg and 100 kg, but 100-kg patients had a higher odds ratio for symptomatic intracerebral hemorrhage (OR, 1.6; 95% CI, 1.06 to 2.41; P0.02) and mortality (OR, 1.37; 95% CI, 1.08 to 1.74; P0.01). Conclusions—Our results support the current upper dose limit. There was a higher incidence of symptomatic intracerebral hemorrhage in patients 100 kg despite the lower per-kilogram recombinant tissue plasminogen activator dose. Major neurological improvement and functional independence were similar.