Is the Maximum Dose of 90 mg Alteplase Sufficient for Patients With Ischemic Stroke Weighing >100 kg?

Abstract

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, P <0.001), were younger (62 versus 70 years, P <0.001), had a lower baseline National Institutes of Health Stroke Scale (10 versus 12, P <0.001), 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% ( P =0.03) in >100 kg versus ≤100 kg. Functional independence was 59.7% versus 53.6% ( P <0.001) and mortality was 14.4% versus 15.1% ( P =0.54). 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; P =0.02) and mortality (OR, 1.37; 95% CI, 1.08 to 1.74; P =0.01). 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.