Background and Purpose: As lower doses of alteplase reduce the risk of symptomatic intracerebral hemorrhage (sICH), older and Asian people may benefit more from low-dose alteplase than other patients with acute ischemic stroke (AIS).
Methods: Data from the ENhanced Control of Hypertension ANd Thrombolysis strokE study (ENCHANTED), an international, multi-center, prospective, randomized, open-label, blinded-endpoint trial, were analyzed to assess effects of low- (0.6mg/kg body weight) vs. standard-dose (0.9mg/kg) alteplase in AIS patients, by age and ethnicity (Asian vs. non-Asian), pre-specified subgroup analyses, on key efficacy and safety outcomes.
Results: 3297 patients (1248 female), mean age 67 years were included. After adjusting for baseline characteristics and management variables over the first seven days, increasing age was associated with poor outcome, defined by ordinal analysis of the modified Rankin score (mRS) (shift to a less favorable outcome, P trend <0.0001). In the comparison between low- and standard-dose alteplase, no significant differences were observed for 90-day poor outcome by age deciles and ethnicity. Less sICH was observed with low-dose alteplase, and this was consistent for age and ethnicity. There was no ethnic difference in the treatment effects by age, severity, and time to treatment.
Conclusions: Increasing age predicts poor outcome in thrombolysis-treated AIS patients. There was no heterogeneity in the treatment effects of low- vs. standard-dose alteplase. Decisions about intravenous thrombolysis should be based on variables other than age and ethnicity.