Patient-Reported Quality of Life After Intravenous Alteplase for Stroke in the WAKE-UP Trial

BACKGROUND AND OBJECTIVES: Intravenous alteplase improves functional outcome after acute ischemic stroke. However, little is known about the effects on self-reported health-related quality of life (HRQoL). METHODS: WAKE-UP was a multicenter, randomized, placebo-controlled trial of MRI-guided intravenous alteplase in stroke with unknown onset time. HRQoL was assessed using the EQ-5D questionnaire at 90 days, comprising the EQ-5D index and the EQ visual analogue scale (VAS). Functional outcome was assessed by the modified Rankin Scale (mRS). We calculated the effect of treatment on EQ-5D index and EQ VAS using multiple linear regression models. Mediation analysis was performed on stroke survivors to explore the extent to which the effect of alteplase on HRQoL was mediated by functional outcome. RESULTS: Among 490 stroke survivors, the EQ-5D index was available for 452 (92.2%), of whom 226 (50%) were assigned to treatment with alteplase and 226 (50%) to placebo. At 90 days, mean EQ-5D index was higher, reflecting a better health state, in patients randomized to treatment with alteplase than with placebo (0.75 vs. 0.67) with an adjusted mean difference of 0.07 (95% CI 0.02-0.12, P=0.005). Also mean EQ VAS was higher with alteplase than with placebo (72.6 vs. 64.9), with an adjusted mean difference of 7.6 (95% CI 3.9-11.8, P\textless0.001). 85% of the total treatment effect of alteplase on the EQ-5D index was mediated via the mRS score, while there was no significant direct effect. In contrast, the treatment effect on the EQ VAS was mainly via the direct pathway (60%), whereas 40% was mediated by the mRS. DISCUSSION: Assessment of patient-reported outcome measures reveals a potential benefit of intravenous alteplase for HRQoL beyond improvement of functional outcome.Trial registration information: ClinicalTrials.gov number, NCT01525290; EudraCT number, 2011-005906-32