Influence of renal impairment on outcome for thrombolysis-treated acute ischemic stroke: ENCHANTED post-hoc analysis

Background and purpose: Renal dysfunction (RD) is associated with poor prognosis following stroke. We assessed the effects of RD on outcomes and interaction with low- versus standard-dose alteplase in a post-hoc subgroup analysis of the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). Methods: 3220 thrombolysis-eligible patients with acute ischemic stroke (AIS) (mean age 66.5 years, 37.8% female) were randomly assigned to low-dose (0.6mg/kg) or standard-dose (0.9mg/kg) intravenous alteplase within 4.5 hours of symptom onset. 659 (19.8%) patients had moderate-to-severe RD (estimated glomerular filtration rate [eGFR] <60ml/min/1.73m2) at baseline. The impact of RD on death or disability (modified Rankin scale [mRS] scores 2 to 6) at 90-days, and symptomatic intracerebral hemorrhage (sICH), was assessed in logistic regression models. Results: Compared to patients with normal renal function (>90ml/min/1.73m2), those with severe RD (<30ml/min/1.73m2) had increased mortality (adjusted odds ratio [OR] 2.07, 95% confidence intervals [CI] 0.89-4.82; p=0.04 for trend); every 10ml/min/1.73m2 lower eGFR was associated with an adjusted 9% increased odds of death from thrombolysis-treated AIS. There was no significant association with mRS scores 2-6 (1.03, 0.62-1.70; p=0.81 for trend), mRS 3-6 (1.20, 0.72-2.01; p=0.44 for trend) or sICH, nor any heterogeneity in comparative treatment effects between low-dose and standard-dose alteplase by RD grades. Conclusions: RD is associated with increased mortality but not disability or sICH in thrombolysis-eligible and treated AIS patients. Uncertainty persists as to whether low-dose alteplase confers benefits over standard-dose in AIS patients with RD. Clinical Trial Registration: Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01422616