Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Original Paper Cerebrovasc Dis 2013;35:45–52 DOI: 10.1159/000345071 Renal Impairment Reduces the Efficacy of Thrombolytic Therapy in Acute Ischemic Stroke Albert Power a Daniel Epstein b David Cohen c Raj Bathula c Joe Devine c Arindam Kar b David Taube a Neill Duncan a Diane Ames b a Imperial Renal and Transplant Center and b Imperial Hyperacute Stroke Unit, Imperial College Healthcare NHS Trust, and c Northwick Park Hyperacute Stroke Unit, North West London Hospitals NHS Trust, London, UK to determine the association between demographic charac- teristics and comorbid factors of interest and outcomes. eGFR was calculated using the Chronic Kidney Disease Epi- demiology Collaboration equation. Results: There was no significant difference in mean time to thrombolysis between the groups (221 8 66 vs. 220 8 70 min from symptom onset; p = 0.9). An eGFR !60 ml/min was independently associated with a statistically significant reduction of the therapeutic effect of alteplase at 24 h on multivariate regression [coeffi- cient –2.3, 95% confidence interval (CI) –3.7 to –0.9; p = 0.002], and this persisted at 7 days (coefficient –3.5, 95% CI –5.3 to –1.7; p ! 0.001). On modeling eGFR as a continuous variable, every 10 ml/min decline in eGFR was associated with a 0.40 diminution in NIHSS score improvement with al- teplase (95% CI 0.07–0.74; p = 0.02). Older age and a higher presenting NIHSS score were associated with a greater ther- apeutic effect (p = 0.04 and p ! 0.001, respectively). In-pa- tient mortality was 5%, with no significant differences be- tween groups. Renal impairment was not associated with a higher rate of ICH (6.2 vs. 6.7%; p = 0.9). Greater NIHSS score at presentation was the only factor associated with a greater risk of death (odds ratio 1.24, 95% CI 1.10–1.40; p ! 0.001) and ICH (odds ratio 1.12, 95% CI 1.03–1.23; p = 0.004). Conclu- sions: Our results suggest that renal impairment is associ- ated with reduced efficacy of thrombolysis in acute ischemic Key Words Alteplase  Renal impairment  Stroke  Thrombolysis Abstract Background: Renal impairment is a potent risk factor for stroke, which remains a leading cause of death and disability. Thrombolysis for acute ischemic stroke has transformed pa- tient outcomes, although the safety and efficacy of this ap- proach remain poorly characterized in patients with renal dysfunction, who manifest a higher risk of bleeding due to uremia. We therefore examined the impact of renal impair- ment on clinical outcomes with thrombolysis within the cur- rent 4.5-hour therapeutic window. Methods: This retro- spective multicenter cohort study (2009–2011) examined 229 stroke patients receiving thrombolysis with alteplase (0.9 mg/kg; mean age 70 8 13 years; 59% male, 24% diabet- ic). Sixty-five patients had an estimated glomerular filtration rate (eGFR) !60 ml/min. The primary outcome was the im- provement in National Institutes of Health Stroke Scale (NIHSS) score at 24 h. Secondary outcomes included the NIHSS score at 7 days, the incidence of symptomatic and as- ymptomatic intracranial hemorrhage (ICH), extracranial bleeding and death during the index hospitalization. Uni- variate and multivariate regression analyses were performed Received: August 17, 2012 Accepted: October 11, 2012 Published online: February 14, 2013 Dr. Albert Power, MD Imperial Renal and Transplant Center, Imperial College Healthcare NHS Trust 4th Floor, Hammersmith House, Hammersmith Hospital, DuCane Road London W12 0HS (UK) E-Mail albert.power  @  nhs.net © 2013 S. Karger AG, Basel 1015–9770/13/0351–0045$38.00/0 Accessible online at: www.karger.com/ced Downloaded by: 198.143.37.97 - 3/31/2016 1:32:58 AM