title: Apolipoprotein E phenotype and the efficacy of intravenous tissue plasminogen activator in acute ischemic stroke.
abstract: We used stored plasma samples from 409 patients in the National Institute of Neurological Diseases and Stroke (NINDS) tissue plasminogen activator (t-PA) Stroke Trial to examine the relationship between an apolipoprotein (Apo) E2 or an Apo E4 phenotype and a favorable outcome 3 months after stroke, the risk of intracerebral hemorrhage, and the response to intravenous t-PA therapy. For the 27 patients with an Apo E2 phenotype who were treated with t-PA, the odds ratio (OR) of a favorable outcome at 3 months was 6.4 [95% confidence interval (CI) 2.7-15.3%] compared to the 161 patients without an Apo E2 phenotype who were treated with placebo. The 190 patients treated with t-PA who did not have an Apo E2 phenotype also had a greater, though less pronounced, likelihood of a favorable outcome (OR 2.0, 95% CI 1.2-3.2%) than patients without an Apo E2 phenotype treated with placebo. For the 31 patients with an Apo E2 phenotype treated with placebo, the OR of a favorable 3 month outcome was 0.8 (95% CI 0.4-1.7%) compared to the 161 patients without an Apo E2 phenotype treated with placebo. This interaction between treatment and Apo E2 status persisted after adjustment for baseline variables previously associated with 3 month outcome, for differences in the baseline variables in the two treatment groups and in the Apo E2-positive and -negative groups, and for a previously reported time-to-treatment x treatment interaction (p = 0.03). Apo E4 phenotype, present in 111 (27%) of the 409 patients, was not related to a favorable 3 month outcome, response to t-PA, 3 month mortality, or risk of intracerebral hemorrhage. We conclude that the efficacy of intravenous t-PA in patients with acute ischemic stroke may be enhanced in patients who have an Apo E2 phenotype, whereas the Apo E2 phenotype alone is not associated with a detectable benefit on stroke outcome at 3 months in patients not given t-PA. In contrast to prior studies of head injury and stroke, we could not detect a relationship between Apo E4 phenotype and clinical outcome.
authors.affiliation: Department of Neurology, University of Cincinnati, OH 45267-0525, USA. joseph.broderick@uc.edu
authors.forename: J
authors.initials: J
authors.lastname: Broderick
authors.forename: M
authors.initials: M
authors.lastname: Lu
authors.forename: C
authors.initials: C
authors.lastname: Jackson
authors.forename: A
authors.initials: A
authors.lastname: Pancioli
authors.forename: B C
authors.initials: BC
authors.lastname: Tilley
authors.forename: S C
authors.initials: SC
authors.lastname: Fagan
authors.forename: R
authors.initials: R
authors.lastname: Kothari
authors.forename: S R
authors.initials: SR
authors.lastname: Levine
authors.forename: J R
authors.initials: JR
authors.lastname: Marler
authors.forename: P D
authors.initials: PD
authors.lastname: Lyden
authors.forename: E C
authors.initials: EC
authors.lastname: Haley
authors.forename: T
authors.initials: T
authors.lastname: Brott
authors.forename: J C
authors.initials: JC
authors.lastname: Grotta
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D053329:Apolipoprotein E2; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000097:blood / Q000235:genetics*; D002543:Cerebral Hemorrhage / Q000097:blood / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D016009:Chi-Square Distribution; D004311:Double-Blind Method; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D016017:Odds Ratio; D010641:Phenotype; D010919:Placebos; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D020521:Stroke / Q000097:blood / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D015996:Survival Rate; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000097:blood / Q000627:therapeutic use*; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D053329:Apolipoprotein E2; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D010919:Placebos; D010959:Tissue Plasminogen Activator