Apolipoprotein E phenotype and the efficacy of intravenous tissue plasminogen activator in acute ischemic stroke

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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 × 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.