APOE4 May Raise Brain Bleed Risk in Apixaban Users With AF

METHODOLOGY:

The study included data for more than 2000 participants (mean age, 71 years; 55% men; 84% with European ancestry) from the All of Us Research Program, collected between 2017 and 2022. The median follow-up duration was 2.9 years.
Individuals older than 50 years who were taking apixaban for AF were included in the study, which excluded those with prior ischemic stroke or ICH.
After APOE ε4 status was determined, carriers (n = 483) were defined as those having one or two alleles and noncarriers (n = 1555) as those without alleles.
The primary outcome was incident ICH after initiating apixaban therapy, including any nontraumatic intraparenchymal, subdural, or subarachnoid hemorrhage. Secondary outcomes included incidences of intraparenchymal hemorrhage, ischemic stroke, and a composite of ischemic stroke and ICH. Also used was a HAS-BLED score, which includes factors such as age, hypertension, stroke, and history of or predisposition for bleeding, to predict risk for major bleeding.

About 26 participants developed ICH during the study, with cumulative ICH incidence significantly higher among APOE ε4 carriers than noncarriers (3.1% vs 1%; P = .007).
Carrying the APOE ε4 allele was associated with a threefold increase in risk for ICH (hazard ratio [HR], 3.1; P = .004) and intraparenchymal hemorrhage (HR, 3.7; P = .002) compared with not carrying the allele.
There were no significant differences between carriers and noncarriers in the other two secondary outcomes.
APOE information improved the predictive power of the HAS-BLED score, with C statistics of 0.74 and 0.68 for models with and without APOE information, respectively (P = .03).

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