Abstract Details

Title Polygenic Risk Factor Profiling and Risk of Intracerebral Hemorrhage In Patients with Atrial Fibrillation on Apixaban

Topic Cerebrovascular Disease and Interventional Neurology

Presentation(s) P9 - Poster Session 9 (11:45 AM-12:45 PM)

Poster/Presentation
Number 13-008

Objective To evaluate whether a combined polygenic risk factor profile (PRFP) increases the risk of intracranial hemorrhage (ICH) in atrial fibrillation (AF) patients on apixaban.

Background Apixaban is the most widely used anticoagulant in AF patients, and ICH is its most severe adverse effect. Hypertension, diabetes, dyslipidemia, and chronic kidney disease are well-known risk factors for ICH. However, the relationship between their combined PRFP and ICH risk in AF patients on apixaban remains unclear.

Design/Methods We conducted a prospective genetic association study within All of Us, including participants >50y with AF, taking apixaban, and without prior history of ischemic stroke or ICH. PRFP was calculated using five polygenic risk scores (for systolic blood pressure, type 2 diabetes, LDL and HDL, and glomerular filtration rate), as well as APOE epsilon 4 and 2 genotypes, ascertained using variants rs429358 and rs7412. PRFP was categorized into favorable (<20%), neutral (20%-80%), and adverse (>80%) risk. The outcome was incident ICH (intraparenchymal, subdural, or subarachnoid hemorrhage) after apixaban initiation.

Results In 2,088 participants (mean age 71y, 45% female) with 2.9 years of median follow-up, 26 cases of ICH occurred (cumulative incidence: 1.5% [95%CI: 1.00–2.20]). Participants with an adverse PRFP had more than three times the risk of ICH compared to those with a favorable PP (HR: 3.38, 95%CI: 1.09–10.50, p-trend=0.005). Incorporating polygenic information improved the predictive accuracy of clinical scores for ICH, with c-statistics rising from 0.68 to 0.75 (p=0.01).

Conclusions Among AF patients on apixaban, adverse PRFPs for the most important risk factors significantly increase the risk of ICH compared to favorable PRFPs. Additionally, incorporating PRFP data enhances the predictive power of clinical prediction scores for ICH. Future studies should explore whether PRFP can improve clinical decision-making in AF patients.

Authors/Disclosures
Santiago Clocchiatti-Tuozzo (Yale University, Department of Neurology) PRESENTER	Mr. Clocchiatti-Tuozzo has nothing to disclose.
Cyprien Rivier, MD (Yale University)	Dr. Rivier has nothing to disclose.
Shufan Huo, MD, PhD (Yale University)	Dr. Huo has nothing to disclose.
Emily J. Gilmore, MD (Yale University School of Medicine)	Dr. Gilmore has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for carpl.ai. Dr. Gilmore has received personal compensation in the range of $0-$499 for serving as a Consultant for AAN. Dr. Gilmore has received research support from NIH.
Ashkan Shoamanesh, MD	Dr. Shoamanesh has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bayer AG. Dr. Shoamanesh has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Daiichi Sankyo . Dr. Shoamanesh has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Servier Inc.. Dr. Shoamanesh has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurodiem.ca. The institution of Dr. Shoamanesh has received research support from Servier Canada Inc.. The institution of Dr. Shoamanesh has received research support from Daiichi Sankyo Ltd.. The institution of Dr. Shoamanesh has received research support from Bayer AG. The institution of Dr. Shoamanesh has received research support from Bristol-Myers Squibb. The institution of Dr. Shoamanesh has received research support from Octapharma Canada .
Hooman Kamel, MD (Weill Cornell Medical College)	Dr. Kamel has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for JAMA Neurology. Dr. Kamel has received personal compensation in the range of $50,000-$99,999 for serving as a Endpoint adjudication committee with Boehringer-Ingelheim.
Santosh B. Murthy, MD (Weill Cornell Medicine)	Dr. Murthy has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for CarePoint. Dr. Murthy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alnylam. Dr. Murthy has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Stroke and Neurological disorders. The institution of Dr. Murthy has received research support from National Institutes of Health/NINDS.
Lucila Ohno-Machado (Yale University)	No disclosure on file
Kevin N. Sheth, MD, FAAN (Yale UniversityDivision of Neuro and Critical Care)	Dr. Sheth has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ceribell. Dr. Sheth has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Zoll. Dr. Sheth has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for NControl. Dr. Sheth has received stock or an ownership interest from Astrocyte. Dr. Sheth has received stock or an ownership interest from Alva. The institution of Dr. Sheth has received research support from Biogen. The institution of Dr. Sheth has received research support from Novartis. The institution of Dr. Sheth has received research support from Bard. The institution of Dr. Sheth has received research support from Hyperfine. Dr. Sheth has received intellectual property interests from a discovery or technology relating to health care.
Thomas Gill	Thomas Gill has nothing to disclose.
Guido J. Falcone, MD (Yale School of Medicine)	The institution of Dr. Falcone has received research support from NIH. The institution of Dr. Falcone has received research support from AHA.

��ɫ��

��ɫ��