OC 53.3 - Effect of genetic variants on bleeding with rivaroxaban in pulmonary embolism patients: A multicenter prospective cohort study

Tuesday, June 25, 2024

10:00 – 10:15 ICT

Room: Ballroom B3

Presenting Author(s)

Haobo Li

PhD student
China-Japan Friendship Hospital
Beijing, Beijing, China (People's Republic)

Co-Author(s)

ZZ

Zhu Zhang

attending physician
China-Japan Friendship Hospital
Beijin, Beijing, China (People's Republic)
Linfeng Xi, MD

resident physician
China-Japan Friendship Hospital
Beijing, Beijing, China (People's Republic)
Yu Zhang, MD

fellow
China-Japan Friendship Hospital
Beijing, Beijing, China (People's Republic)
HW

Haoyi Weng

professor
Central South University
Changsha, Hunan, China (People's Republic)
XZ

Xianbo Zuo

professor
China-Japan Friendship Hospital
Beijing, Beijing, China (People's Republic)
Zhenguo Zhai, MD,PhD

professor
China-Japan Friendship Hospital, Beijing, China; National Clinical Research Center for Respiratory Diseases, Beijing, China
Beijing, Beijing, China (People's Republic)
CW

Chen Wang

President of Chinese Academy of Medical Sciences & Peking Union Medical College
Chinese Academy of Medical Sciences & Peking Union Medical College
Beijing, Beijing, China (People's Republic)

Background: The genetic feature is a critical factor for the efficacy and safety of rivaroxaban by affecting plasma concentration during extended treatment of pulmonary embolism (PE). However, the existing bleeding risk scores did not include genetic variants.

Aims: This study aimed to explore whether incorporating genetic factors in current model improved the accuracy.

Methods: Patients with PE receiving therapeutic doses of rivaroxaban were enrolled. The primary outcome, bleeding events, was monitored over a one-year follow-up period. A genome-wide association study and candidate gene association analyses were conducted. Genetic variants were integrated into four established clinical bleeding risk scores to develop combined clinical-genetic risk assessments. The predictive accuracy of these scores was evaluated using the area under the receiver operating characteristic curve (AUC).

Results: This study included 3,498 patients treated with rivaroxaban. The bleeding rate during extended treatment was 4.3%. Identified risk factors for bleeding included stroke, abnormal liver function, and hypertension. In 510 patients underwent genotyping, one single-nucleotide polymorphism (SNP) ABLIM2 rs6819260 was significantly related to bleeding (odds ratio [OR] = 8.91, 95% confidence interval [CI]: 4.08–19.47, p = 4.22 × 10−8). Incorporating ABLIM2 rs6819260 into existing risk models significantly improved the AUC by more than 10.0%.

Conclusion(s): Genetic variations significantly influence bleeding risk in Chinese PE patients treated with rivaroxaban during extended anticoagulation. Integrating the ABLIM2 rs6819260 SNP into bleeding risk models substantially enhances their predictive accuracy and facilitates the use of these models to guide individualized treatment decisions in clinical practice.