Genetic variants influenced the risk of bleeding and pharmacodynamics of rivaroxaban in patients with nonvalvular atrial fibrillation : A multicentre prospective cohort study
© 2023 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics..
INTRODUCTION: Individual variability of rivaroxaban was observed in clinical application. This study aimed to identify genetic variants associated with the variability of pharmacodynamics and bleeding risk of rivaroxbaban in patients with nonvalvular atrial fibrillation (NVAF).
MATERIALS AND METHODS: From June 2017, and July 2019, this study enrolled 257 patients with NVAF receiving rivaroxaban. Pharmacodynamics was assessed by determining anti-Factor Xa (anti-FXa) level 3 h after rivaroxaban administration as peak concentration. Whole-exome sequencing was performed to detected single nucleotide polymorphisms (SNPs). This study was registered (NCT03161496).
RESULTS: The bleeding events within 12 months were significantly related to the peak anti-FXa level (p = .027). SUSD3 rs76292544 was associated with 12-month bleeding events (odds ratio [OR]: 4.20, 95% confidence interval [CI]: 2.17-8.14, p = 6.43×10-5 ). Five SNPs including NCMAP rs4553122 (p = 2.29×10-5 ), PRF1 rs885821 (p = 7.02×10-5 ), PRKAG2 rs12703159 (p = 7.97×10-5 ), PRKAG2 rs13224758 (p = 8.70×10-5 ), and POU2F3 rs2298579 (p = 8.24×10-5 ) were associated with peak anti-FXa level. Genetic variants of 52 SNPs from 36 genes including GOT2 rs14221 and MMP13 rs640198 were potentially related to 12-month bleeding events caused by rivaroxaban's efficacy.
CONCLUSIONS: Peak anti-FXa level was associated with risk of bleeding events in patients with NVAF receiving rivaroxaban. SUSD3 rs76292544 was suggestively associated with 12-month bleeding events and five SNPs (NCMAP rs4553122, PRF1 rs885821, PRKAG2 rs12703159, rs13224758 and POU2F3 rs2298579) were suggestively associated with peak anti-FXa level.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
|---|---|
| Enthalten in: |
Clinical and translational medicine - 13(2023), 5 vom: 18. Mai, Seite e1263 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Xiang, Qian [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
9NDF7JZ4M3 |
|---|
| Anmerkungen: |
Date Completed 22.05.2023 Date Revised 31.05.2023 published: Print ClinicalTrials.gov: NCT03161496 Citation Status MEDLINE |
|---|
| doi: |
10.1002/ctm2.1263 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM35705833X |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM35705833X | ||
| 003 | DE-627 | ||
| 005 | 20231226071756.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1002/ctm2.1263 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1190.xml |
| 035 | |a (DE-627)NLM35705833X | ||
| 035 | |a (NLM)37203300 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Xiang, Qian |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Genetic variants influenced the risk of bleeding and pharmacodynamics of rivaroxaban in patients with nonvalvular atrial fibrillation |b A multicentre prospective cohort study |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 22.05.2023 | ||
| 500 | |a Date Revised 31.05.2023 | ||
| 500 | |a published: Print | ||
| 500 | |a ClinicalTrials.gov: NCT03161496 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics. | ||
| 520 | |a INTRODUCTION: Individual variability of rivaroxaban was observed in clinical application. This study aimed to identify genetic variants associated with the variability of pharmacodynamics and bleeding risk of rivaroxbaban in patients with nonvalvular atrial fibrillation (NVAF) | ||
| 520 | |a MATERIALS AND METHODS: From June 2017, and July 2019, this study enrolled 257 patients with NVAF receiving rivaroxaban. Pharmacodynamics was assessed by determining anti-Factor Xa (anti-FXa) level 3 h after rivaroxaban administration as peak concentration. Whole-exome sequencing was performed to detected single nucleotide polymorphisms (SNPs). This study was registered (NCT03161496) | ||
| 520 | |a RESULTS: The bleeding events within 12 months were significantly related to the peak anti-FXa level (p = .027). SUSD3 rs76292544 was associated with 12-month bleeding events (odds ratio [OR]: 4.20, 95% confidence interval [CI]: 2.17-8.14, p = 6.43×10-5 ). Five SNPs including NCMAP rs4553122 (p = 2.29×10-5 ), PRF1 rs885821 (p = 7.02×10-5 ), PRKAG2 rs12703159 (p = 7.97×10-5 ), PRKAG2 rs13224758 (p = 8.70×10-5 ), and POU2F3 rs2298579 (p = 8.24×10-5 ) were associated with peak anti-FXa level. Genetic variants of 52 SNPs from 36 genes including GOT2 rs14221 and MMP13 rs640198 were potentially related to 12-month bleeding events caused by rivaroxaban's efficacy | ||
| 520 | |a CONCLUSIONS: Peak anti-FXa level was associated with risk of bleeding events in patients with NVAF receiving rivaroxaban. SUSD3 rs76292544 was suggestively associated with 12-month bleeding events and five SNPs (NCMAP rs4553122, PRF1 rs885821, PRKAG2 rs12703159, rs13224758 and POU2F3 rs2298579) were suggestively associated with peak anti-FXa level | ||
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a atrial fibrillation | |
| 650 | 4 | |a bleeding | |
| 650 | 4 | |a genetic polymorphism | |
| 650 | 4 | |a pharmacodynamics | |
| 650 | 4 | |a rivaroxaban | |
| 650 | 7 | |a Rivaroxaban |2 NLM | |
| 650 | 7 | |a 9NDF7JZ4M3 |2 NLM | |
| 650 | 7 | |a Factor Xa Inhibitors |2 NLM | |
| 700 | 1 | |a Wang, Zhe |e verfasserin |4 aut | |
| 700 | 1 | |a Mu, Guangyan |e verfasserin |4 aut | |
| 700 | 1 | |a Xie, Qiufen |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Zhiyan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Shuang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Hanxu |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Zining |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Kun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yatong |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Zinan |e verfasserin |4 aut | |
| 700 | 1 | |a Yuan, Dongdong |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Liping |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Tingting |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Jinhua |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Na |e verfasserin |4 aut | |
| 700 | 1 | |a Xiang, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Gu, Zhichun |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Jianjun |e verfasserin |4 aut | |
| 700 | 1 | |a Cui, Yimin |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Clinical and translational medicine |d 2012 |g 13(2023), 5 vom: 18. Mai, Seite e1263 |w (DE-627)NLM224642685 |x 2001-1326 |7 nnns |
| 773 | 1 | 8 | |g volume:13 |g year:2023 |g number:5 |g day:18 |g month:05 |g pages:e1263 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1002/ctm2.1263 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 13 |j 2023 |e 5 |b 18 |c 05 |h e1263 | ||