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Non-vitamin K antagonist oral anticoagulants with amiodarone, P-glycoprotein inhibitors, or polypharmacy in patients with atrial fibrillation: Systematic review and meta-analysis

Authors
 In-Soo Kim MD a  ;  Hyun-Jung Kim MPH  ;  PhD b  ;  Hee Tae Yu MD  ;  PhD a  ;  Tae-Hoon Kim MD a  ;  Jae-Sun Uhm MD  ;  PhD a  ;  Jong-Youn Kim MD  ;  PhD a  ;  Boyoung Joung MD  ;  PhD a  ;  Moon-Hyoung Lee MD  ;  PhD a  ;  Hui-Nam Pak MD  ;  PhD 
Citation
 JOURNAL OF CARDIOLOGY, Vol.73(6) : 515-521, 2019 
Journal Title
 JOURNAL OF CARDIOLOGY 
ISSN
 0914-5087 
Issue Date
2019
Keywords
Amiodarone ; Atrial fibrillation ; Meta-analysis ; Non-vitamin K antagonist oral anticoagulants ; Polypharmacy
Abstract
BACKGROUND: Amiodarone, which inhibits CYP2C9 and P-glycoprotein, is commonly prescribed with non-vitamin K antagonist oral anticoagulants (NOACs) and polypharmacy in high-risk atrial fibrillation (AF) patients. We studied efficacy and safety of NOACs in AF patients receiving amiodarone, P-glycoprotein inhibitor, or polypharmacy. METHODS: After a systematic database search (Medline, EMBASE, CENTRAL, SCOPUS, and Web of Science), four phase-III randomized trials comparing NOACs and warfarin in "with/without amiodarone," "with/without P-glycoprotein inhibitors," or "with/without multiple (≥5, polypharmacy) concomitant drugs" subgroups were included. The outcomes were pooled using a random-effects model to determine the relative risks (RRs) for stroke/systemic thromboembolism (SSTE), major bleeding (MB), intracranial hemorrhage (ICH), and all-cause mortality. RESULTS: Among patients taking amiodarone, superiority of NOACs over warfarin in non-amiodarone users disappeared in terms of SSTE (p=0.11), MB (p=0.95), ICH (p=0.26), and mortality (p=0.32). No safety benefit (MB) of NOACs compared to warfarin was shown in patients taking P-glycoprotein inhibitors (p=0.47), but SSTE prevention was still superior with NOACs compared to warfarin in the same patient group [RR=0.78 (0.61-0.99), p=0.04, I2=11%]. In AF patients with polypharmacy, NOACs showed a lower risk of SSTE [RR=0.82 (0.71-0.96), p=0.01, I2=0%] and mortality [RR=0.91 (0.83-0.99), p=0.04, I2=0%], but not MB (p=0.81) compared to warfarin. CONCLUSIONS: NOACs were equivalent to warfarin among AF patients with concomitant amiodarone use in terms of efficacy, safety, and mortality. There was no safety benefit of NOACs over warfarin in patients using polypharmacy or P-glycoprotein inhibitors. SYSTEMATIC REVIEW REGISTRATION: The protocol of this meta-analysis was registered on PROSPERO under CRD42018104808 (https://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42018104808).
Full Text
https://www.sciencedirect.com/science/article/pii/S0914508719300012
DOI
10.1016/j.jjcc.2018.12.018
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, In-Soo(김인수) ORCID logo https://orcid.org/0000-0003-2801-5514
Kim, Jong Youn(김종윤) ORCID logo https://orcid.org/0000-0001-7040-8771
Kim, Tae-Hoon(김태훈) ORCID logo https://orcid.org/0000-0003-4200-3456
Pak, Hui Nam(박희남) ORCID logo https://orcid.org/0000-0002-3256-3620
Uhm, Jae Sun(엄재선) ORCID logo https://orcid.org/0000-0002-1611-8172
Yu, Hee Tae(유희태) ORCID logo https://orcid.org/0000-0002-6835-4759
Lee, Moon Hyoung(이문형) ORCID logo https://orcid.org/0000-0002-7268-0741
Joung, Bo Young(정보영) ORCID logo https://orcid.org/0000-0001-9036-7225
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/169976
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