J Clin Med. 2019;8(10):jcm8101624.

Non-Vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation and Valvular Heart Disease.

, , , , , , , ,

제1저자 문인기, 이소령 · 교신저자 최의근

PMID 31590290 PMC6832302 DOI 10.3390/jcm8101624 IF 3.3 순환기내과

소속 (5)

Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, Korea.
Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, Korea. choiek17@snu.ac.kr.
Department of Medical Statistics, College of Medicine, Catholic University of Korea, Seoul 06591, Korea.
Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Chest & Heart Hospital, Liverpool, UK.
Department of Clinical Medicine, Aalborg University, 9000 Aalborg, Denmark.

Abstract

BACKGROUND There are limited data for non-vitamin K antagonist oral anticoagulants (NOACs) impact on outcomes for patients with atrial fibrillation (AF) and valvular heart diseases (VHDs).

METHODS We identified patients with AF and associated Evaluated Heartvalves, Rheumatic or Artificial (EHRA) type 2 VHDs, and who had been naïve from the oral anticoagulants in the Korean National Health Insurance Service database between 2014 and 2016 (warfarin: n = 2671; NOAC: n = 3058). For analyzing the effect of NOAC on primary prevention, we excluded those with a previous history of ischemic stroke, intracranial hemorrhage (ICH), and gastrointestinal (GI) bleeding events. To balance covariates, we used the propensity score weighting method. Ischemic stroke, ICH, GI bleeding, major bleeding, all-cause death, and their composite outcome and fatal clinical events were evaluated.

RESULTS During a follow-up with a mean duration of 1.4 years, NOACs were associated with lower risks of ischemic stroke (hazard ratio (HR): 0.71, 95% confidence interval (CI): 0.53-0.96), GI bleeding (HR: 0.50, 95% CI: 0.35-0.72), fatal ICH (HR: 0.28, 95% CI: 0.07-0.83), and major bleeding (HR: 0.61, 95% CI: 0.45-0.80) compared with warfarin. Overall, NOACs were associated with a lower risk of the composite outcome (HR: 0.68, 95% CI: 0.58-0.80).

CONCLUSIONS In this nationwide Asian AF population with EHRA type 2 VHDs, NOAC use was associated with lower risks of ischemic stroke, major bleeding, all-cause death, and the composite outcome compared to warfarin use.

Keywords

atrial fibrillationbleedingnon-vitamin K antagonist oral anticoagulantstrokevalvular heart disease

Figures

**Figure 1** Study population enrollment flow. A total of 5729 patients with EHRA type 2 VHDs were included in the final analysis. We conducted an exploratory analysis for EHRA type 1 VHD patients (patients with “valvular AF”) (n = 611). Abbreviations: AF, atrial fibrillation; EHRA, Evaluated Heartvalves, Rheumatic or Artificial; ESRD, end-stage renal disease; GI, gastrointestinal; NOAC, non-vitamin K antagonist oral anticoagulant; OAC, oral anticoagulant, VHD, valvular heart disease.

**Figure 2** Weighted cumulative incidence curves of 6 clinical outcomes of NOAC versus warfarin. Compared to warfarin, NOACs showed significantly lower incidence rates of ischemic stroke, GI bleeding, major bleeding, and all-cause mortality. NOAC and warfarin groups showed similar incidence rates of intracranial hemorrhage (ICH). Overall, NOACs were associated with a lower rate of the composite outcome. Abbreviations: GI, gastrointestinal; NOAC, non-vitamin K antagonist oral anticoagulant; WFR, warfarin.

**Figure 3** Weighted event numbers, incidence rates, and HRs of 6 clinical outcomes and fatal events in NOAC versus warfarin (reference) in patients with EHRA type 2 VHDs: (A) HRs of 6 clinical outcomes; (B) HRs of fatal clinical events. Compared to warfarin, NOACs were associated with lower risks of ischemic stroke, GI bleeding, and major bleeding. Although NOAC and warfarin groups showed similar incidence rates of ICH, the NOAC group was associated with a significantly lower risk of fatal ICH compared to warfarin group. Overall, NOACs were associated with a lower risk of the composite outcome (HR: 0.68, 95% CI: 0.58–0.80). Abbreviations: CI, confidence interval; GI, gastrointestinal; HR, hazard ratio; ICH, intracranial hemorrhage; NOAC, non-vitamin K antagonist oral anticoagulant.

**Figure 4** HRs of ischemic stroke, intracranial hemorrhage, all-cause death, GI bleeding, major bleeding, and composite outcome according to various subgroups in NOAC and warfarin (reference). * P for interaction; ^† Other valvular disease included AS, AR, TS, TR, PS, and PR. Abbreviations: AR, aortic regurgitation; AS, aortic stenosis; CI, confidence interval; GI, gastrointestinal; HR, hazard ratio; MR, mitral regurgitation; NOAC, non-vitamin K antagonist oral anticoagulant, PR, pulmonary regurgitation; PS, pulmonary stenosis; TR, tricuspid regurgitation; TS, tricuspid stenosis; VHD, valvular heart disease.

**Figure 5** Event numbers, crude incidence rates, and HRs of six clinical outcomes with pooled NOAC versus warfarin (reference) using multivariate Cox regression analysis in patients with EHRA type 1 VHDs. The NOAC group showed a comparable risk of ischemic stroke, ICH, all-cause death, and composite outcome. In hospitalization for GI bleeding and major bleeding, NOAC use was associated with a significantly lower risk compared to the use of warfarin. Abbreviations: CI, confidence interval; EHRA, Evaluated Heartvalves, Rheumatic or Artificial; GI, gastrointestinal; HR, hazard ratio; ICH, intracranial hemorrhage; NOAC, non-vitamin K antagonist oral anticoagulant.

그림 출처: PubMed Central 공개 논문 (PMC6832302)

Conflict of interest statement

G.Y.H.L. is a consultant for Bayer/Janssen, BMS/Pfizer, Medtronic, Boehringer Ingelheim, Novartis, Verseon and Daiichi-Sankyo, and a speaker for Bayer, BMS/Pfizer, Medtronic, Boehringer Ingelheim, and Daiichi-Sankyo. No fees are received personally. E.-K.C. received a research grant from Daiichi-Sankyo, BMS/Pfizer, and Biosense Webster.

그 밖의 정보