Original Investigation
Non–Vitamin K Antagonist Oral Anticoagulants in Patients With Atrial Fibrillation and Valvular Heart Disease

https://doi.org/10.1016/j.jacc.2016.12.038Get rights and content
Under a Creative Commons license
open access

Abstract

Background

Valvular heart disease (VHD) and atrial fibrillation (AF) often coexist. Phase III trials comparing non–vitamin K antagonist oral anticoagulants (NOACs) with warfarin excluded patients with moderate/severe mitral stenosis or mechanical heart valves, but variably included patients with other VHD and valve surgeries.

Objectives

This study aimed to determine relative safety and efficacy of NOACs in patients with VHD.

Methods

We performed a meta-analysis of the 4 phase III AF trials of the currently available NOACs versus warfarin in patients with coexisting VHD to assess pooled estimates of relative risk (RR) and 95% confidence intervals (CIs) for stroke/systemic embolic events (SSEE), major bleeding, intracranial hemorrhage (ICH), and all-cause death.

Results

Compared with warfarin, the rate of SSEE in patients treated with higher-dose NOACs was lower and consistent among 13,585 patients with (RR: 0.70; 95% CI: 0.58 to 0.86) or 58,098 without VHD (RR: 0.84; 95% CI: 0.75 to 0.95; interaction p = 0.13). Major bleeding in patients on higher-dose NOACs versus warfarin was similar and consistent among patients with (RR: 0.93; 95% CI: 0.68 to 1.27) or without VHD (RR: 0.85; 95% CI: 0.70 to 1.02; interaction p = 0.63 for VHD/no-VHD difference). Intracranial hemorrhage was lower with higher-dose NOACs than with warfarin irrespective of VHD (RR: 0.47; 95% CI: 0.24 to 0.93, and 0.49; 95% CI: 0.41 to 059, respectively; interaction p = 0.91). No protective effect of higher-dose NOACs in preventing all-cause death seemed to be present in patients with VHD versus without VHD (RR:1.01; 95% CI: 0.90 to 1.14 vs. RR: 0.88; 95% CI: 0.82 to 0.94, respectively; interaction p = 0.03).

Conclusions

High-dose NOACs provide overall efficacy and safety similar in AF patients with or without VHD.

Key Words

atrial fibrillation
bleeding
death
major bleeding
stroke
systemic embolism
valvular heart disease

Abbreviations and Acronyms

AF
atrial fibrillation
CHADS2
congestive heart failure, hypertension, age >75 years, diabetes mellitus, stroke
CI
confidence interval
ICH
intracranial hemorrhage
NOAC
non–vitamin K antagonist oral anticoagulant
RCT
randomized clinical trial
RR
risk ratio/relative risk
SSEE
stroke/systemic embolic events
SEM
standard errors of the mean
VHD
valvular heart disease
VKA
vitamin K antagonist

Cited by (0)

Dr. Renda has received consultant and speaker fees from Boehringer Ingelheim, Daiichi-Sankyo, and Bayer. Dr. Giugliano has received research grants from Daiichi-Sankyo and Merck; honoraria from Daiichi-Sankyo and the American College of Cardiology; and consulting fees from Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Merck, Portola, and Pfizer. Dr. De Caterina has received research grant support from Boehringer Ingelheim, Bayer, Bristol-Myers Squibb/Pfizer, and Roche; and honoraria from Boehringer Ingelheim, Bayer, Bristol-Myers Squibb/Pfizer, Daiichi-Sankyo, AstraZeneca, Merck, Lilly, and Novartis. Dr. Ricci has reported that he has no relationships relevant to the contents of this paper to disclose.

Listen to this manuscript's audio summary by JACC Editor-in-Chief Dr. Valentin Fuster.

© 2017 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.