Original Investigation
Left Atrial Appendage Closure Versus Direct Oral Anticoagulants in High-Risk Patients With Atrial Fibrillation

https://doi.org/10.1016/j.jacc.2020.04.067Get rights and content
Under an Elsevier user license
open archive

Abstract

Background

Percutaneous left atrial appendage closure (LAAC) is noninferior to vitamin K antagonists (VKAs) for preventing atrial fibrillation (AF)–related stroke. However, direct oral anticoagulants (DOACs) have an improved safety profile over VKAs, and their effect on cardiovascular and neurological outcomes relative to LAAC is unknown.

Objectives

This study sought to compare DOACs with LAAC in high-risk patients with AF.

Methods

Left Atrial Appendage Closure vs. Novel Anticoagulation Agents in Atrial Fibrillation (PRAGUE-17) was a multicenter, randomized, noninferiority trial comparing LAAC with DOACs. Patients were eligible to be enrolled if they had nonvalvular AF; were indicated for oral anticoagulation (OAC); and had a history of bleeding requiring intervention or hospitalization, a history of a cardioembolic event while taking an OAC, and/or a CHA2DS2-VASc of ≥3 and HAS-BLED of >2. Patients were randomized to receive LAAC or DOAC. The primary composite outcome was stroke, transient ischemic attack, systemic embolism, cardiovascular death, major or nonmajor clinically relevant bleeding, or procedure-/device-related complications. The primary analysis was by modified intention to treat.

Results

A high-risk patient cohort (CHA2DS2-VASc: 4.7 ± 1.5) was randomized to receive LAAC (n = 201) or DOAC (n = 201). LAAC was successful in 181 of 201 (90.0%) patients. In the DOAC group, apixaban was most frequently used (192 of 201; 95.5%). At a median 19.9 months of follow-up, the annual rates of the primary outcome were 10.99% with LAAC and 13.42% with DOAC (subdistribution hazard ratio [sHR]: 0.84; 95% confidence interval [CI]: 0.53 to 1.31; p = 0.44; p = 0.004 for noninferiority). There were no differences between groups for the components of the composite endpoint: all-stroke/TIA (sHR: 1.00; 95% CI: 0.40 to 2.51), clinically significant bleeding (sHR: 0.81; 95% CI: 0.44 to 1.52), and cardiovascular death (sHR: 0.75; 95% CI: 0.34 to 1.62). Major LAAC-related complications occurred in 9 (4.5%) patients.

Conclusions

Among patients at high risk for stroke and increased risk of bleeding, LAAC was noninferior to DOAC in preventing major AF-related cardiovascular, neurological, and bleeding events. (Left Atrial Appendage Closure vs. Novel Anticoagulation Agents in Atrial Fibrillation [PRAGUE-17]; NCT02426944)

Key Words

atrial fibrillation
cardioembolic event
direct oral anticoagulant
left atrial appendage
stroke

Abbreviations and Acronyms

AF
atrial fibrillation
CEC
clinical endpoint committee
CI
confidence interval
DAPT
dual antiplatelet treatment
DOAC
direct oral anticoagulant
DSMB
Data Safety and Monitoring Board
HR
hazard ratio
IQR
interquartile range
LAA
left atrial appendage
LAAC
left atrial appendage closure
mITT
modified intention-to-treat
NMCRB
nonmajor clinically relevant bleeding
OAC
oral anticoagulant
sHR
subdistribution hazard ratio
TEE
transesophageal echocardiography
TIA
transient ischemic attack
VKA
vitamin K antagonists

Cited by (0)

This work was supported by a research grant from the Ministry of Health, Czech Republic (AZV 15-29565A). Dr. Osmancik has received occasional speaking honoraria from Bayer and Abbott. Dr. Taborsky has served on the Advisory Boards for Bayer and Pfizer. Dr. Kala has served on the Speakers Bureau and Advisory Board for Bayer; and has served on the Advisory Board and as a consultant for Boston Scientific. Dr. Poloczek has received speaking honoraria from Abbott. Dr. Haman has received speaking honoraria from Pfizer. Dr. Zemanek has received speaking honoraria from Abbott and Bayer. Dr. Widimsky has received honoraria from Bayer, Pfizer, and Boehringer Ingelheim. Dr. Reddy has received consulting income and grant support from Abbott Inc. and Boston Scientific Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Jacqueline Saw, MD, served as Guest Associate Editor for this paper. Deepak L. Bhatt, MD, MPH, served as Guest Editor-in-Chief for this paper.

The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC author instructions page.

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

Drs. Widimsky and Reddy are co-senior authors.