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

J Am Coll Cardiol. 2020 Jun 30;75(25):3122-3135. doi: 10.1016/j.jacc.2020.04.067.

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).

Keywords: atrial fibrillation; cardioembolic event; direct oral anticoagulant; left atrial appendage; stroke.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Atrial Appendage / diagnostic imaging
  • Atrial Appendage / surgery*
  • Atrial Fibrillation / complications
  • Atrial Fibrillation / diagnosis
  • Atrial Fibrillation / drug therapy
  • Atrial Fibrillation / surgery*
  • Cardiac Surgical Procedures* / adverse effects
  • Cardiac Surgical Procedures* / instrumentation
  • Cardiac Surgical Procedures* / methods
  • Factor Xa Inhibitors* / administration & dosage
  • Factor Xa Inhibitors* / adverse effects
  • Female
  • Hemorrhage* / chemically induced
  • Hemorrhage* / prevention & control
  • Humans
  • Male
  • Outcome and Process Assessment, Health Care
  • Prosthesis Implantation* / adverse effects
  • Prosthesis Implantation* / instrumentation
  • Prosthesis Implantation* / methods
  • Stroke* / etiology
  • Stroke* / prevention & control

Substances

  • Factor Xa Inhibitors

Associated data

  • ClinicalTrials.gov/NCT02426944