Device-based left atrial appendage (LAA) closure was comparable to non-vitamin K antagonist oral anticoagulant (NOAC) therapy in reducing the combined rate of death from cardiovascular causes, stroke, or systemic embolism at three years in patients with atrial fibrillation (AFib) who were candidates for anticoagulation, based on findings from the CHAMPION-AF trial presented at ACC.26 and simultaneously published in NEJM. In addition, LAA closure was superior to long-term NOAC therapy for pre-specified non–procedure-related bleeding over the same time period.

CHAMPION-AF is the first prospective, multinational, randomized trial to test whether LAA closure is noninferior to NOACs in patients who are able to take long-term blood thinners irrespective of whether they have undergone prior AFib ablation. The study included 3,000 patients (average age 72 years, 32% women, 85% White) with non-valvular AFib who had a moderately elevated risk of stroke (average CHA2DS2-VASc score of 3.5) and low bleeding risk (mean HAS-BLED score of 1.3) at 141 sites across the U.S., Australia, Belgium, Canada, Denmark, France, Germany, Israel, Italy, Japan, Netherlands, Poland, Saudi Arabia, Spain, Switzerland and the UK.

A total of 1,501 patients were randomized to receive a NOAC at the discretion of the treating physician and 1,499 were randomized to undergo LAA closure with the WATCHMAN FLX device. After three years of follow-up, 5.7% of patients in the LAA closure group and 4.8% of those in the medical therapy group experienced the trial’s primary efficacy endpoint – a composite rate of ischemic stroke, hemorrhagic stroke, cardiovascular death and systemic embolism – which met noninferiority.

“Our data suggest that the LAA closure device used in this trial is a potential and reasonable alternative to medication, even among patients who are suitable for long-term blood thinners, and may be discussed as part of a shared decision-making process,” said Saibal Kar, MD, FACC, co-principal investigator of the study.

Broken down by individual components, researchers found no difference in deaths, systemic embolism or hemorrhagic strokes, but observed slightly more ischemic strokes among those undergoing the LAA closure procedure (3.2% vs. 2%). Results for the primary safety endpoint – the combined occurrence of major and non-major, but clinically relevant, non-procedural bleeding at three years – showed that those in the medical therapy group had almost twice the rate of bleeding events. Bleeding occurred in 10.9% of those in the LAA closure group and 19% of those in the medical therapy group.

“This is an important finding because we studied people who we thought were good candidates for blood thinners – they are not contraindicated for long-term anticoagulation and they have low bleeding risk— and in spite of that, they had increased bleeding over time,” said Kar.

The team also conducted a secondary analysis that looked at major and clinically relevant non-major procedural and non-procedural bleeding and found that at three years, the LAA closure group had fewer events compared to the medical therapy group (12.8% vs. 19%, respectively).

Kar and team will follow patients for five years to determine whether LAA closure is noninferior to NOACs for ischemic stroke and systemic embolism over the longer term.

In a related editorial comment, Gregory M. Marcus, MD, FACC, highlights the valuable contributions of CHAMPION-AF in demonstrating LAA closure as an alternative to NOACs in some patients. He notes the potential long-term harms of anticoagulation, patient preferences, and the importance of shared decision-making free from financial bias as factors that might support LAA closure over NOACs on a case-by-case basis. However, the data are insufficient to conclude that this approach is broadly as effective as standard NOAC therapy for most patients with AFib, he writes.

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Anticoagulation Management and Atrial Fibrillation, Atrial Fibrillation/Supraventricular Arrhythmias

Keywords: ACC Annual Scientific Session, ACC26, New Orleans, Anticoagulants, Atrial Appendage, Atrial Fibrillation, Hemorrhagic Stroke, Ischemic Stroke, Embolism