The global CHAMPION-AF clinical trial has reported significant findings regarding the WATCHMAN FLX™ Left Atrial Appendage Closure (LAAC) device. The device achieved non-inferiority compared to non-vitamin K antagonist oral anticoagulants (NOACs) for its primary efficacy endpoint in reducing stroke, cardiovascular death, or systemic embolism in patients with non-valvular atrial fibrillation (NVAF). Moreover, the study demonstrated the device's superiority in reducing non-procedural bleeding. These pivotal findings were presented at ACC.26 and simultaneously published in The New England Journal of Medicine.
Understanding Atrial Fibrillation and Stroke Risk
Atrial fibrillation (AF) is a prevalent heart rhythm disorder, affecting approximately 59 million people globally, and is strongly associated with an increased risk of stroke. For patients with non-valvular AF (NVAF), it is understood that more than 90% of heart-related blood clots form in the left atrial appendage (LAA).
The WATCHMAN technology provides a permanent solution by closing the LAA through a single procedure. This offers a compelling alternative to long-term oral anticoagulation therapies, which many patients struggle to adhere to consistently.
CHAMPION-AF Trial: Design and Demographics
The CHAMPION-AF trial was a prospective, multinational, randomized controlled study designed to assess the WATCHMAN FLX device against standard NOAC therapy. It enrolled 3,000 patients with NVAF who were deemed suitable for long-term oral anticoagulation.
Participants had a mean age of 71.7 to 72 years, with approximately 32% women. The patient cohort was 85% White. Patients exhibited a moderately elevated stroke risk (average CHA2DS2-VASc score of 3.5) and a low bleeding risk (mean HAS-BLED score of 1.3).
Patients were randomized into two distinct groups: 1,501 received a NOAC, and 1,499 underwent LAA closure using the WATCHMAN FLX device. The trial was conducted across 141 sites in the U.S., Canada, Europe, Japan, and Australia, achieving an impressive 99% procedural success rate for device implantation. Primary results were reported after 36 months of follow-up, with continued patient observation planned for a total of five years.
Key Efficacy Outcomes: Non-Inferiority Demonstrated
The trial's primary efficacy endpoint was a composite rate of stroke, cardiovascular or unexplained death, or systemic embolism.
- After three years, this endpoint occurred in 5.7% of the LAA closure group and 4.8% of the NOAC group.
- The WATCHMAN FLX device met the criteria for statistical non-inferiority compared to NOACs (P<0.001).
When examining individual components of the primary endpoint:
- Ischemic stroke and systemic embolism were numerically higher in the LAA closure arm (3.2%) compared to the NOAC arm (2.2%).
- Cardiovascular death occurred at 2.7% in both groups.
- No significant differences were observed in the rates of hemorrhagic stroke or systemic embolism when considered individually.
Significant Safety Results: Reduced Bleeding Risk
Non-Procedural Bleeding: A Primary Safety Endpoint
The primary safety endpoint focused on non-procedural major and clinically relevant non-major bleeding.
- The LAA closure group experienced a rate of 10.9% compared to 19.0% in the NOAC group.
- The WATCHMAN FLX device demonstrated statistical superiority to NOACs for this endpoint (P<0.001), representing a 45% relative reduction in non-procedural bleeding risk.
Overall Bleeding and Procedural Events
- Overall Bleeding (including procedural bleeding): A secondary analysis that included both procedural and non-procedural major and clinically relevant non-major bleeding reported rates of 12.8% for the LAA closure group and 19.0% for the NOAC group, indicating a 34% relative reduction in overall bleeding risk for the device group (P<0.001).
- ISTH Major Bleeding: When specifically combining procedure-related and non-procedure-related ISTH major bleeding, the rates were 5.9% for the LAA closure arm and 6.4% for the NOAC arm, meeting non-inferiority criteria (P<0.001).
- Procedure-Related Adverse Events: Pericardial effusions occurred in 0.7% of patients, device-related thrombus was detected in 4.8% of imaged patients, and the rate of procedure-related serious adverse events was 2.3%.
Expert Perspectives and Clinical Implications
Investigators and medical experts have provided varied perspectives on the trial's implications:
- Potential Alternative: Study co-chair Dr. Martin Leon and co-principal investigator Dr. Saibal Kar suggested that the data indicate LAA closure could be considered a potential alternative to NOACs for suitable AF patients, warranting discussion in shared decision-making processes. They noted that patients might accept a potentially small increase in ischemic stroke risk to discontinue daily medications.
- Support for Guidelines: Brad Sutton, M.D., chief medical officer at Atrial Fibrillation Solutions, Boston Scientific, stated that these data could support updated clinical guidelines globally and inform submissions to expand the indication and coverage for the WATCHMAN platform. He highlighted that 40% of AF patients prescribed blood thinners for stroke risk reduction do not take their medications consistently, increasing their stroke risk.
However, some physicians raised reservations and considerations:
- Concerns included the trial's industry funding, lower-than-expected event rates that might have facilitated non-inferiority achievement, and the numerically higher number of primary endpoint events and ischemic strokes in the LAAO arm.
- Concerns were also noted regarding the primary safety endpoint's focus solely on non-procedure-related bleeding, as well as potential long-term impacts of LAAO on hemodynamic/endocrine function, dementia risk, and effects of device leaks.
In an editorial comment, Gregory M. Marcus, MD, FACC, acknowledged the trial's value in offering LAA closure as an alternative in specific cases, particularly when considering the harms of long-term anticoagulation and patient preferences. However, he also stated that the current data are insufficient to broadly conclude that LAA closure is as effective as standard NOAC therapy for most AFib patients.
Current evidence generally suggests LAAO may be an option for patients with true contraindications to long-term DOAC therapy.
Device Background and Future Research
The WATCHMAN implant is recognized as the most implanted and studied LAAC device on the market, having been used in over 600,000 patients. The device was introduced in Europe in 2009 and approved by the U.S. Food and Drug Administration (FDA) in 2015. Patient follow-up for the CHAMPION-AF trial will continue through five years to further assess the long-term non-inferiority of LAA closure for ischemic stroke and systemic embolism.