CHAMPION-AF Trial Fails to Overturn Anticoagulation for Atrial Fibrillation

Cardiologist John Mandrola argues the data is too weak to replace the gold standard of oral anticoagulants for stroke prevention in atrial fibrillation patients.

Mar. 28, 2026 at 2:55pm

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The CHAMPION-AF trial compared the Watchman FLX percutaneous left atrial appendage closure (LAAC) device to direct-acting oral anticoagulants (DOACs) for stroke prevention in atrial fibrillation patients. While the trial was presented as 'positive', cardiologist John Mandrola argues the data is far too weak to overturn the strong evidence supporting anticoagulation as the standard of care. Mandrola outlines six key reasons why CHAMPION-AF should not change clinical practice, including a higher stroke rate in the LAAC arm, flawed noninferiority margins, safety endpoint issues, and an overall lack of a clear net clinical benefit.

Why it matters

Millions of atrial fibrillation patients worldwide rely on oral anticoagulants to prevent devastating strokes. Any new therapy aiming to replace this gold standard treatment must have unassailable evidence. Mandrola argues the CHAMPION-AF data falls far short of that bar, and accepting it could lead to one of the 'gravest errors' in modern medicine by exposing patients to higher stroke risk.

The details

The CHAMPION-AF trial randomly assigned 3,000 atrial fibrillation patients to either the Watchman FLX LAAC device or DOACs. The primary efficacy endpoint of stroke, systemic embolism, and cardiovascular death occurred in 5.7% of the Watchman arm vs. 4.8% of the DOAC arm. While the authors claimed noninferiority, Mandrola argues the noninferiority margin was far too generous and that a standard margin would not have been met. Additionally, the primary safety endpoint excluded procedural bleeding, assuring a positive but clinically meaningless result. Mandrola also notes the Watchman arm had a 46% higher rate of ischemic stroke compared to DOACs, and failed to show a reduction in major bleeding events.

  • CHAMPION-AF was presented as a late-breaking trial at the 2026 American College of Cardiology meeting.

The players

John M. Mandrola

A cardiac electrophysiologist practicing in Louisville, Kentucky, who writes and podcasts for Medscape, and espouses a conservative approach to medical practice.

Watchman FLX

A percutaneous left atrial appendage closure (LAAC) device.

Direct-acting oral anticoagulants (DOACs)

A class of medications used to prevent stroke in atrial fibrillation patients.

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What they’re saying

“If the mechanical strategy of LAAC could provide equivalent or better outcomes than anticoagulation, it would be a huge advance. Given the strength of evidence for anticoagulation in AF, the evidence must be unassailable.”

— John M. Mandrola, Cardiologist

“To change practice and upend one of the most evidence-based therapies in medicine, you need safety to be superior, especially when patients have to accept the possibility of a 66% higher rate of stroke, systemic embolism, or CV death.”

— John M. Mandrola, Cardiologist

What’s next

Mandrola predicts a narrative may emerge trying to position the Watchman device as an alternative to long-term oral anticoagulation for atrial fibrillation patients. He argues professional societies and clinicians should publicly reject this 'marketing ploy' given the weak evidence from CHAMPION-AF.

The takeaway

This case highlights the high bar that must be met to overturn one of medicine's most well-established and evidence-based treatments. Despite being presented as a 'positive' trial, the CHAMPION-AF data is far too weak to justify replacing oral anticoagulants with the Watchman LAAC device for stroke prevention in atrial fibrillation patients.