CHAMPION-AF
Left Atrial Appendage Closure or Anticoagulation for Atrial Fibrillation
Year of Publication: 2026
Authors: Doshi SK, Kar S, Nair DG, ..., Ellenbogen KA; for the CHAMPION-AF Investigators
Journal: The New England Journal of Medicine
Citation: Doshi SK, et al. N Engl J Med. 2026. DOI: 10.1056/NEJMoa2517213.
PDF: Clinical Question
Can left atrial appendage closure replace NOACs for stroke prevention in anticoagulation-eligible AF patients?
Bottom Line
In 3,000 patients with atrial fibrillation eligible for anticoagulation, left atrial appendage closure with the Watchman FLX device was noninferior to NOACs for preventing cardiovascular death, stroke, or systemic embolism at 3 years (5.7% vs 4.8%; HR 1.20; P<0.001 for noninferiority). The device arm had significantly less non-procedure-related bleeding (10.9% vs 19.0%; HR 0.55; P<0.001), establishing LAAC as a viable alternative even in anticoagulation-eligible patients.
Major Points
- First trial to demonstrate noninferiority of LAAC vs NOACs in anticoagulation-eligible AF patients — prior trials (PROTECT AF, PREVAIL) compared against warfarin only
- Primary efficacy (CV death, stroke, SE) at 3 years: 81 events (5.7%) device vs 65 events (4.8%) NOAC; difference 0.9 pp (95% CI −0.8 to 2.6); HR 1.20 (0.87–1.66); P<0.001 for noninferiority
- Primary safety (non-procedure-related bleeding, composite of ISTH major + clinically relevant nonmajor): 154 events (10.9%) device vs 260 events (19.0%) NOAC; HR 0.55 (0.45–0.67); P<0.001 for superiority
- Net clinical benefit (CV death, stroke, SE, or non-procedure-related bleeding): 15.1% device vs 21.8% NOAC; HR 0.66 (0.56–0.79); P<0.001 for noninferiority
- 1,386 of 1,499 assigned patients (92.5%) received the device; successful deployment in 1,386 (98.8%) of patients in whom implantation was attempted; effective closure (residual leak ≤3 mm) in 998/1,012 (98.6%) at 4 months
- Device-related thrombus in 63/1,320 patients (4.8%) assessed by imaging; 24 (1.8%) were clinically relevant, 2 had a stroke
- 206 patients (13.7%) in the anticoagulation group crossed over to the device group; 119 received a device before a primary endpoint event
- Annualized ischemic stroke/SE rate ~1.1%/year with device vs ~0.8%/year with NOAC — a 0.3% annual excess that needs 5-year assessment
Design
Study Type: Randomized, open-label, noninferiority trial
Randomization: 1
Blinding: Open-label with blinded endpoint adjudication
Enrollment Period: 2019-2023
Follow-up Duration: 3 years (5-year ongoing)
Centers: 141
Countries: 16
Sample Size: 3000
Power Calculation: 90% power to show noninferiority with 4.8 percentage point margin, assuming 12% event rate at 3 years, one-sided alpha 0.025, estimated attrition 12.5%
Analysis: Intention-to-treat
Registration: NCT04394546
Inclusion Criteria
- Age ≥18 years
- Non-valvular atrial fibrillation (paroxysmal, persistent, or permanent)
- CHA2DS2-VASc score ≥2 for men or ≥3 for women
- Suitable candidates for long-term oral anticoagulation
Exclusion Criteria
- Myocardial infarction, stroke, or TIA within 30 days before enrollment
- Major bleeding event (ISTH criteria) within prior 30 days
- Contraindication to oral anticoagulation
- Mechanical heart valve or moderate-to-severe mitral stenosis
- Left atrial appendage thrombus
- Prior left atrial appendage closure or surgical ligation
Baseline Characteristics
| Characteristic | Control | Active |
|---|---|---|
| N | 1501 | 1499 |
| Age (mean±SD) | 71.8±7.5 | 71.6±7.5 |
| Female | 31.5% | 32.4% |
| White | 85.0% | 85.1% |
| CHA2DS2-VASc (mean±SD) | 3.5±1.3 | 3.5±1.2 |
| HAS-BLED (mean±SD) | 1.3±0.8 | 1.3±0.8 |
| Previous ischemic stroke | 7.6% | 7.9% |
| Previous hemorrhagic stroke | 0.7% | 0.3% |
| Paroxysmal AF | 68.5% | 69.3% |
| Persistent AF | 25.4% | 23.9% |
| Permanent AF | 6.1% | 6.8% |
| Previous AF ablation | 46.9% | 48.7% |
Arms
| Field | Device: Watchman FLX | Control |
|---|---|---|
| Intervention | Percutaneous left atrial appendage closure with the Watchman FLX device (Boston Scientific). Post-implantation: NOAC plus aspirin, NOAC monotherapy, or dual antiplatelet therapy for 3 months, then aspirin or P2Y12 inhibitor monotherapy recommended. | Physician-choice non-vitamin K antagonist oral anticoagulant (apixaban, rivaroxaban, edoxaban, or dabigatran) at guideline-recommended doses for stroke prevention in AF. |
| Duration | 3 years follow-up | 3 years follow-up |
Outcomes
| Outcome | Type | Control | Intervention | HR / OR / RR | P-value |
|---|---|---|---|---|---|
| Composite of death from cardiovascular causes, stroke, or systemic embolism at 3 years | Primary | 4.8% (65 events) | 5.7% (81 events) | 1.2 | <0.001 for noninferiority |
| Non-procedure-related bleeding, composite of ISTH major + clinically relevant nonmajor (primary safety endpoint — superiority) | 95% CI: 0.45-0.67 | Secondary | 19.0% (260 events) | 10.9% (154 events) | 0.55 | <0.001 |
| Procedure-related and non-procedure-related ISTH major bleeding (secondary safety) | 95% CI: 0.68-1.24 | Secondary | 6.4% (87 events) | 5.9% (83 events) | 0.92 | <0.001 for noninferiority |
| Net clinical benefit (CV death, stroke, SE, or non-procedure-related bleeding) | 95% CI: 0.56-0.79 | Secondary | 21.8% (300 events) | 15.1% (215 events) | 0.66 | <0.001 for noninferiority |
| Death from cardiovascular causes | 95% CI: 0.64-1.59 | Secondary | 2.7% (36 events) | 2.7% (38 events) | 1.01 | |
| Stroke (ischemic or hemorrhagic) | 95% CI: 0.94-2.27 | Secondary | 2.5% (33 events) | 3.6% (50 events) | 1.46 | |
| Systemic embolism | Secondary | 0.1% (2 events) | 0% (0 events) | ||
| ISTH major bleeding (non-procedure-related) | 95% CI: 0.57-1.06 | Secondary | 6.4% (87 events) | 5.1% (71 events) | 0.78 | |
| Clinically relevant nonmajor bleeding (non-procedure-related) | 95% CI: 0.37-0.61 | Secondary | 14.2% (193 events) | 7.0% (99 events) | 0.48 | |
| All-cause death | Secondary | 4.9% (67 events) | 5.0% (71 events) | ||
| Ischemic stroke or systemic embolism | Secondary | 2.2% (29 events) | 3.2% (45 events) | ||
| Hemorrhagic stroke | Secondary | 0.4% (5 events) | 0.4% (5 events) | ||
| All bleeding events (3-year cumulative) | Secondary | 19.0% | 12.8% | ||
| Device-related thrombus | Adverse | N/A | 4.8% (63/1,320 assessed) | ||
| Clinically relevant device thrombus | Adverse | N/A | 1.8% (24 patients; 2 had stroke) | ||
| Pericardial effusion requiring intervention (≤30 days) | Adverse | N/A | 0.7% (10 patients) |
Subgroup Analysis
Results for the primary end points appeared to be consistent across most subgroups including age, sex, CHA2DS2-VASc score, type of AF, and prior stroke/TIA.
Criticisms
- Open-label design — despite blinded adjudication, knowledge of treatment assignment may influence patient behavior, medication adherence, and clinical decision-making
- Numerically higher stroke rate with device (3.6% vs 2.5%; HR 1.46) raises concern about a small efficacy trade-off; 5-year data needed to determine if this gap persists or widens
- Noninferiority margin of 4.8 percentage points on absolute scale is wide given low event rates — allows a potentially higher relative risk of events
- 13.7% crossover from anticoagulation to device group dilutes the between-group difference in an ITT analysis
- Only Watchman FLX tested — results cannot be extrapolated to other LAAC devices or techniques
- CHA2DS2-VASc ≥5 subgroup underrepresented (18.4%) — highest-risk patients who may have most to lose from any efficacy trade-off are less well studied
- Post-implantation antithrombotic protocol varied (NOAC+aspirin, NOAC alone, or DAPT for 3 months) — no standardized regimen
- Device-related thrombus in 4.8% of assessed patients, with CT imaging detecting more thrombus than TEE — clinical significance of CT-detected thrombus remains debated
Funding
Boston Scientific
Based on: CHAMPION-AF (The New England Journal of Medicine, 2026)
Authors: Doshi SK, Kar S, Nair DG, ..., Ellenbogen KA; for the CHAMPION-AF Investigators
Citation: Doshi SK, et al. N Engl J Med. 2026. DOI: 10.1056/NEJMoa2517213.
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