Left Atrial Appendage CLOSURE in Patients with Atrial Fibrillation at High Risk of Stroke and Bleeding Compared to Medical Therapy - CLOSURE-AF

Nov 08, 2025

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Author/Summarized by Author:
Bridget G Lee, DO
Summary Reviewer:
Fred M. Kusumoto, MD, FACC; Michael Gurin, MD
Original Posted Date:
11/08/2025
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Contribution To Literature:

The CLOSURE-AF trial found that physician-directed standard medical therapy, which included anticoagulation medications when applicable, was better than left atrial appendage closure (LAAC) in patients with atrial fibrillation (AFib) and at high risk of stroke and major bleeding.

Study Design:

Design: Prospective, multicenter, randomized, open-label trial with blinded endpoint adjudication (PROBE design)

  • Randomization: 1:1
  • Sites: 46 centers in Germany
  • Total randomized patients: 912
  • Median follow-up: 3 years

Patient Characteristics:

  • Mean age: 79.5 years (LAAC) vs. 78.4 years (medical therapy)
  • Female: 38.6%

Inclusion Criteria:

  • Nonvalvular AFib
  • CHA2DS2-VASc score ≥2
  • High bleeding risk, defined by at least one of the following:
    • HAS-BLED score ≥3 
    • Prior major bleeding event (BARC ≥3)
    • Chronic kidney disease with eGFR 15–29 mL/min/1.73 m2

Exclusion Criteria:

  • End-stage renal disease (eGFR <15 mL/min/1.73 m2 or dialysis)
  • Decompensated or unstable heart failure
  • Severe liver failure
  • Pregnancy or breastfeeding
  • Active infection or endocarditis
  • Life expectancy <1 year
  • Another indication for chronic anticoagulation

Interventional Model: Patients were randomized (1:1) with blind endpoint adjudication to the following study arms.

  • LAAC Group: Patients received CE-marked, percutaneous transcatheter LAAC devices, followed by individualized post-procedural antithrombotic therapy, typically dual antiplatelet therapy for up to 3 months.
  • Medical Therapy Group: Patients received "physician directed best" medical therapy, including non-vitamin K oral anticoagulants (dabigatran, rivaroxaban, apixaban, edoxaban) when eligible, vitamin K antagonists (warfarin or phenprocoumon) when indicated, and no antithrombotic therapy when contraindicated.

Primary Endpoint: Time to first occurrence of a composite of:

  • Ischemic or hemorrhagic stroke
  • Systemic embolism
  • Cardiovascular or unexplained death
  • Major bleeding (BARC ≥3)

Secondary Endpoints: Individual components of the primary endpoint, including:

  • All-cause mortality
  • Major adverse cardiovascular and cerebrovascular events
  • Safety outcomes including procedural and device-related complications

Principal Findings:

Findings are listed in order of LAAC group versus (vs) medical therapy group with adjusted hazard ratios (HR).

Primary Composite Endpoint:

  • 16.83 vs. 13.27 events per 100 patient-years
  • HR 1.28 (95% CI 1.01–1.62)
  • Non-inferiority was not met; (P for noninferiority = 0.44).

Stroke (ischemic or hemorrhagic):

  • 2.65 vs. 2.66 events per 100 patient-years (HR 1.02)

Major bleeding:

  • 7.43 vs. 6.23 events per 100 patient-years (HR 1.21)

Cardiovascular or unexplained death:

  • 9.47 vs. 7.45 events per 100 patient-years (HR 1.25)

All-cause mortality:

  • 14.83 vs. 13.49 events per 100 patient-years (HR 1.12)

Safety Outcomes: Early (≤7 days) procedure-related events in the LAAC group, including:

  • Cardiac tamponade: 1.12%
  • Device embolization: 0.22%
  • Procedure-related TIA or embolic events: <0.5%
  • Major bleeding requiring transfusion: 4.04%
  • Procedure-related death: 0.44%

Interpretation:

In patients with AFib at high risk for both stroke and bleeding, percutaneous LAAC did not demonstrate noninferiority to physician-directed medical therapy for the composite outcome of stroke, systemic embolism, cardiovascular or unexplained death, or major bleeding over a median follow-up of 3 years. Event rates numerically favored medical therapy.

These findings emphasize the importance of careful patient selection and confirm that optimized medical therapy remains an effective treatment strategy in this high-risk population. Notably, newer-generation LAAC devices were not fully represented and may yield different outcomes.

References

Presented by Ulf Landmesser, MD, at the American Heart Association Scientific Sessions (AHA 2025), New Orleans, LA, Nov. 8, 2025.

Resources

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Anticoagulation Management and Atrial Fibrillation, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure

Keywords: AHA Annual Scientific Sessions, AHA25, Ischemic Attack, Transient, Hemorrhagic Stroke, Atrial Fibrillation, Atrial Appendage, Atrial Function, Left, Renal Insufficiency, Chronic, Renal Insufficiency, Kidney Failure, Chronic, Anticoagulants, Liver Failure, Vitamin K, Heart Failure, Hemorrhage, Endocarditis, Embolism