Expert Analysis · Arrhythmias & Clinical EP

LAAO vs. Medical Therapy in High-Risk AF: What CLOSURE-AF Means for Practice

Cardiology Blog Team | Physician Education Series | Updated June 2026

A new randomized trial is reshaping how cardiologists think about left atrial appendage occlusion in the sickest atrial fibrillation patients.

For years, catheter-based LAAO has been pitched as a stroke-prevention strategy for patients who cannot tolerate long-term anticoagulation.

The CLOSURE-AF trial tested that premise specifically in patients at high risk for both stroke and bleeding, and the results complicate the prevailing narrative.

What CLOSURE-AF Tested

CLOSURE-AF was a pragmatic, multicenter randomized trial conducted across 42 German centers.

The trial enrolled 888 patients with a mean age of 78 years and substantial comorbidity burden, reflected in a mean CHA2DS2-VASc score of 5.2 and a mean HAS-BLED score of 3.0.

Patients were randomized to catheter-based LAAO (446 patients) or physician-directed best medical therapy (442 patients), of whom 85% received a direct oral anticoagulant (DOAC).

The primary composite endpoint combined stroke, systemic embolism, major bleeding, and cardiovascular or unexplained death over a median follow-up of three years.

The Headline Result

LAAO failed to demonstrate noninferiority against medical therapy for the primary composite endpoint.

Event rates were numerically higher in the device arm, at 16.8 versus 13.3 events per 100 patient-years.

Stroke rates were nearly identical between groups, at 2.6 versus 2.7 events per 100 patient-years.

Critically, major bleeding was not reduced with LAAO despite the avoidance of long-term anticoagulation, undercutting a core rationale for offering the procedure to bleeding-prone patients.

Serious adverse events occurred more often in the device arm, 82.5% versus 77.4%, and periprocedural complications affected 5.7% of implanted patients.

Endpoint	LAAO (per 100 pt-yrs)	Medical Therapy (per 100 pt-yrs)
Primary composite endpoint	16.8	13.3
Stroke	2.6	2.7
Serious adverse events (overall, %)	82.5%	77.4%
Periprocedural complications	5.7%	—

Figure 1. CLOSURE-AF primary composite endpoint and stroke rates, LAAO vs. medical therapy.

How This Fits With Prior Evidence

Earlier randomized trials had already established noninferiority of LAAO against DOAC therapy in broader AF populations.

CLOSURE-AF is distinct because it specifically enrolled patients at high risk for both stroke and bleeding, a population not directly represented in those earlier studies.

That distinction matters because this is precisely the population in which clinicians most often consider LAAO as an anticoagulation-sparing option.

Two other trials help frame the broader landscape: the CHAMPION-AF trial found that device-based closure with the Watchman FLX system was noninferior to NOAC therapy and reduced non-procedure-related bleeding at three years, while the ongoing CATALYST trial is evaluating the Amplatzer Amulet device against NOAC therapy.

Taken together, these trials suggest that patient selection, rather than the LAAO concept itself, may be the determining factor in whether device-based closure outperforms medical therapy.

Devices, Manufacturers, and Cost Context

The two leading commercial LAAO platforms are the Watchman FLX device, manufactured by Boston Scientific (NYSE: BSX), and the Amplatzer Amulet device, manufactured by Abbott Laboratories (NYSE: ABT).

For context, BSX shares trade in the mid-$40s and ABT shares trade in the mid-$90s, with both companies maintaining substantial structural-heart device franchises.

A typical Medicare beneficiary's out-of-pocket cost for the Watchman implant is estimated at no more than $3,318 under current Part A and Part B cost-sharing rules, a figure that excludes the facility and device acquisition costs borne by the health system.

Device	Generic/Class	Manufacturer (Ticker)	Typical Medicare Patient OOP Cost
Watchman FLX	Percutaneous LAA closure device	Boston Scientific (BSX)	≤$3,318
Amplatzer Amulet	Percutaneous LAA closure device	Abbott (ABT)	Comparable Medicare cost-sharing structure
DOAC therapy (class)	Direct oral anticoagulant	Multiple manufacturers	Variable by plan and formulary tier

Case Vignette

A 79-year-old with permanent AF, prior gastrointestinal bleed, and a CHA2DS2-VASc score of 6 is referred for LAAO after his primary team flags him as a poor anticoagulation candidate.

Before proceeding, the consulting cardiologist now has trial-level evidence that LAAO in patients with this combined high stroke-and-bleeding profile has not shown a net benefit over optimized medical therapy, including bleeding rates.

This prompts a more structured shared decision-making conversation, including a trial of dose-adjusted DOAC therapy with bleeding-mitigation strategies before defaulting to device closure.

Limitations Worth Knowing

CLOSURE-AF was not powered to detect differences in individual endpoint components, limiting conclusions about any single outcome such as bleeding alone.

The trial was conducted exclusively in Germany in a predominantly White cohort, which limits generalizability to more diverse populations.

The study also underwent two sample-size reductions based on interim analyses, a design feature that can affect statistical power.

Practice Implications

For patients at high combined risk of stroke and bleeding, CLOSURE-AF reinforces that DOAC therapy should remain the default strategy whenever tolerated.

LAAO still has a defined role for patients with a true contraindication to long-term anticoagulation, but this trial argues against expanding that role to dual high-risk patients simply because bleeding risk is elevated.

Procedural risk is not trivial in this older, sicker population, and the 5.7% periprocedural complication rate should factor directly into the consent conversation.

Ongoing trials including CHAMPION-AF and CATALYST will help define which specific subgroups, if any, derive a net benefit from device-based closure.

Bottom Line

In patients at high risk for both stroke and bleeding, catheter-based LAAO did not outperform optimized medical therapy in CLOSURE-AF, and bleeding rates were not reduced despite anticoagulation avoidance.

Careful patient selection, not blanket extension to all high-bleeding-risk patients, should guide referral for LAAO until further trial data clarify which subgroups benefit.

Figure 2. Comparative trial landscape for LAAO in atrial fibrillation, by population risk profile.

References

1. American College of Cardiology. CLOSURE-AF: LAA Closure Noninferior to Medical Therapy in High-Risk AFib Patients. Journal Scan, March 2026.
2. American College of Cardiology. CHAMPION-AF: Left Atrial Appendage Closure vs. Anticoagulation for AFib. ACC.26 Coverage, March 2026.
3. Boston Scientific. WATCHMAN LAAC Medicare Patient Cost Information for Physicians, 2026.

This article is intended for physician education and does not constitute personalized medical, legal, or financial advice; clinical decisions should be individualized and any investment-related content reflects general financial education only, not a recommendation to buy or sell any security.