Catheter-based closure of the left atrial appendage is considered an established alternative to anticoagulation therapy for preventing life-threatening strokes in patients with atrial fibrillation – particularly in those at increased risk of bleeding. However, a multicentre study now published in the New England Journal of Medicine, led by the DHZC in collaboration with AFNET e.V. and funded by the German Centre for Cardiovascular Research (DZHK), shows that in high-risk patients, catheter-based atrial appendage closure offered no advantage over anticoagulation therapy alone. For the first time, the results provide a robust basis for clinical decision-making in this particularly vulnerable patient group.
Atrial fibrillation is a heart rhythm disorder in which the atria beat irregularly and often very rapidly. It is the most common heart rhythm disorder – in Germany alone, an estimated 1.5 to 2 million people are affected.
The condition can cause symptoms such as palpitations, exhaustion or shortness of breath. However, another complication is more dangerous: the irregular movement of the atria can lead to the formation of blood clots, which enter the bloodstream and trigger a stroke – the most serious consequence of atrial fibrillation.
Particularly in cases of persistent atrial fibrillation that cannot be effectively treated or eliminated in the long term, it is crucial to prevent this clot Formation.
A well-established standard – but with risks
The standard approach to stroke prevention involves the use of specific medicines, known as anticoagulants, to inhibit blood clotting. For many patients, this treatment is safe and well tolerated, and significantly reduces the risk of stroke.
However, there are people for whom the risk of bleeding is greatly increased under this treatment – for example, due to previous bleeding, impaired kidney function or other serious comorbidities. For them, long-term blood thinning poses a particular challenge.
An alternative for patients at high risk of bleeding
An alternative procedure was developed for this group of patients around two decades ago: catheter-based closure of the left atrial appendage. This is a pouch-like protrusion in the left atrium where most blood clots form.
An implant – known as an occluder – is inserted via a catheter to permanently seal this pouch. This prevents blood clots from the atrium from entering the bloodstream. Until the occluder has healed in place, patients must take medication for a limited period to prevent blood clots from forming on the occluder itself. After that, further blood-thinning treatment is generally no longer necessary. The procedure has become established in recent years and is used in particular for patients with atrial fibrillation and an increased risk of bleeding.
A direct comparison of atrial appendage closure and anticoagulation
Until now, no large-scale, randomised study conducted in real-world settings had investigated whether this interventional procedure is at least as effective as modern, individually tailored drug therapy in patients with a high risk of both stroke and bleeding.
A research consortium led by Prof. Dr Ulf Landmesser (Deputy Medical Director of the DHZC) investigated this question in the CLOSURE-AF-DZHK16 study. A total of 912 patients with atrial fibrillation were enrolled at 42 specialist centres. All had both a significantly increased risk of stroke and an increased risk of bleeding – meaning this was a particularly high-risk patient group.
Participants were randomly assigned to either catheter-based closure of the left atrial appendage or individually tailored medical therapy. In the medical therapy group, modern oral anticoagulants were predominantly used (in >80% of patients), provided they were medically appropriate.
The study investigated the frequency of serious events occurring during the course of the study – including strokes, major bleeding or cardiovascular deaths. Patients were followed up for a median period of three years.
Key findings
During the observation period, atrial appendage closure showed no advantage over drug therapy. The number of serious events – including strokes, severe bleeding or cardiovascular deaths – was higher in the intervention group than in the control group. The intended equivalence could therefore not be statistically demonstrated.
The study examined a group of patients with a very high risk of both stroke and bleeding – in other words, people for whom every therapeutic decision must be weighed up with particular care. For this high-risk group, no general benefit of the interventional procedure could be demonstrated.
Interpretation and further research needs
“Our findings show that we need to take a particularly nuanced approach when making decisions for patients at very high risk of stroke and bleeding,” says Prof. Ulf Landmesser, MD, Director of the DHZC Department of Cardiology, Angiology and Intensive Care Medicine at the Benjamin Franklin Campus and Principal Investigator of the study:
“Atrial appendage closure remains a relevant procedure that can reduce the risk of stroke. However, the crucial question is for which patient groups it actually provides additional benefit. This is precisely where further research is needed.”
Landmesser emphasises that the data will help to define indications more precisely: “In future, we need even more precise risk stratification. The aim must be to individualise treatment more closely – whilst taking both stroke and bleeding risks into account equally.”
“Particularly in the case of older patients with multiple conditions, we need a solid basis for our treatment decisions,” says Prof. Dr Carsten Skurk, co-investigator of the study. “The CLOSURE-AF-DZHK16 study provides, for the first time, robust data from a large randomised trial for these patients. Further studies must now clarify which patients benefit most from atrial appendage closure – and whether combining this with anticoagulant therapy could offer advantages.”
Implications for clinical practice and guidelines
Given the high prevalence of atrial fibrillation and an ageing population, the findings have direct relevance for clinical practice. They support a tailored, individualised approach to treatment decisions and will inform the further development of recommendations and guidelines.
CLOSURE-AF-DZHK16 was made possible by public funding from the German Centre for Cardiovascular Research (DZHK) and was conducted in collaboration with The Atrial Fibrillation Network (Kompetenznetz Vorhofflimmern e.V.). The publication in the New England Journal of Medicine underscores the international significance of the findings.
Source: Pressemitteilung DHZC
Original publication:
Landmesser U, Skurk C, Kirchhof P, et al. Left Atrial Appendage Closure or Medical Therapy in Atrial Fibrillation. N Engl J Med. Published online March 18, 2026. doi:10.1056/NEJMoa2513310
