ALONE-AF: Safe to stop anticoagulant therapy after AF ablation for recurrence-free patients

For individuals without documented recurrence for at least a year following catheter ablation for atrial fibrillation (AF), discontinuing oral anticoagulant therapy results in more favourable outcomes than when continued, according to the ALONE-AF trial.

The primary outcome of the first occurrence of a composite of stroke, systemic embolism, and major bleeding at 2 years occurred in only one patient who discontinued anticoagulation therapy as opposed to eight who remained on therapy (0.3 percent vs 2.2 percent; absolute difference, –1.9 percentage points, 95 percent confidence interval [CI], −3.5 to −0.3; p=0.02). [JAMA 2025;doi:10.1001/jama.2025.14679]

The difference was primarily driven by a lower incidence of major bleeding events, noted senior investigator Dr Boyoung Joung from Yonsei University College of Medicine in Seoul, South Korea, who reported the findings at the ESC annual meeting.

None of the patients who discontinued oral anticoagulant therapy experienced major bleeding, while five of those who remained on therapy did (0 vs 1.4 percent; absolute difference, –1.4 percentage points, 95 percent CI, −2.6 to −0.2; p=0.03).

Meanwhile, the incidence of ischaemic stroke or systemic embolism was low and did not differ between the two discontinuation and continuation strategy groups (0.3 percent vs 0.8 percent; absolute difference, −0.5 percentage points, 95 percent CI, −1.6 to 0.6; p=0.34).

“Current guidelines advocate for continued oral anticoagulant therapy after successful ablation in patients deemed to have a significant risk of thromboembolism. However, these recommendations are solely based on observational studies,” Joung said. [Circulation 2024;149:e1-e156; Eur Heart J 2024;45:3314-3414; EP Europace 2024;26:euae043]

As such, “many patients who have had a successful ablation and have stroke risk factors remain on oral anticoagulation for the rest of their lives, although there is no evidence from randomized trials to indicate that this is necessary. Our findings indicate that lifelong oral anticoagulation might not be necessary in all patients who have had successful AF ablation at least 1 year previously,” he continued.

ALONE-AF

The trial was conducted in South Korea and involved 840 adult patients (mean age 64 years, 24.9 percent female, 67.6 percent had paroxysmal AF) who had at least one non–sex-related stroke risk factor (determined using the CHA2DS2-VASc score) and no documented recurrence of atrial arrhythmia for at least 1 year after successfully completing catheter ablation for AF. The mean duration between catheter alation for AF and enrolment was 3.6 years.

These patients were randomly assigned to discontinue oral anticoagulant therapy (n=417) or continue therapy with apixaban or rivaroxaban (n=423). All patients underwent routine ECG monitoring at each follow-up visit and 24- to 72-h Holter monitoring at least every 6 months.

At baseline, the mean CHA2DS2-VASc score was 2.1, with 10.7 percent of patients having a score of at least 4. The mean HAS-BLED score was 1.8. Most patients had undergone radiofrequency ablation (87.4 percent in the discontinuation group and 85.2 percent in the continuation group), and the few remaining patients had undergone cryoballoon ablation. Pulmonary vein isolation was performed in all cases.

Consistent results for the primary outcome were obtained in the per-protocol population and across all subgroups. “Notably, even among high-risk patients (CHA2DS2-VASc score ≥4), discontinuing anticoagulation was not associated with an increased stroke risk or an increased risk for the primary composite outcome,” according to Joung.

Unanswered questions

Study discussant Dr Madelene Carina Blomstrom-Lundqvist from Orebro University Hospital in Orebro, Sweden, highlighted several limitations in ALONE-AF that question how widely its findings can be applied.

First were patient selection issues. Blomstrom-Lundqvist pointed out that including a mix of patients with paroxysmal AF and persistent AF may be problematic, given that persistent AF carries a higher risk of AF recurrence and stroke. Furthermore, because there was no assessment of AF burden prior to ablation, it was unclear whether the patients were at high risk or at low risk, she said.

Second was the trial’s method for monitoring AF recurrence, which was not rigorous enough. The discussant noted that using a Holter monitor for up to 3 days may not very effective at detecting AF, given a sensitivity of less than 25 percent.

Finally, the finding that more strokes occurred in the group of patients that remained on oral anticoagulant therapy was unexpected, raising the question of whether this was influenced by a difference in comorbidity or AF burden, according to Blomstrom-Lundqvist.

Reasonable approach

“The current study provides some support that cessation of oral anticoagulant therapy, if desired, is reasonable and may even offer benefit, particularly in patients at higher bleeding risk,” said Drs Edward Gerstenfeld and Xiang Wen Lee both from the University of California, San Francisco, California, US, in a linked editorial. [JAMA 2025;doi:10.1001/jama.2025.14669]

“For patients at high stroke risk (CHA2DS2-VASc score >3 or prior stroke), we recommend continued anticoagulation until more data becomes available,” Gerstenfeld and Lee added.

An alternative approach to minimizing stroke risk for high-risk patients who are unable to tolerate anticoagulation is left atrial appendage occlusion (LAAO), the duo noted. “In our opinion, LAAO remains a viable option for [this group of patients], recognizing that there are some serious procedural risks related to the implant (2.8 percent) as well as risk of device leak or thrombus (approximately 2 percent) that may require resumption of anticoagulation.” [N Engl J Med 2025;392:1277-1287; Circulation 2021;143:1754-1762]