Discontinuing Anticoagulants for Atrial Fibrillation

(DESTINATION Trial)

Not yet recruiting at 11 trial locations

Overseen By Lingmin Wu, Phd

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: China National Center for Cardiovascular Diseases

Must be taking: Anticoagulants

Must not be taking: CYP3A inducers, CYP3A inhibitors

Disqualifiers: Valvular AF, Reversible AF, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine whether people with atrial fibrillation (AF) need to continue taking blood-thinning drugs (anticoagulants) after a successful catheter ablation procedure, which restores normal heart rhythm. Typically, patients continue these medications to prevent strokes, but they carry a risk of serious bleeding. The study will compare two groups: one that continues the medication and another that stops, to assess which group experiences fewer complications. Individuals who have had a successful ablation without AF recurrence after 3 to 12 months and have been diagnosed with AF may be suitable for this trial. The goal is to evaluate whether guidelines can be updated to enhance safety and treatment for AF patients. As an Early Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants a chance to contribute to groundbreaking insights.

Will I have to stop taking my current medications?

The trial focuses on whether patients can stop taking anticoagulants (blood thinners) after a successful ablation for atrial fibrillation. It does not specify if you need to stop other medications, so you should discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Past research has shown that catheter ablation for atrial fibrillation is generally safe, with complications being rare. One study found that only 0.4% of patients experienced temporary nerve injury. Most patients do not encounter serious problems after the procedure, and safety has improved over time.

Anticoagulant drugs like dabigatran, rivaroxaban, and apixaban are well-known for treating blood clots and have FDA approval for other uses. This suggests they are generally safe when used properly, though all blood thinners carry some risk of bleeding.

The current trial is in its early stages and primarily focuses on safety. As a result, there is limited information on how these treatments work in this specific setting. However, previous data indicate that both catheter ablation and anticoagulants have a good safety record. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores the possibility of safely discontinuing anticoagulant drugs, like dabigatran, rivaroxaban, and apixaban, for patients with atrial fibrillation who have undergone catheter ablation. Traditionally, patients with atrial fibrillation rely on continuous anticoagulant therapy to prevent stroke. This study seeks to find out if stopping these medications post-ablation could reduce the risk of bleeding and improve quality of life without increasing stroke risk. If successful, this could lead to a significant shift in managing atrial fibrillation, potentially offering a safer and more convenient approach for many patients.

What evidence suggests that discontinuing anticoagulation therapy after catheter ablation might be effective for atrial fibrillation?

Studies have shown that catheter ablation, a procedure that creates small scars in the heart to help it beat normally, can effectively treat atrial fibrillation (AF). Research indicates that about 85% of patients remain free of AF without extra medication for three years, though this number drops to 71% after five years. Another study found a 63.5% success rate at one year for those with persistent AF. In this trial, one group of participants will continue using blood-thinning drugs like dabigatran, rivaroxaban, and apixaban, which effectively lower the risk of blood clots and stroke. However, these drugs can also increase the risk of bleeding. Another group in this trial will discontinue anticoagulant therapy after successful ablation to evaluate their necessity post-ablation. Overall, both treatments have proven effective, but their roles after ablation remain under investigation. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for patients with atrial fibrillation who've had a successful catheter ablation and have been free of AF recurrence for 6-12 months. They must be willing to use smart wearable monitors and participate in the study for 24 months.

Inclusion Criteria

Signed informed consent

I have been diagnosed with a form of irregular heartbeat.

I had a successful ablation with no issues for 3 months.

Exclusion Criteria

Pregnancy/breast feeding

I have had a procedure to correct atrial fibrillation.

I have a serious heart valve condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomly assigned to either continue or discontinue anticoagulation therapy, monitored with smart wearable devices

24 months

Follow-up visits at 3, 6, 12, 18, and 24 months

Follow-up

Participants are monitored for thromboembolic and bleeding events, as well as AF recurrence

24 months

Data from wearable devices transmitted continuously

What Are the Treatments Tested in This Trial?

Interventions

• Anticoagulant drugs
• Catheter Ablation
• discontinue anticoagulation therapy

Trial Overview The DESTINATION Study is testing if stopping anticoagulant drugs after successful catheter ablation reduces bleeding without increasing stroke risk. Patients are randomly chosen to either continue or stop taking these blood thinners.

How Is the Trial Designed?

Group I: off-OAC Experimental Treatment 2 Interventions

In the off-OAC, involving the discontinuation of OAC therapy, patients had their OAC treatment terminated post-randomization, and no placebo medication was administered as a substitute.

Group II: on-OAC Active Control 2 Interventions

In the cohort assigned to the "on-OAC" arm, which entails the continuation of Oral Anticoagulant (OAC) therapy, patients were prescribed Non-Vitamin K Antagonist Oral Anticoagulants (NOACs), specifically dabigatran, rivaroxaban, or apixaban, for a duration of 24 months following randomization. The dosing regimen was as follows: (1) Standard dosage included rivaroxaban at 20mg daily, apixaban at 5mg twice daily, and dabigatran at 150mg twice daily. (2) Reduced dosage was administered in cases where patients were aged over 75 years, had a body weight less than 50kg, or exhibited creatinine clearance below 50ml/min.

Who Is Running the Clinical Trial?

China National Center for Cardiovascular Diseases

Lead Sponsor

Trials

196

Recruited

5,067,000+

Published Research Related to This Trial

The STOP Persistent AF trial showed that cryoballoon ablation is a safe and effective treatment for patients with drug-refractory persistent atrial fibrillation, achieving a 54.8% success rate in maintaining freedom from AF, AFL, or AT at 12 months.

With only one primary safety event reported (0.6% rate), the procedure demonstrated a favorable safety profile, alongside significant improvements in quality of life as measured by the AFEQT and SF-12 questionnaires.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cryoballoon ablation of pulmonary veins for persistent atrial fibrillation: Results from the multicenter STOP Persistent AF trial. Su, WW., Reddy, VY., Bhasin, K., et al.[2021]

In a study of 486 patients with persistent and long-standing persistent atrial fibrillation (AF) treated with cryoballoon ablation, the procedure demonstrated a high acute success rate of 97.6% for pulmonary vein isolation (PVI).

The procedure was found to be safe, with a low complication rate of 4.3%, and showed reasonable mid-term success rates for freedom from AF, with 63.9% of patients remaining event-free at 12 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulmonary vein isolation cryoablation for patients with persistent and long-standing persistent atrial fibrillation: Clinical outcomes from the real-world multicenter observational project. Tondo, C., Iacopino, S., Pieragnoli, P., et al.[2018]

In a study of 13,823 patients undergoing pulmonary vein isolation (PVI) for atrial fibrillation, the overall complication rate was low at 3.6%, but patients treated with conventional radiofrequency (C-RF) had higher rates of cardiac tamponades and vascular complications compared to other methods.

Female patients were found to be at a higher risk for complications, with nearly three times the odds of experiencing cardiac tamponade and double the odds of bleeding complications compared to male patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications in pulmonary vein isolation in the Netherlands Heart Registration differ with sex and ablation technique. Mol, D., Houterman, S., Balt, JC., et al.[2021]

Patients with atrial fibrillation (AF) who underwent pulmonary vein isolation plus additional atrial ablations (PVI+) had a significantly higher rate of maintaining normal sinus rhythm in the first year compared to those who only had PVI, with a relative risk of 1.10 based on 21 randomized controlled trials and 3 non-randomized trials.

The most notable improvement was seen with PVI+ left atrial linear ablations, which showed a relative risk of 1.16, indicating that this specific approach may enhance the effectiveness of AF treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of catheter ablation strategies for rhythm control in patients with atrial fibrillation: a meta-analysis. Assasi, N., Xie, F., Blackhouse, G., et al.[2021]

Pulmonary vein isolation (PVI) significantly increases the chances of remaining free from atrial fibrillation (AF) at 12 months, with 77% of patients achieving this compared to only 29% in those receiving medical therapy, based on a meta-analysis of 6 trials involving 693 patients.

While PVI does carry a risk of major complications (2.6%), this risk is comparable to other interventional procedures, and PVI also leads to fewer hospitalizations for cardiovascular issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulmonary vein isolation for the maintenance of sinus rhythm in patients with atrial fibrillation: a meta-analysis of randomized, controlled trials. Piccini, JP., Lopes, RD., Kong, MH., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2892619/

Five-Year Outcomes after Segmental Pulmonary Vein ... Overall five-year outcomes after PVI for PAF are consistent with previously reported shorter term follow-up (≤2 years); however, late recurrences (>2 years) ...

2. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2800186

Effect of Catheter Ablation Using Pulmonary Vein Isolation ... There was a significant reduction in recurrent arrhythmias with the hybrid surgical approach; however, serious adverse events were reported in ...

3. heartrhythmjournal.com heartrhythmjournal.com/article/S1547-5271(25)02379-3/fulltext

One-year outcomes of a conformable single-shot pulsed ... The secondary efficacy outcomes were (1) chronic efficacy, defined as freedom from >30 second AA recurrence excluding a 90-day blanking period, ...

4. ahajournals.org ahajournals.org/doi/10.1161/circep.109.923771

Long-Term Outcome After Successful Catheter Ablation of ... AF freedom off AAD was 85% at 3 years and 71% at 5 years, with an approximate 7% per year late recurrence rate after the first year. Patients ...

5. jacc.org jacc.org/doi/10.1016/j.jacc.2025.03.515

Pulsed Field Ablation for Persistent Atrial Fibrillation Primary effectiveness was 63.5% (57.3% lower confidence limit) at 1 year, with 8.5% patients having a single, isolated atrial fibrillation ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30593868/

Safety and Outcomes of Catheter Ablation for Atrial ... Overall, complete and complete/partial freedom was achieved at 1 year in 53.1% and 71.6%, respectively, with no significant differences between those with ...

7. heartrhythmjournal.com heartrhythmjournal.com/article/S1547-5271(25)00125-0/fulltext

Safety and efficacy of catheter ablation for atrial fibrillation ... Five patients met secondary safety outcomes. In the CB group, 2 patients (0.4%) sustained transient phrenic nerve injury but were discharged the ...

8. jacc.org jacc.org/doi/10.1016/j.jacc.2023.03.418

Procedure-Related Complications of Catheter Ablation for ... Procedure-related complications and mortality rates associated with catheter ablation of AF are low and have declined in the past decade.

9. academic.oup.com academic.oup.com/europace/article/23/6/851/6101617

Safety, effectiveness, and quality of life following pulmonary ... Pulmonary vein isolation (PVI) with radiofrequency (RF) catheter ablation is an effective treatment option for patients with paroxysmal atrial ...