Discontinuing Anticoagulants for Atrial Fibrillation

(DESTINATION Trial)

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

3160 Participants Needed

Trial Summary

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.

What data supports the effectiveness of discontinuing anticoagulants after catheter ablation for atrial fibrillation?

Pulmonary vein isolation (PVI), a key part of catheter ablation, is shown to be effective in treating atrial fibrillation, as it helps manage symptoms and is included in treatment guidelines for cases where drugs don't work. However, detecting atrial fibrillation recurrence after PVI is crucial if stopping anticoagulants is considered. ^{1 2 3 4 5}

Is it safe to discontinue anticoagulants for atrial fibrillation using catheter ablation?

Catheter ablation, specifically pulmonary vein isolation (PVI), is generally safe for treating atrial fibrillation, but severe complications can occur in 1-3% of patients. It's important to discuss potential risks with your doctor. ^{1 3 6 7 8}

How is catheter ablation treatment for atrial fibrillation different from other treatments?

Catheter ablation, specifically pulmonary vein isolation (PVI), is unique because it targets the electrical pathways in the heart to restore normal rhythm, unlike medications that manage symptoms or prevent blood clots. This procedure is often used when medications are ineffective, and it can potentially allow patients to discontinue anticoagulant drugs if successful. ^{1 3 9 10 11}

What is the purpose of this trial?

The DESTINATION Study investigates whether anticoagulation therapy is necessary after successful catheter ablation (CA) for atrial fibrillation (AF). Current guidelines recommend continued anticoagulation based on stroke risk scores, even post-ablation, potentially exposing patients to unnecessary bleeding risks. This international, multicenter, randomized controlled trial aims to compare thromboembolic and bleeding event risks between patients who continue and discontinue anticoagulation after ablation. The study involves 3,160 AF patients, all free of AF recurrence within 6 months to 1 year after ablation. Smart wearable monitors will track recurrence, and patients are followed for 24 months to assess event rates. Findings may reshape anticoagulation guidelines, improving clinical practice for AF patients worldwide.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Loop Recorder Detected High Rate of Atrial Fibrillation Recurrence after a Single Balloon- or Basket-Based Ablation of Paroxysmal Atrial Fibrillation: Results of the MACPAF Study. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Very long-term outcomes after a single catheter ablation procedure for the treatment of atrial fibrillation-the protective role of antiarrhythmic drug therapy. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Cryoballoon ablation of pulmonary veins for persistent atrial fibrillation: Results from the multicenter STOP Persistent AF trial. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

No Effect of Continued Antiarrhythmic Drug Treatment on Top of Optimized Pulmonary Vein Isolation in Patients With Persistent Atrial Fibrillation: Results From the POWDER-AF2 Trial. [2023]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Continuation of vitamin K antagonists as acceptable anticoagulation regimen in patients undergoing pulmonary vein isolation. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Complications of catheter ablation for atrial fibrillation: incidence and predictors. [2022]

7. United States 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. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Complications in pulmonary vein isolation in the Netherlands Heart Registration differ with sex and ablation technique. [2021]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of catheter ablation strategies for rhythm control in patients with atrial fibrillation: a meta-analysis. [2021]

10. United States 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. [2018]

11. Netherlands pubmed.ncbi.nlm.nih.gov

First data on cardiac mapping and outcome of pulmonary vein isolation using a novel ablation catheter with tip mini electrodes. [2019]