AFib Ablation on "Therapeutic Warfarin" - COMPARE Trial: Clinical Implications and Future Directions

Periprocedural iatrogenic thromboembolic events such as TIA and STROKE represent the most insidious complications of radiofrequency catheter ablation of atrial fibrillation (AF).1–5 The periprocedural anticoagulation management plays an important role to minimize these complications.

The AF ablation consensus document still suggest an anticoagulation management with warfarin discontinuation three to five days before ablation, followed by periprocedural bridging with low-molecular weight heparin, although the possibility of performing such procedures without warfarin discontinuation is also suggested.1-3

Observational data suggest that performing radiofrequency catheter ablation of atrial fibrillation (AF) without warfarin discontinuation, reduce the periprocedural risk of thromboembolic events, when compared to approaches that discontinue warfarin prior to procedures.4,5

Although clear consistent evidence from observational studies and metanalysis exists, no randomized study has been performed. The COMPARE Trial (NCT01006876 is the first open-label, randomized, parallel-group, multicenter study comparing AF ablation procedures performed with and without warfarin discontinuation. The study enrolled 1584 patients (18 to 75 years of age) with non valvular atrial fibrillation who were at high risk of thromboembolic events with well-managed warfarin levels in the six to eight weeks prior to enrollment. The majority of enrolled patients had long standing persistent AF (around 50% of the population in both groups) and had high CHADS2 score >2 in 70%.

Importantly, patients with CHADS2 score of zero were excluded. In both groups heparin was administered to keep the ACT above 300 seconds.

Group 1 patients (off warfarin; n=790) discontinued warfarin two to three days prior to ablation and were bridged with low weight molecular Heparin (LWMH) while Group 2 patients (on warfarin; n=794) received warfarin therapy throughout the study as well as heparin during the entire procedure.

Neurological and bleeding complications were assessed 48 hours after ablation in both groups. The primary endpoint was the incidence of thromboembolic (TE) events 48 hours post ablation. The incidence of periprocedural events was 4.9% (n=39) in Group 1 (off warfarin) and two (0.25%) patients had stroke in Group 2, (on warfarin) p<0.001; interestingly 26 out of 29 strokes in group 1 (off Coumadin) of the events occurred in LSP AF patients. In Group 2, (on warfarin) both patients had LSP AF and had a subtherapeutic INR the day of the procedure.

No significant difference in major bleeding and pericardial effusion was seen between groups while a significant higher number of patients had minor bleeding (especially groin hematoma) in Group 1 (off warfarin 22%) when compared to Group 2 (on warfarin 4.1%) (p<0.001). Warfarin use during ablation for AF was associated with relative risk reduction of 95% for stroke/TIA, and 81% for minor bleeding.

At the multivariate analysis, warfarin discontinuation, high CHADS2 score, and AF type (non paroxysmal) were significant predictors of TE events.

The study concluded that performing catheter ablation of atrial fibrillation without warfarin discontinuation significantly reduced the occurrence of periprocedural stroke and bleeding complications.

The risk of these complications during AF ablation is predominantly confined to pts with non paroxysmal AF. Therefore, future studies assessing the protecting value of newer oral anticoagulants (dabigratan, rivaroxaban apixaban and edoxaban) should be performed in comparison with on warfarin treatments and especially in patients with non paroxysmal AF since in paroxysmal pts these events are less frequent.

Observational and conflicting data comparing dabigratan to the on warfarin approach are present in the literature.6,7,8 However, it is fair to say that most of these studies discontinued the newer anticoagulant before the procedure and included mostly patients with paroxysmal AF. In addition, while it appears safe to manage complications on therapeutic INR, it is unclear whether the same is true for the newer oral anticoagulants in view of the lack of a reversal agent. In the future more studies will test the safety of periprocedural treatment with the newer anticoagulants. It is important that such studies include high risk patients before they are given a "clean bill of health."


  1. Calkins H, Brugada J, Packer DL, et al. HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for personnel, policy, procedures and follow-up. A report of the Heart Rhythm Society (HRS) Task Force on catheter and surgical ablation of atrial fibrillation. Heart Rhythm 2007; 4:816–861.
  2. Cappato R, Calkins H, Chen SA, et al. Updated worldwide survey on the methods, efficacy, and safety of catheter ablation for human atrial fibrillation. Circ Arrhythm Electrophysiol 2010;3:32–38.
  3. Natale A, Raviele A, Arentz T, et al.. Venice Chart international consensus document on atrial fibrillation ablation. J Cardiovasc Electrophysiol 2007;18:560 –580.
  4. Di Biase L, Burkhardt JD, Mohanty P, et al. Periprocedural stroke and management of major bleeding complications in patients undergoing catheter ablation of atrial fibrillation: the impact of periprocedural therapeutic international normalized ratio. Circulation 2010;121:2550 –255.
  5. Santangeli P, Di Biase L, Horton R, et al. Ablation of atrial fibrillation under therapeutic warfarin reduces periprocedural complications: evidence from a meta-analysis. Circ Arrhythm Electrophysiol 2012;5:302-11
  6. Lakkireddy D, Reddy YM, Di Biase L, et al. Feasibility and safety of dabigatran versus warfarin for periprocedural anticoagulation in patients undergoing radiofrequency ablation for atrial fibrillation: results from a multicenter prospective registry. J Am Coll Cardiol 2012;59:1168-74.
  7. Kim JS, She F, Jongnarangsin K, et al. Dabigatran vs warfarin for radiofrequency catheter ablation of atrial fibrillation. Heart Rhythm 2013 ;10:483-9.
  8. Winkle RA, Mead RH, Engel G, Kong MH, Patrawala RA. The use of dabigatran immediately after atrial fibrillation ablation. J Cardiovasc Electrophysiol 2012;23:264-8.

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