In catheter ablation of AF, continuing vs interrupting warfarin reduced periprocedural thromboembolic events

Di Biase L, Burkhardt JD, Santangeli P, et al. Periprocedural stroke and bleeding complications in patients undergoing catheter ablation of atrial fibrillation with different anticoagulation management: Results from the Role of Coumadin in Preventing Thromboembolism in Atrial Fibrillation (AF) Patients Undergoing Catheter Ablation (COMPARE) randomized trial. Circulation. 2014;129:2638-44.

Clinical impact ratings: C ★★★★★✩✩ H ★★★★★★✩ Question

Main results

In patients having catheter ablation for atrial fibrillation (AF), does continuing warfarin reduce periprocedural thromboembolic and hemorrhagic events compared with interrupting warfarin?

Continuing warfarin reduced risk for periprocedural thromboembolic events and minor bleeding compared with interrupting warfarin; groups did not differ for major bleeding or pericardial effusion (Table).

Methods Design: Randomized controlled trial (Role of Coumadin in Preventing Thromboembolism in Atrial Fibrillation Patients Undergoing Catheter Ablation [COMPARE] trial). NCT01006876. Allocation: {Concealed}*.† Blinding: Blinded† (primary outcome assessors and {data and safety monitoring committee}*).

Conclusion In patients having catheter ablation for atrial fibrillation, continuing warfarin reduced periprocedural thromboembolic events at 48 hours compared with interrupting warfarin. *Information provided by author. †See Glossary.

Follow-up period: 48 hours.

Source of funding: No external funding.

Setting: {7 centers in the USA and Italy}*.

For correspondence: Dr. A. Natale, Texas Cardiac Arrhythmia Institute, Austin, TX, USA. E-mail [email protected]

Patients: 1584 patients ≥ 18 years of age (mean age 62 y, 75% men) with AF, who were receiving warfarin and scheduled for ablation, had an international normalized ratio (INR) of 2.0 to 3.0 in the past 3 to 4 weeks, and had a CHADS2 score ≥ 1. Exclusion criteria included bleeding disorders, inherited thrombophilic disorder, prosthetic heart valves, or use of oral contraceptives or estrogen replacement therapy. Intervention: Continuous use of warfarin, with bolus unfractionated heparin (10 000 IU for men and 8000 IU for women) before transseptal puncture, and maintenance of activated coagulation time (ACT) > 300 s during procedures (n = 794); or discontinuation of warfarin 2 to 3 days before ablation and low-molecular-weight heparin bridging, heparin bolus,15 000 IU, before transseptal puncture, continuous heparin infusion adjusted to maintain ACT > 350 s during procedures, and a single dose of aspirin, 325 mg, after ablation (n = 790). In the continuing warfarin group, patients with an INR > 3.5 on the day of ablation were excluded; those with an INR 3.0 to 3.5 were given fresh-frozen plasma before ablation. Outcomes: Primary outcome was thromboembolic events (stroke, transient ischemic attack, or systemic thromboembolism). Other outcomes included major bleeding, minor bleeding, and pericardial effusion. Patient follow-up: {100%}*. Continuing vs interrupting warfarin in patients having catheter ablation for AF‡ Outcomes

Continuing Interrupting At 48 h after catheter ablation warfarin warfarin RRR (95% CI) NNT (CI)

Periprocedural thromboembolic events§


Major bleeding


Minor bleeding


Pericardial effusion



95% (79 to 99)

22 (21 to 26)


63% (−29 to 89)

Not significant

22% 0.89%

81% (73 to 87)

6 (5 to 7)

43% (−81 to 82)

Not significant

‡AF = atrial fibrillation; other abbreviations defined in Glossary. RRR, NNT, and CI calculated from relative risks (where reported) and event rates in article. §Stroke (0.25% vs 3.7%, P < 0.001), transient ischemic attack (0% vs 1.3%, P < 0.001), or systemic thromboembolism (0 events). ||Corrected event rates confirmed by author.

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Commentary Catheter ablation for the management of AF is now one of the most frequently performed procedures in the electrophysiology laboratory, and thromboembolism is one of the most devastating complications of this procedure. To reduce periprocedural bleeding, the conventional and widely adopted approach has been to withhold anticoagulation with warfarin and use low-molecularweight heparin to bridge the gap in anticoagulation before and after ablation. In the first multicenter randomized trial to compare uninterrupted anticoagulation with the conventional approach, Di Biase and colleagues showed the superiority of uninterrupted anticoagulation for reducing thromboembolism without increasing complications. Maintaining anticoagulation with warfarin around the time of the procedure was not associated with increased major bleeding, and minor bleeding was reduced. What makes the study by Di Biase and colleagues so important is that it includes “real-world” patients presenting for catheter ablation. The implications of the study are important from both patient safety and economic perspectives. Further, although not directly assessed, maintaining anticoagulation may allow patients to safely forgo transesophageal echocardiography without increasing the risk for thromboembolism. The findings of Di Biase and colleagues are consistent with those of Birnie and colleagues (1) and will probably be widely adopted. However, clinicians implementing a similar strategy should adopt the same measures used by this group to enhance safety, such as excluding patients with an INR > 3.5 and using fresh-frozen plasma for those with an INR of 3.0 to 3.5. The primary implication is that, when managed carefully, continuing warfarin is superior to “bridging” for preventing periprocedural thromboembolism and has an acceptably low risk for bleeding. Munther K. Homoud, MD Tufts Medical Center Boston, Massachusetts, USA Reference 1. Birnie DH, Healey JS, Wells GA, et al; BRUISE CONTROL Investigators. N Engl J Med. 2013;368:2084-93.

16 December 2014 | ACP Journal Club | Volume 161 • Number 12

In catheter ablation of AF, continuing vs interrupting warfarin reduced periprocedural thromboembolic events.

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