I have just returned from the Heart Rhythm Society meeting in Denver, CO. The meeting was heavily focused on surgical and device implantation procedures, and particularly around anticoagulation in the peri-procedural setting. Two of the studies presented during the first late-breaking clinical trials session were focused on this issue.
The first, the COMPARE trial (Di Biase et al), demonstrated that catheter ablation procedures performed without discontinuation of warfarin had statistically fewer peri-procedural strokes and bleeding complications. This finding could result in a change in clinical practice, as warfarin-treated patients undergoing ablation would typically have their warfarin discontinued and would receive bridging therapy with intravenous heparin or a low-molecular weight heparin.
The second trial, the BRUISE CONTROL trial (Birnie et al), investigated uninterrupted warfarin therapy in patients undergoing either pacemaker or implantable defibrillator surgery, compared to the guideline-recommended cessation of warfarin therapy to bridging with heparin. The trial was terminated early due to the uninterrupted warfarin arm achieving the primary outcome of reduced clinically significant hematoma.
These trials may be expected to result in significant changes in clinical practice. Operative procedures such as ablation or device implantation should no longer require warfarin discontinuation. Discontinuation of warfarin for operative procedures has opened the door to physicians to switch to treatment with the novel oral anticoagulants in the post-operative period. Therefore it could be expected from these findings that currently-treated warfarin patients will remain on warfarin.
Another factor suggesting that there may still be life in warfarin is the lack of guidelines surrounding management of anticoagulation in the peri-procedural setting with the novel anticoagulants. While two abstracts presented at the meeting demonstrated that both rivaroxaban and dabigatran were comparable to uninterrupted warfarin in the peri-procedural setting, the current lack of guidelines surrounding their use in this setting, as well as an inability to determine anticoagulation levels and a lack of reversal agents in the event of bleeding, continues to give warfarin an advantage within this patient group.
The best evidence that life remains in warfarin within the anticoagulation market came from a spirited debate between Drs. Ezekowitz and Camm in a ?Battle of the Titans?. While Dr. Ezekowitz provided ample evidence supporting the efficacy of the novel oral anticoagulants, this evidence was specific to the patient populations in which they are approved. Dr. Camm vociferously reminded the audience that there are many areas of rhythm management in which warfarin remains the primary treatment option for stroke prevention; for example, patients with valvular AF, or with mechanical valves.
Another point that Dr. Camm raised is that despite the positive findings surrounding the new agents, a careful analysis of the data is required. For example, as Wallentin et al demonstrated (Lancet, 2010), warfarin proved as effective as dabigatran when the time in therapeutic range (TTR) was greater than 72.6% (similar to TTR values in the UK among other nations).
The point to this blog is not to denigrate the novel oral anticoagulants, which very clearly represent a major development in the treatment of AF and VTE, and are rightly expected to cannibalize the current anticoagulation market. However, what is apparent is that until these agents increase the range of indications for which they are available, and until a greater clarity of data surrounding their use in the peri-procedural operative setting is available, the long-heralded end of warfarin that these agents were expected to achieve will be postponed for a little while longer.