JACC in a Flash | In patients with atrial fibrillation (AF), anticoagulation strategies must be carefully selected—taking into consideration the risk of bleeding and thromboembolic events and the interaction with potential treatments to correct cardiac arrhythmias. Three novel oral anticoagulant (NOAC) drugs have been approved for stroke prevention in these patients over the last few years, each demonstrating at least a level of noninferiority to warfarin, the old standard. Two new studies published in JACC evaluated the risk of complications with rivaroxaban or apixaban therapy, compared to warfarin, during and after procedures to correct AF-related arrythmias.

Rivaroxaban Versus Warfarin

In the first, primary co-authors Dhanunjaya Lakkireddy, MD, and Yeruva Madhu Reddy, MD, from the Blood Heart Rhythm Center at University of Kansas Hospital in Kansas City, performed a multicenter, observational study from a prospective registry of patients undergoing AF ablation in eight centers across the United States. A total of 642 patients were included in the study—321 had uninterrupted preiprocedural rivaroxaban, and an equal number received uninterrupted warfarin therapy.

Mean age of all participants was 63±10 years, and 328 (51%) had paroxysmal AF (with an equal distribution between groups). Patients in the warfarin-treated group did have a slightly higher mean HAS BLED score.

Bleeding and embolic complications occurred in 4 (7.3%) and 2 (0.3%) patients, respectively, both of which were transient ischemic attacks (TIAs). During the first 30 days post-procedure, there was no major difference in complications between the rivaroxaban and warfarin groups, respectively:

• major bleeding complications: 5/1.6% vs. 7/1.9% (p = 0.772)
• minor bleeding complications: 16/5.0% vs. 19/5.9% (p = 0.602)
• embolic complications: 1/0.3% vs. 1/0.3% (p = 1.0)

"Increasingly more patients are being treated with newer oral anticoagulants, thereby complicating the periprocedural anticoagulation management," Dr. Lakkireddy and colleagues wrote. Although warfarin is the standard anticoagulation protocol for AF patients, uninterrupted warfarin does not eliminate the risk of complications. In the current study, 7/321 (2%) patients ended up having subtherapeutic international normalized ratios on the morning of the procedure, despite being on uninterrupted warfarin and having a close outpatient follow-up; moreover, one of those seven patients had a TIA after the procedure, necessitating additional anticoagulation.

With its once-a-day dosing regimen and proven efficacy, rivaroxaban is a potentially attractive alternative to warfarin, especially considering the "very reassuring" safety results from the current study. There is no specific antidote for life-threatening hemorrhagic complications in patients on rivaroxaban, so concerns about reversal of anticoagulation still exist, the authors noted.

Apixaban Versus Warfarin

In the second study, Greg Flaker, MD, from the University of Missouri in Columbia, and colleagues conducted a post-hoc analysis of patients undergoing cardioversion in the ARISTOTLE trial, which compared warfarin with apixaban in reduction of thromboembolic events in AF patients. Previous studies have shown a lower risk of these events with warfarin and dabigatran, but there is no definitive evidence regarding apixaban after cardioversion.

A total of 743 cardioversions were performed in 540 patients: 265 first cardioversions in patients assigned to apixaban and 275 in those receiving warfarin. Most patients (414) only underwent a single cardioversion, 87 underwent two, and 39 underwent three or more. The mean duration of anticoagulation prior to cardioversion was 243±231 days for patients on warfarin and 251±248 days for patients on apixaban.

As seen in the TABLE, the rates of major clinical events (including stroke, systemic embolism, myocardial infarction [MI], major bleeding, and death) were comparable between warfarin and apixaban. Notably, neither stroke nor systemic embolism was observed.

TABLE. Clinical Outcomes within 30 Days after any Cardioversion
Outcome	Warfarin (n = 412)	Apixaban (n = 331)	Total (n = 743)
Stroke or systemic embolism	0	0	0
Myocardial infarction	1 (0.2%)	1 (0.3%)	2 (0.2%)
Major bleeding	1 (0.2%)	1 (0.3%)	2 (0.2%)
Death	2 (0.5%)	2 (0.6%)	4 (0.9%)

In addition to apixaban's noninferiority to the old standard, warfarin, Dr. Flaker and co-authors noted some other advantages of the newer anticoagulant, including time to effect: "It may take 2 or more months to achieve adequate anticoagulation for cardioversion with warfarin. Because effective anticoagulation is achieved more quickly with new oral anticoagulants than with warfarin, a hypothetical advantage is that the new anticoagulants may shorten the pretreatment time needed for adequate anticoagulation before cardioversion."

While these results are reassuring, the minimum duration of therapy required to assure a low risk of an embolic event remains unknown. "Until additional data are reported, elective cardioversion of AF could be performed with a low risk of stroke or systemic emboli in patients treated chronically with new oral anticoagulants," the authors concluded.

Flaker G, Lopes RD, Al-Khatib SM, et al. J Am Coll Cardiol. 2013 October 26. [Epub ahead of print]
Lakkireddy D, Reddy YM, Di Biase L, et al. J Am Coll Cardiol. 2013 December 23. [Epub ahead of print]

Keywords: International Normalized Ratio, Registries, Stroke, beta-Alanine, ACC Publications, CardioSource WorldNews

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