Apixaban Comparable to Warfarin for A-fib Patients Undergoing Cardioversion

Download this article's Factoid (PDF & PPT for Gold Subscribers)

Early stroke and systemic embolism rates in patients following cardioversion for atrial fibrillation (A-fib) are low and comparable between those receiving warfarin or the novel oral anticoagulant apixaban, according to a substudy of the ARISTOTLE trial published online November 6, 2013, ahead of print in the Journal of the American College of Cardiology. 

In the main trial, which randomized more than 18,000 patients with A-fib and at least 1 stroke risk factor to apixaban (5 mg twice daily) or warfarin (target INR 2.0-3.0), the factor Xa inhibitor reduced the incidence of stroke or systemic embolism, the primary outcome, as well as major bleeding and all-cause death.

In a post hoc analysis, Greg Flaker, MD, of the University of Missouri (Columbia, MO), and colleagues looked specifically at 540 patients who underwent cardioversion, 265 (331 procedures) from the apixaban arm and 275 (412 procedures) from the warfarin arm. Baseline characteristics including cardiac risk factors, type of A-fib, and CHADS2 scores were similar between groups.

Drugs Equally Safe, Effective

At 30 days postprocedure, no stroke or systemic embolism, the primary outcome, had occurred in either anticoagulant group. Rates of MI and death were very low and similar between arms, as was the incidence of major bleeding (table 1).

Table 1. Clinical Outcomes at 30 Days


(n = 275)

(n = 265)

   Stroke or Systemic Embolism









   Major Bleeding



A separate analysis of the 451 patients who remained on study medication for cardioversion (n = 86 for apixaban, n = 85 for warfarin) showed a similar pattern.

Data Reassuring 

“Our data are reassuring in that cardioversion can be performed safely in apixaban-treated patients,” Dr. Flaker told TCTMD in an email communication. 

Michael D. Ezekowitz, MD, PhD, of Thomas Jefferson Medical College (Philadelphia, PA), agreed, noting that event rates in patients on long-term anticoagulation with either drug prior to cardioversion were “low, which is very good.”  Moreover, he told TCTMD in a telephone interview, event times between the two drugs are “practically identical in patients who have been anticoagulated for a long period of time prior to cardioversion.”

Dr. Ezekowitz observed that post-hoc analyses from the randomized RE-LY trial evaluating dabigatran and the ROCKET-AF trial assessing rivaroxaban found that these novel oral anticoagulants also had event rates similar to warfarin when used before cardioversion in A-fib patients.  

In an editorial accompanying the paper, Matthew R. Reynolds, MD, MSc, of the Harvard Clinical Research Group (Boston, MA), concluded that, based on the current study as well as data from RE-LY and ROCKET-AF, patients “who have been treated with a [novel oral anticoagulant] for months and seem reliable with respect to adherence” do not need to be switched to warfarin before cardioversion.

Possible Advantages of Apixaban

Dr. Flaker and colleagues noted that “because effective anticoagulation is achieved more quickly with new oral anticoagulants than with warfarin, a hypothetical advantage is that they “may shorten the pretreatment time needed for adequate anticoagulation before cardioversion.”

Overall, potential advantages of apixaban are “shorter half-life, lack of need for monitoring, and reduced bleeding risk with improved efficacy compared with warfarin,” Dr. Flaker said, adding that apixaban also has fewer drug interactions.

Further Research Needed

However, the current analysis does not show the experience of patients requiring cardioversion for newly diagnosed persistent A-fib, Dr. Ezekowitz observed. These patients are usually administered short-term intravenous or subcutaneous heparin with simultaneous warfarin for anticoagulation before cardioversion, he said. This approach has not been compared with apixaban, which does not require heparin bridging due to its rapid onset of action, he explained. 

In addition, further research is needed to determine the minimal amount of time patients must be on apixaban prior to cardioversion and whether transesophageal echocardiography is required to determine whether the patient has left A-fib, Dr. Ezekowitz added.

Study Details

Three quarters of cardioversion procedures were performed during the first year. The mean time to first cardioversion was 243 ± 231 days for warfarin patients and 251 ± 248 days for individuals on apixaban. 

Prior to cardioversion, patients received a minimum of 4 days warfarin and 1 day of apixaban treatment. Eighty percent of individuals randomized to warfarin were taking the study drug at cardioversion compared to 84% of participants assigned to apixaban.


1. Flaker G, Lopes RD, Al-Khatib SM.. Efficacy and safety of apixaban in patients following cardioversion for atrial fibrillation: Insights from the ARISTOTLE trial. J Am Coll Cardiol. 2013;Epub ahead of print.

2. Reynolds MR. Cardioversion with novel oral anticoagulants: Reconfirming a 50-year-old standard. J Am Coll Cardiol. 2013;Epub ahead of print.




Related Stories:

  • Dr. Flaker reports receiving grants from Boehringer Ingelheim and Sanofi-Aventis and consulting fees from Bristol-Myers Squibb, Boehringer Ingelheim, and Sanofi-Aventis.
  • Dr. Ezekowitz reports receiving consulting fees from Bayer/Johnson & Johnson,  Boehringer Ingelheim, Bristol-Myers Squibb/Pfizer, and Daiichi Sankyo.
  • Dr. Reynolds reports no relevant conflicts of interest.

We Recommend