Xarelto works in new cardioversion indication for AF

Bayer and Janssen's novel oral anticoagulant (NOAC) Xarelto can be used in place of warfarin in atrial fibrillation patients undergoing cardioversion to restore normal heart rhythm, according to a new study.

Xarelto (rivaroxaban) is the first of the NOACs to show a benefit in this setting and - in addition to being more practical to administer to patients - also seemed to have an advantage over vitamin K antagonists (VKAs) such as warfarin, according to the results of the X-VErT study.

Cardioversion is a common medical procedure performed on patients with atrial fibrillation in order to reset the heartbeat back to a regular sinus rhythm.

Current guidelines recommend at least three weeks of treatment with VKAs prior to elective cardioversion in order to achieve adequate anticoagulation and reduce the risk of complications such as stroke, but X-VErT showed that Xarelto's rapid onset of action meant it could be administered for just one week with equal safety and efficacy.

Compared to warfarin, the NOAC does not require dose-matching to the patient, is given just once a day and does not require regular blood clotting tests, making it an attractive, practical alternative to VKAs in this setting, according to the trial investigators.

Co-principal investigator Riccardo Cappato said whilst presenting the data at the European Society of Cardiology (ESC) meeting in Barcelona that the shorter time to cardioversion could be a major benefit, although he added that this was not a specified outcome in the study so the finding "should be interpreted with caution."

Patients scheduled for cardioversion have to delay or cancel the procedure if their clotting tests do not indicate good anticoagulation levels, and the complexities involved in dosing drugs like warfarin can make it hard to reach treatment goals.

X-VErT enrolled around 1,500 patients who were assigned to either Xarelto 20mg once-daily or a VKA (mainly warfarin) and found that compared to patients treated with Bayer and Janssen's drug had a similar risk of stroke or transient ischaemic attack, peripheral embolism, myocardial infarction and cardiovascular death, at 0.5% and just over 1%, respectively.

Without adequate anticoagulation, AF patients undergoing cardioversion have a risk of thromboembolic complications with stroke rates of 5%-7%. There was also no difference between the groups in the number of major bleeding incidences.

While X-VErT zeroes in on a specific application for Xarelto, the trial is part of a massive clinical programme undertaken by Bayer and Janssen as they jostle for position in the market alongside rival NOACs Eliquis (apixaban) from Pfizer and Bristol-Myers Squibb and Boehringer Ingelheim's Pradaxa (dabigatran).

Xarelto racked up sales of more than $2bn last year in its current indications, but Johnson & Johnson (J&J) subsidiary Janssen and Bayer are investing heavily in a 275,000-patient programme - called EXPLORER - to expand the use of the drug.

The partners have just announced new trials in acute coronary syndrome (ACS) - the FDA turned down three prior bids to break into that patient category although it is approved for ACS in Europe and elsewhere - as well as embolic stroke of undetermined source (ESUS) and peripheral artery disease (PAD).

Analysts have suggested peak sales of NOACs could reach several billion dollars a year, and while Xarelto had first-to-market advantage and a lead over its rivals in terms of market share, Bayer and Janssen want to claim as much of that opportunity as possible.