Prescription medications

Photo courtesy of the CDC

LONDON—Patients with atrial fibrillation (AF) who receive the anticoagulant rivaroxaban as stroke prophylaxis have low rates of major bleeding and stroke, according to real-world data from the XANTUS trial.

Investigators said this finding is similar to clinical trial results with rivaroxaban and suggest the drug is safe and effective for stroke prevention in patients with AF who have a high or low risk of thromboembolic events.

The team reported results of the XANTUS trial in the European Heart Journal and at the ESC Congress 2015 (abstract 5072). The study was sponsored by Bayer, the company developing rivaroxaban in cooperation with Janssen Pharmaceuticals, Inc.

“The findings reaffirm the positive benefit-risk profile of rivaroxaban established in the phase 3 clinical trial ROCKET AF, in which rivaroxaban was shown to provide effective stroke prevention with a similar overall bleeding profile and significantly lower rates of the most feared intracranial and fatal bleeds compared with vitamin K antagonists,” said John A. Camm, MD, of St. George’s University of London in the UK.

“The patients included in ROCKET AF were at moderate to high risk of stroke, with a mean CHADS2 score of 3.5, and the incidence of major bleeding in those taking rivaroxaban was 3.6 per 100 person-years. In XANTUS, patients seen in daily clinical practice had a lower risk of stroke, with a mean CHADS2 score of 2.0, and the incidence rate of major bleeding was lower, at 2.1 per 100 person-years.”

Patients and treatment

For the XANTUS trial, Dr Camm and his colleagues evaluated the outcomes of rivaroxaban use in 6784 patients with non-valvular AF who were treated at 311 centers across Europe and Canada in routine clinical practice.

Patients had newly diagnosed AF (18.5%), paroxysmal AF (40.6%), persistent AF (13.6%), and permanent AF (27%). For 0.2% of patients, data on their exact diagnosis was missing.

Comorbidities included hypertension (74.7%), diabetes mellitus (19.6%), prior stroke/non-central nervous system systemic embolism/transient ischemic attack (19%), congestive heart failure (18.6%), and prior myocardial infarction (10.1%).

The patients’ mean age was 71.5, and 37.2% were older than 75. Their mean CHADS2 score was 2, and their mean CHA2DS2VASc score was 3.4. A little more than half (54.5%) of patients were vitamin K agonist-naïve.

All treatment and dosing decisions for rivaroxaban were at the discretion of the treating physicians. Patients received the drug at 15 mg (n=1410), 20 mg (n=5336), or other doses (n=35).

They were followed for 1 year or until 30 days after premature treatment discontinuation. Bleeding events and major thromboembolic events were centrally adjudicated by an independent committee.

Results

By the end of the observation period, most patients (96.1%) had not experienced treatment-emergent major bleeding, all-cause death, or stroke/systemic embolism. And the majority of patients (80%) continued taking rivaroxaban throughout the 1-year study period.

The rate of stroke was 0.7% per year, and the annual rate of stroke/systemic embolism was 0.8%.

Overall, 2.1% of patients per year experienced treatment-emergent major bleeding. Non-major bleeding events occurred in 15.4% of patients per year.

The yearly rate of fatal bleeding was 0.2%, critical organ bleeding was 0.7%, intracranial hemorrhage was 0.4%, mucosal bleeding was 1.0%, and gastrointestinal bleeding was 0.9%. In addition, 0.9% of patients required transfusions of 2 or more units of packed red blood cells or whole blood per year.

The rate of on-treatment, all-cause mortality was 1.9% per year. There were 118 deaths in all, and some patients had multiple reasons reported as the cause of death. Causes of death were cardiovascular events (n=49), cancer (n=23), bleeding (n=12), infectious disease (n=10), other (n=16), and unexplained (n=9).

“These real-world insights from XANTUS complement and expand on what we already know from clinical trials and provide physicians with reassurance to prescribe rivaroxaban as an effective and well-tolerated treatment option for the broad range of patients with AF seen in their everyday clinical practice,” Dr Camm concluded.

Rivaroxaban appears safe, effective in the real world