NEW YORK - In patients with atrial fibrillation (AF) and a wide range of renal function, compared to warfarin, treatment with apixaban reduces the risk of cardiovascular events, according to multinational investigators.
As Dr. Ziad Hijazi told Reuters Health by email, "Renal dysfunction is a complex issue in patients with atrial fibrillation when balancing the risk of stroke versus the risk of bleeding."
"This study," he added, "shows that apixaban, compared with warfarin, was associated with a lower risk of stroke, death, and major bleeding, regardless of changes in renal function over time. These findings may aid clinicians in the treatment decision."
In a June 15 online paper in JAMA Cardiology, Dr. Hijazi, of Uppsala University Hospital, Sweden, and colleagues report that they came to this conclusion after examining data from a clinical trial (ARISTOTLE) on more than 16,800 AF patients randomized to apixaban or warfarin.
Over the course of a year, about a quarter (26%) maintained good renal function. Renal function declined in the others, and 13.6% showed a drop of more than 20%. The decline in renal function was more rapid in patients who were older or had comorbidities.
Overall, the risks of stroke or systemic embolism, major bleeding, and mortality were greater in patients with worsening renal function (hazard ratio, 1.53 for stroke or systemic embolism, 1.56 for major bleeding, and 2.31 for mortality).
However, such patients on apixaban, compared with warfarin, consistently demonstrated a lower relative risk of stroke or systemic embolism (HR 0.80), ischemic or unspecified stroke (HR 0.88), and major bleeding (HR 0.76).
In fact, as well as showing benefit in this group of patients, the researchers conclude, "The superior efficacy and safety of apixaban as compared with warfarin were similar in patients with normal, poor, and worsening renal function."
Commenting on the findings by email, cardiologist Dr. Anil Pandit of Scottsdale, Arizona, told Reuters Health, "The study by Hijazi et al answers very important clinical questions regarding safety and efficacy of apixaban in situations of declining renal function, a common phenomenon in a real world scenario."
An earlier meta-analysis, in which Dr. Pandit was involved, found decreased risk of major bleeding with apixaban in mild to moderate renal impairment when compared with other anticoagulants (warfarin, aspirin, and Lovenox) as a group.
"The main criticism of the findings of our meta-analysis was inapplicability in the real world scenario, where subclinical episodes of acute kidney injury and worsening renal failure, may lead to increased anticoagulant effect and bleeding," Dr. Pandit said. This new study "exactly answers this question in a large patient population, providing sustained evidence that apixaban is safe and effective in mild to moderate renal impairment patients."
"However," Dr. Pandit concluded, "one should keep in mind limitations of the retrospective data." He also pointed out that "the efficacy and safety of apixaban is not established in patients with severe renal failure, ... as this group of patients was not studied in the ARISTOTLE trial."
Bristol Myers Squibb and Pfizer funded the ARISTOTLE trial. Ten coauthors reported disclosures.
SOURCE: http://bit.ly/28LbKlt JAMA Cardiol 2016.