BOSTON—Results from the ARISTOTLE study showed that apixaban may give warfarin a run for its money, particularly for atrial fibrillation (AF); however, does the drug’s benefits differ between the varying types of AF? A secondary analysis of the ARISTOTLE trial, presented May 11 at a late-breaking clinical trial session at the 33rd annual scientific sessions of the Heart Rhythm Society, showed apixaban to take the cake in all subsets of AF patients when compared with warfarin.
“Although a few studies have a suggested a lower risk of stroke in patients with paroxysmal atrial fibrillation than those with persistent or permanent atrial fibrillation, a pooled analysis of the stroke prevention in atrial fibrillation trials demonstrated a comparable risk of stroke in paroxysmal and permanent atrial fibrillation,” said the study’s lead author, Sana Al-Khatib, MD, of the Duke Clinical Research Institute in Durham, N.C.
While stroke prevention guidelines make the same recommendations for all types of AF—paroxysmal, permanent and persistant—little is known about whether anticoagulant effects vary by type of AF.
To better understand these outcomes, Al-Khatib et al conducted a secondary analysis of the 18,201 patient ARISTOTLE trial to compare the risk of stroke or systemic embolism, major bleeding and all-cause mortality by AF type and treatment group between apixaban and warfarin.
ARISTOTLE researchers previously reported that apixaban (Eliquis, Bristol-Myers Squibb/Pfizer) was superior to warfarin in reducing the primary endpoint of stroke and systemic embolism. During the double-blind, double-dummy trial, patients received either 5 mg of apixaban twice daily or 2.5 mg BID or warfarin with an international normalized ratio (INR) target between two and three.
To classify AF type, clinical sites reported whether patients had persistent, permanent or atrial flutter at the time of study enrollment. “Interaction between the randomized treatment and type of AF was tested,” Al-Khatib said.
At study entry, 15.3 patients had paroxysmal AF and 84.7 percent of the cohort was reported to have persistent/permanent AF.
Al-Khatib noted that patients with persistent/permanent AF were older, had a longer time from first documented AF, higher CHADS2 scores and were more likely to have chronic heart failure.
“The risk of stroke or systemic embolism was significantly higher in patients with persistent or permanent atrial fibrillation compared with patients with paroxysmal AF,” she noted. Additionally, the researchers said that major bleeding rates did not statistically differ between the two groups. However, the rates of all-cause mortality tended to be higher in patients with persistent or permanent AF compared with those with paroxysmal AF.
“When we looked at the outcomes by type of AF and study treatment, we found that apixaban was superior to warfarin in reducing stroke and systemic embolism, major bleeding and all-cause mortality in both groups of patients,” she added.
While the results were promising, Al-Khatib said that a limitation to the analysis could be that the researchers were unable to analyze permanent and persistent AF separately. She noted that this could have introduced bias and noted that these two types of AF are “inherently different.”
“The effects of apixaban compared with warfarin were consistent among patients with paroxysmal and patients with persistent or permanent AF,” Al-Khatib summed. “Therefore apixaban is an attractive alternative to warfarin in patients with AF and at least one other risk factor for stroke and systemic embolism regardless of the time of AF.”
While apixaban is not yet approved by the FDA for this indication, if approved, it would join other anticoagulants, including dabigatran (Pradaxa), that are alternatives to warfarin in the AF patient population.