Apixaban Cuts Stroke Risk in All Types of AF, Says ARISTOTLE

May 16, 2012

May 16, 2012 (Boston, Massachusetts) — The primary conclusion of the ARISTOTLE trial, that the direct factor Xa inhibitor apixaban (Eliquis, Pfizer/Bristol-Myers Squibb) is better than warfarin at preventing stroke or systemic embolism in patients with atrial fibrillation (AF), applies regardless of whether AF is paroxysmal or either permanent or persistent [1].

That's from a prospectively planned secondary analysis of the trial that also shows that apixaban lowers the risk of bleeding complications better than the older anticoagulant in both types of AF. It was presented here last week at the Heart Rhythm Society 2012 Scientific Sessions by Dr Sana Al-Khatib (Duke Clinical Research Institute, Duke University, Durham, NC). Entry into ARISTOTLE called for AF plus at least one other stroke/embolism risk factor.

The analysis also showed a difference in embolic risk by type of AF regardless of treatment. Much of the data until now, she told heartwire , suggest that "the outcomes of patients with persistent or permanent atrial fibrillation and paroxysmal atrial fib are similar with respect to stroke or systemic embolism. Our results actually challenge that view, because they clearly show that people with persistent or permanent AF have a higher risk of stroke or systemic embolism, and that was the case even when we adjusted for possible confounders."

ARISTOTLE randomized 18 201 patients with AF and at least one other stroke risk factor to receive apixaban at 5 mg twice daily or warfarin to a target INR of 2.0 to 3.0. As covered extensively by heartwire , apixaban led to a 21% reduction in the relative risk of stroke or systemic embolism (p=0.011), a 31% reduction in bleeding (p<0.001), and an 11% reduction in all-cause mortality (p=0.047) over a mean of 1.8 years, compared with warfarin.

In the current analysis, 2786 patients (15.3%) had paroxysmal AF and 15 412 (84.7%) had persistent/permanent AF. The latter were older, more often male, and had a slightly but significantly higher CHADS2 score than the former.

The superiority of apixaban over warfarin for stroke or systemic embolism in the overall trial was replicated across the two types of AF, with the p value for interaction between apixaban and AF type at 0.71. The interaction p value for major bleeding was 0.50, for all-cause mortality was 0.75, and for the composite of stroke, systemic embolism, major bleeding, and all-cause mortality was 0.62.

Independently of treatment, those with paroxysmal AF, compared with those who had persistent/permanent AF, had a lower rate of stroke or systemic embolism (2.2% vs 3.5% per 100 patient-years of follow-up) with an adjusted hazard ratio (HR) of 0.70 (95% CI 0.51–0.93, p=0.015). No such significant differences were seen between the two AF types with respect to rate of major bleeding and all-cause mortality.

One implication of the findings: if apixaban is under consideration as an alternative to warfarin in a patient with AF, apixaban's appeal shouldn't necessarily vary from one type of AF to the other.

"Although in our study we show that patients with paroxysmal atrial fib are at a lower risk of stroke or systemic embolism, given all the favorable effects of apixaban, especially on the safety end points," Al-Khatib said, "it may be a good idea to put people on apixaban regardless of the type of atrial fib, if they have at least one other risk factor for stroke or system embolism."

Al-Khatib discloses receiving research grants from Bristol-Myers Squibb. Disclosures for the coauthors are listed in the abstract.

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