Apixaban Prevents Stroke in A-fib Patients Irrespective of Previous Stroke/TIA

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The novel oral direct factor Xa inhibitor apixaban shows the same superior efficacy in preventing stroke compared with aspirin in patients with atrial fibrillation (A-fib) regardless of a history of stroke or transient ischemic attack (TIA). The results, in the March 2012 issue of Lancet Neurology, come from a subgroup analysis of a trial that was stopped early due to overwhelming evidence of the superiority of apixaban.

In the double-blind AVERROES (Apixaban Versus Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients who have Failed or are Unsuitable for Vitamin K Antagonist Treatment) trial, 5,599 patients were randomized to apixaban (5 mg twice daily) or aspirin alone (81-324 mg per day). For the prespecified subgroup analysis, researchers led by Hans-Christoph Diener, MD, of the University of Essen (Essen, Germany), looked at outcomes in patients with nonvalvular A-fib and a history of stroke or TIA.

Efficacy Across All Stroke Types

In Kaplan-Meier cumulative hazard analysis, the primary efficacy outcome of stroke or systemic embolism was more frequent at 1 year in the group with previous stroke or TIA compared with those with no such history (5.73 [95% CI 4.10-8.02] vs. 2.36 [95% CI 1.93-2.89]). The same pattern was seen for all other vascular outcomes except MI.

However, just as in the overall study, specifically among patients with previous stroke or TIA, those treated with apixaban showed a consistently lower rate of all stroke types compared with those who received aspirin (table 1).

Table 1. One-Year Stroke Rates in Patients with Prior History

 

Major bleeding, the primary safety outcome, was more frequent in patients with history of previous stroke or TIA than in patients without any history (HR 2.88; 95% CI 1.77-4.55; P < 0.001). The effect of apixaban vs. aspirin for bleeding complications was consistent in the 2 subgroups, with no interaction.

According to the study authors, for patients with previous stroke or TIA, 6.4 strokes or systemic embolic events would be prevented per 100 patients treated for 1 year on apixaban vs. aspirin, resulting in a number needed to treat of 16 (95% CI 10-36). For patients without previous stroke or TIA, the corresponding number of prevented primary outcome events would be 1.4, resulting in a number needed to treat of 74 (95% CI 44-241).

Relevant for Clinical Practice

Dr. Diener and colleagues observe that the risk of the most feared complication of anticoagulant therapy, hemorrhagic stroke, with apixaban “was similar to that with aspirin in patients with and without previous stroke or TIA. Therefore, our results are relevant for clinical practice as patients with atrial fibrillation with history of stroke or TIA, who are at higher risk for recurrent events, experience a substantial reduction in ischemic strokes with apixaban, without an excess in hemorrhagic stroke,” they write.

Moreover, the findings reinforce the tolerability of apixaban showing a profile of adverse events similar to that of aspirin, the authors say.

Although they acknowledge that the small number of patients in the trial with prior history of stroke or TIA is a major limitation of the analysis, the study authors say AVERROES is the “biggest trial comparing a new anticoagulant with aspirin in patients with atrial fibrillation” and argue that apixaban “should be considered for the prevention of stroke or systemic embolism when treating patients not suitable for vitamin K antagonist therapy.”

Optimism Tinged with Caution

In an editorial accompanying the study, Mahesh P. Kate, MD, and Ashfaq Shuaib, MD, both of the University of Alberta Hospital (Alberta, Canada), write that “the superior efficacy and similar safety of apixaban with respect to aspirin in the subgroup of AVERROES trial patients is good news.”

In fact, they suggest that given the significantly better medication profile of newer agents like apixaban, dabigatran, and rivaroxiban, “higher cost might be the only significant factor that keeps vitamin K antagonists and aspirin as treatment alternatives for stroke prevention in atrial fibrillation.”

The study authors add that it is hoped that appropriate use of the newer agents “will lead to a major reduction in risk of stroke in patients with nonvalvular atrial fibrillation and a history of previous stroke or TIA.”

 

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Sources:
1. Diener H-C, Eikelboom J, Connolly SJ, et al. Apixaban versus aspirin in patients with atrial fibrillation and previous stroke or transient ischemic attack: A predefined subgroup analysis from AVERROES, a randomized trial. Lancet Neurol. 2012;Epub ahead of print.

2. Kate MP, Shuaib A. Prevention of stroke in atrial fibrillation: Cautious optimism. Lancet Neurol. 2012;Epub ahead of print.

3. Connolly SJ, Eikelboom J, Joyner C, et al. Apixaban in patients with atrial fibrillation. N Engl J Med. 2011; 364:806-817.

 

 

Related Stories:

• Apixaban Bests Warfarin in Stroke Prevention for Atrial Fib
• Apixaban Increases Major Bleeding in High-Risk ACS Patients
• ARISTOTLE Makes Its Case: Apixaban Noninferior to Warfarin in A-fib

 

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