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February 10th, 2011

Apixaban Better Than Aspirin for Stroke Prevention in AF Patients Unable to Take Warfarin

A new trial presented at the American Stroke Association’s International Stroke Conference and published online in the New England Journal of Medicine demonstrates that the novel factor Xa inhibitor apixaban is better than aspirin for the prevention of stroke in AF patients who are unable to take warfarin. Stuart Connolly and investigators in the AVERROES (Apixaban Versus Acetylsalicylic Acid [ASA] to Prevent Strokes) trial randomized 5599 AF patients who were deemed by their physicians to be unsuitable for vitamin K antagonist therapy to either apixaban (5 mg twice daily) or aspirin (81-324 mg per day). Results of the trial were first presented last year at the ESC.

AVERROES was stopped early by the data and safety monitoring committee after they observed “a clear benefit in favor of apixaban.” Stroke or systemic embolism, the primary outcome of the trial, occurred in 51 patients receiving apixaban compared to 113 receiving aspirin. Here are the rates per year and hazard ratios of the important endpoints:

  • Primary outcome: 1.6% per year in the apixaban group versus 3.7% in the aspirin group (HR 0.45; 95% CI 0.32-0.62, p<0.001)
  • Death: 3.5% per year versus 4.4% (HR 0.79, 95% CI 0.62-1.02, p=0.07)
  • Major bleeding: 1.4% per year versus 1.2% (HR 1.13, 95% CI 0.74-1.75, p=0.57)
  • First hospitalization for cardiovascular cause: 12.6% per year versus 15.9% (p<0.001)

The authors calculated that treating 1000 patients for 1 year with apixaban instead of aspirin would prevent 21 strokes or systemic emboli, 9 deaths, and 33 hospitalizations for cardiovascular causes, but would cause 2 additional major bleeds.

The AVERROES investigators pointed out that warfarin is not taken by one-third of patients who are considered “ideal candidates” for the drug: “The reluctance of patients to use a vitamin K antagonist is not surprising, given the inconvenience of INR monitoring, the lifestyle changes required, and the real and perceived difficulties associated with warfarin therapy.”

A separate trial, ARISTOTLE, a direct comparison of warfarin and apixaban in AF, is scheduled to be completed in April of this year.

Categories: Anticoagulation, Electrophysiology
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3 Responses to “Apixaban Better Than Aspirin for Stroke Prevention in AF Patients Unable to Take Warfarin”

  1. John Mandrola, MD, FACC says:
    February 10, 2011 at 6:02 pm

    Nice summary, Larry.

    I have a couple of thoughts on this trial.

    First the obvious: if we assume apixaban thins the blood equivalently to warfarin then these results are not very surprising. In AF stroke prevention surpassing ASA is indeed a low bar.

    Second, it’s telling that a cohort of patients called “non-suitable” for warfarin didn’t have an increase in bleeding. Obviously these patients were not unsuitable because of an increased bleeding risk.

    In my world, patients unsuitable for warfarin are those with a high bleeding risk, not those who didn’t want the drug (who does), or those with bouncy INRs (which in most cases can be stabilized with dietary instructions).

    All that said, apixaban looks good, as does rivaroxaban. I look forward to the upcoming bans vs trans (dabigatran) match.

    Competing interests pertaining specifically to this post, comment, or both:
    None

  2. William DeMedio, MD says:
    February 10, 2011 at 10:21 pm

    OK, so it “works better” than ASA at stroke prevention. How much so? Absolute risk reduction for death crosses 1.0 on the 95% C.I. (not significant). Does it prevent cancer? How does it fare regarding hemorrhagic stroke and major bleeding elsewhere? How do you do the fuzzy math and come up with 9 less deaths per thousand treated when the risk reduction for death is not stastically significant compared to ASA? How much more does it cost than ASA? I hope Aristotle answers some of these questions.

    Competing interests pertaining specifically to this post, comment, or both:
    None.

  3. Stephen Austin, MD says:
    February 11, 2011 at 12:13 pm

    Clearly, the more important study results will be those of the ARISTOTLE study in which apixaban is being directly compared to warfarin, as the current standard of care, in terms of either non-inferiority or superiority. If the two therapies are comparable, then cost differential becomes a real world consideration.

    Competing interests pertaining specifically to this post, comment, or both:
    None