Background: In AUGUSTUS (Open-Label, 2×2 Factorial, Randomized, Controlled Clinical Trial to Evaluate the Safety of Apixaban vs Vitamin K Antagonist and Aspirin vs Aspirin Placebo in Patients With Atrial Fibrillation and Acute Coronary Syndrome and/or Percutaneous Coronary Intervention), patients with atrial fibrillation and a recent acute coronary syndrome and those undergoing percutaneous coronary intervention had less bleeding with apixaban than vitamin K antagonist (VKA) and with placebo than aspirin. However, the number of ischemic events was numerically higher with placebo. The aim of this analysis is to assess the tradeoff of risk (bleeding) and benefit (ischemic events) over time with apixaban versus VKA and aspirin versus placebo.
Methods: In AUGUSTUS, 4614 patients with atrial fibrillation and recent acute coronary syndrome or percutaneous coronary intervention on a P2Y12 inhibitor were randomized to blinded aspirin or placebo and to open-label apixaban or VKA for 6 months. In a post hoc analysis, we compared the risk of 3 composite bleeding outcomes and 3 composite ischemic outcomes from randomization through 30 days and from 30 days to 6 months with apixaban and VKA and with aspirin and placebo.
Results: Compared with VKA, apixaban had either a lower or a similar risk of bleeding and ischemic outcomes from randomization to 30 days and from 30 days to 6 months. From randomization to 30 days, aspirin caused more severe bleeding (absolute risk difference, 0.97% [95% CI, 0.23-1.70]) and fewer severe ischemic events (absolute risk difference, -0.91% [95% CI, -1.74 to -0.08]) than placebo. From 30 days to 6 months, the risk of severe bleeding was higher with aspirin than placebo (absolute risk difference, 1.25% [95% CI, 0.23-2.27]), whereas the risk of severe ischemic events was similar (absolute risk difference, -0.17% [95% CI, -1.33 to 0.98]).
Conclusions: In patients with atrial fibrillation and recent acute coronary syndrome or percutaneous coronary intervention receiving a P2Y12 inhibitor, apixaban is preferred over VKA. Use of aspirin immediately and for up to 30 days results in an equal tradeoff between an increase in severe bleeding and a reduction in severe ischemic events. After 30 days, aspirin continues to increase bleeding without significantly reducing ischemic events. These results inform shared, patient-centric decision making on the ideal duration of the use of aspirin after an acute coronary syndrome or percutaneous coronary intervention in patients with atrial fibrillation receiving oral anticoagulation. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02415400.
Keywords: anticoagulants; apixaban; aspirin; hemorrhage; thrombosis; warfarin.