Abstract
BACKGROUND: Studies have demonstrated the safety and efficacy of reducing the dose of apixaban from 5.0 mg to 2.5 mg twice daily in patients with atrial fibrillation (AF) and ≥2 dose-reduction criteria (age ≥80 years, body weight ≤60 kg, serum creatinine ≥1.5 mg/dL). However, data on reduced dose apixaban in patients with AF and acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI) are limited. OBJECTIVES: The authors aimed to assess clinical outcomes, including bleeding and death/ischemic events, according to apixaban dose in AUGUSTUS. METHODS: In AUGUSTUS, 4,614 patients with AF and/or recent ACS or PCI on a P2Y12 inhibitor were randomized to open-label apixaban or vitamin K antagonist (VKA) and blinded aspirin or placebo for 6 months. Apixaban dose was determined by investigators following the apixaban label. We assessed outcomes, including major/clinically relevant nonmajor bleeding and death/ischemic events, among patients who appropriately received reduced dose apixaban, inappropriately received reduced dose apixaban, and appropriately received standard dose apixaban compared with VKA. RESULTS: Of 2,290 patients assigned apixaban, 229 (10%) received reduced dose apixaban and 98 (43%) of those met dose-reduction criteria. Among patients receiving appropriately reduced, inappropriately reduced, and standard dose apixaban, rates of major/clinically relevant nonmajor bleeding were 13.7%, 10.5%, and 11.0%; rates of death or ischemic events were 12.2%, 12.3%, and 5.7%. When comparing the risk of clinical outcomes in the 3 groups (appropriately reduced, inappropriately reduced, and standard dose apixaban) vs matched patients receiving VKA, we found that patients receiving apixaban had more favorable outcomes than those receiving VKA, without significant interaction (P > 0.20 across all 3 groups and all outcomes). CONCLUSIONS: Of the ∼10% of patients in AUGUSTUS who received reduced dose apixaban, less than one-half met the dose-reduction criteria. In patients with AF and recent ACS or PCI, appropriately reduced dose apixaban was associated with a lower risk of bleeding and similar rates of ischemic outcomes compared with VKA, similar results were found with standard dose apixaban. (A Study of Apixaban in Patients With Atrial Fibrillation, Not Caused by a Heart Valve Problem, Who Are at Risk for Thrombosis [Blood Clots] Due to Having Had a Recent Coronary Event, Such as a Heart Attack or a Procedure to Open the Vessels of the Heart; NCT02415400).