Relative Benefit of Dual Versus Single Antiplatelet Therapy Among Patients With Atrial Fibrillation on Oral Anticoagulation According to Time After ACS and PCI: Insights From the AUGUSTUS Trial.

Background: In the AUGUSTUS trial (An Open-Label, 2 x 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 or Percutaneous Coronary Intervention), the combination of dual antiplatelet therapy plus oral anticoagulation increased the risk of bleeding without reducing ischemic events compared with a P2Y12 inhibitor plus oral anticoagulation among patients with atrial fibrillation and acute coronary syndrome or elective percutaneous coronary intervention. However, AUGUSTUS enrolled patients up to 14 days after acute coronary syndrome or percutaneous coronary intervention, and there may be a benefit to dual antiplatelet therapy plus oral anticoagulation early after an ischemic event.

Methods: In this secondary analysis of AUGUSTUS, we divided patients into groups based on whether they were enrolled <6 days (early) or ≥6 days (later) after their index acute coronary syndrome or percutaneous coronary intervention, and tested the interaction between time from the index event to enrollment and randomized treatment (apixaban versus vitamin K antagonist and aspirin versus placebo) on 30-day and 6-month clinical outcomes using Cox proportional hazards models.

Results: Among 4605 patients enrolled in AUGUSTUS with data available on time from the index event to enrollment, the median time from the index event to enrollment was 6 (range, 0-14) days. There were no significant interactions between time from the index event and aspirin versus placebo on clinical outcomes at 30 days or 6 months, though patients with time from the index event <6 days had a nominally significant reduction in death or ischemic events at 30 days with aspirin (hazard ratio, 0.55 [95% CI, 0.30-0.99]), whereas patients with time from the index event ≥6 days did not (hazard ratio, 0.88 [95% CI, 0.54-1.43]; interaction P=0.23). There were no significant interactions between time from the index event and apixaban versus vitamin K antagonist on clinical outcomes.

Conclusions: Among patients with atrial fibrillation with acute coronary syndrome or undergoing percutaneous coronary intervention, there was no difference in the relative benefit of apixaban versus vitamin K antagonist or aspirin versus placebo when patients were enrolled early versus later after their index event.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02415400.