Highlights from

ACC 2019

American College of Cardiology Annual Scientific Session & Expo

New Orleans 16-18 March 2019

Less bleeding and fewer hospitalisations with antithrombotic regimen with apixaban but without aspirin

Results from the AUGUSTUS trial show that atrial fibrillation (AF) patients with recent acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI) who receive a P2Y12 inhibitor, an antithrombotic regimen that includes apixaban, without aspirin, have less bleeding and fewer hospitalisations without significant differences in ischaemic events than regimens that include a vitamin K antagonist (VKA), aspirin, or both [1].

The optimal antithrombotic strategy for patients with AF who develop an ACS and/or undergo PCI is uncertain. The risk of bleeding increases when oral anticoagulation (OAC) given to reduce stroke risk associated with AF is combined with antiplatelet therapy, which is administered to reduce the risk of recurrent coronary ischaemic events.

Study design and outcomes

AUGUSTUS is an international, multicentre, randomised trial with a 2 x 2 factorial design to compare apixaban with a VKA, and aspirin with placebo in patients with AF who develop ACS and/or undergo PCI and are receiving a P2Y12 inhibitor. As such, it is the largest and only prospective randomised trial to investigate efficacy and safety of aspirin vs placebo with either non-VKA or VKA OAC and a P2Y12 inhibitor for all patients.

Primary outcome of the study was the composite of major or clinically relevant non-major (CNRM) bleeding defined by the International Society on Thrombosis and Haemostasis (ISTH). Key secondary outcomes included the composite of death or hospitalisation, and recurrent ischaemic events (i.e. death, myocardial infarction, stroke, stent thrombosis, or urgent revascularisation).

Eligible patients had AF (prior, persistent, >6hr), and ACS or PCI (planned P2Y12 inhibitor for ≥6 months). Exclusion criteria were contraindication to DAPT and other reason for VKA, such as prosthetic valve, moderate severe mitral stenosis. A total of 4,600 AF patients were randomised to either apixaban 5 mg BID (2.5 mg in selected patients) + aspirin or placebo and VKA (INR 2-3) + placebo, or placebo.

Major/CNRM bleeding outcomes

Results show that the cumulative incidence of events for major/CNRM bleeding was 10.5% for apixaban and 14.7% for VKA (HR 0.69 [95% CI 0.58-0.81, P<0.001]); this was 16.1% for aspirin and 9% for placebo (HR 1.89 [95% CI 1.59-2.24, P<0.001]). For VKA + aspirin this was 18.7%, for apixaban + aspirin 13.8%, for VKA + placebo 10.9%, and for apixaban + placebo 7.3%. The absolute risk reduction with apixaban + placebo vs VKA + aspirin was 11.4% (number needed to treat 9).

Death/hospitalisation outcomes

The cumulative incidence of events for death/hospitalisation was 23.5% for apixaban and 27.4% for VKA (HR 0.83 [95% CI 0.74-0.93, P=0.002]); this was 26.2% for aspirin and 24.7% for placebo (HR 1.08 [95% CI 0.96-1.21, P=0.20]). For VKA + aspirin, this was 25.7%, for apixaban + aspirin 24.9%, for VKA + placebo 27.3%, and for apixaban + placebo 22.0%. The absolute risk reduction with apixaban + placebo vs VKA + aspirin was 5.5% (number needed to treat 18).

  1. Lopes RD, et al. An Open-label, 2 x 2 Factorial, Randomized Trial to Evaluate the Safety of Apixaban versus Vitamin K Antagonist and Aspirin versus Placebo in Patients with Atrial Fibrillation and Acute Coronary Syndrome and/or Percutaneous Coronary Intervention: Primary Results of the AUGUSTUS Trial. Abstract 407-13. ACC2019, 16-18 March, New Orleans, USA.

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