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

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

AUGUSTUS is an international, multicentre, randomised trial with a 2x2 factorial design to compare apixaban + aspirin or placebo with a VKA + aspirin or 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 oral anticoagulation and a P2Y12 inhibitor for all patients.

Primary outcome of the study was the composite of major or clinically relevant non-major (CRNM) 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, 6 hours), and ACS or PCI, and planned on receiving a P2Y12 inhibitor for 6 months. Exclusion criteria were contraindication to dual antiplatelet therapy and other reasons for VKA, such as prosthetic valve or mitral stenosis. Patients (n=4,614) were randomised to either apixaban 5 mg BID (2.5 mg in selected patients) + aspirin or placebo, and VKA (INR 2-3) + aspirin or placebo.

In general, the stent thrombosis rate in the study as a whole was less than 1%. The percentage of definite or probable stent thrombosis in patients treated with apixaban (n=2,306) was 0.6% vs 0.8% in those on VKA (n=2,308; HR 0.77; 95% CI, 0.38-1.56). For those on aspirin (n=2,307), definite or probable stent thrombosis occurred in 0.5% vs 0.9% in those on placebo (n=2,307; HR 0.52; 95% CI, 0.25-1.08). However, this trial was not powered for ischaemic risk.

Results also showed that the cumulative incidence of events for major/CRNM 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 the aspirin groups and 9% for the placebo groups (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).

For the secondary outcome, 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. Abstract 407-13. ACC 2019, 16-18 March, New Orleans, USA.



Posted on 4 June, 20198 February, 2024