Introduction

In atrial fibrillation patients with an acute coronary syndrome (ACS) or have undergone percutaneous coronary intervention (PCI), there is a need for an oral antithrombotic regimen with an acceptable benefit–risk profile, however, there is unclear data. Regimens including non–vitamin K antagonist oral anticoagulants may have an edge over vitamin K antagonists, including the potential for less bleeding.

Aim

To assess the safety and efficacy of standard-dose apixaban in comparison with a vitamin K antagonist and of low-dose aspirin in comparison with placebo, in atrial fibrillation patients with recent ACS or PCI and receiving concomitant P2Y₁₂ inhibitor therapy for 6 months

Patient Profile

4614 patients with atrial fibrillation who had a recent ACS or underwent PCI (or both) and on an oral anticoagulant and a P2Y12 inhibitor for at least 6 months

Method-

Study Design

• AUGUSTUS trial was a 6-month, prospective, multicenter, two-by two factorial, randomized, controlled clinical trial comparing apixaban (5 mg or 2.5 mg twice daily) with a vitamin K antagonist (dose adjusted for a target international normalized ratio of 2.0 - 3.0) in an open-label design
• The second part of the trial comparing antiplatelet-regimen, aspirin (81 mg once daily), with placebo in a double-blind design

  Endpoints

• Primary safety outcome: major or clinically relevant nonmajor bleeding
• Secondary efficacy outcomes: death or hospitalization and a composite of ischemic events (stroke, myocardial infarction, stent thrombosis, or urgent revascularization)

Results

• Apixaban was associated with significantly lower major or clinically relevant nonmajor bleeding in the atrial fibrillation patients as compared to those receiving a vitamin K antagonist (10.5% vs. 14.7%, hazard ratio, 0.69; P<0.001; Figure 1)
• The number needed to treat over a period of 6 months to avoid one International Society on Thrombosis and Haemostasis (ISTH) major or clinically relevant nonmajor bleeding event with apixaban instead of a vitamin K antagonist was 24
• The major or clinically relevant nonmajor bleeding event rate was significantly higher among those receiving aspirin than among those receiving placebo (16.1% vs. 9.0%, hazard ratio 1.89; P<0.001).
• The number needed to harm over a period of 6 months to cause one ISTH major or clinically relevant nonmajor bleeding event with aspirin instead of placebo was 14
• Apixaban and placebo were associated with lesser primary bleeding outcome events vs. those receiving a vitamin K antagonist and aspirin (7.3% vs. 18.7% patients)
• Apixaban significantly lowered the incidence of death or hospitalization as compared to vitamin K antagonist (23.5% vs. 27.4%; hazard ratio, 0.83; P = 0.002)
• The number needed to treat over a period of 6 months to avoid one death or hospitalization with apixaban instead of a vitamin K antagonist was 26
• Aspirin reduced the incidence of death or hospitalization similar to that of placebo (26.2% vs. 24.7%; hazard ratio 1.08)
• At 6 months, 6.7% who had been assigned to receive apixaban had died or had had an ischemic event — including myocardial infarction, definite or probable stent thrombosis, stroke, or urgent revascularization as compared with 7.1% who had been assigned to receive a vitamin K antagonist.
• No difference was observed in ischemic events (myocardial infarction, stent thrombosis, stroke, or urgent revascularization) between apixaban versus vitamin K antagonist (6.7% vs. 7.1%) or aspirin versus placebo (6.5% vs. 7.3% patients)

Figure 1: Effect of apixaban in comparison with vitamin K antagonist on primary safety outcome

Conclusion

In patients with atrial fibrillation and a recent acute coronary syndrome or PCI treated with a P2Y12 inhibitor, an antithrombotic regimen that included apixaban, without aspirin, resulted in less bleeding and fewer hospitalizations without significant differences in the incidence of ischemic events than regimens that included a vitamin K antagonist, aspirin, or both.

N Engl J Med 2019; 380: 1509-24