Improved outcomes with DOAC in AF and ACS and/or PCI independent of bleeding and stroke risk
Antithrombotic Therapy in Patients With Atrial Fibrillation After Acute Coronary Syndromes or Percutaneous Intervention
Introduction and methods
Patients with AF and who have an acute coronary syndrome (ACS) and/or undergo percutaneous coronary intervention (PCI) have an indication for both anticoagulation and dual antiplatelet therapy (DAPT) [1,2]. Triple antithrombotic therapy, however, is associated with a very high risk of bleeding complications .
The AUGUSTUS trial demonstrated that double antithrombotic therapy with a P2Y12 inhibitor in combination with a DOAC reduced ischemic outcomes while avoiding major bleeding in many of these patients . However, there may be subgroups that benefit from more potent antithrombotic regimen .
The AUGUSTUS trial was a multicenter, 2-by-2 factorial, RCT comparing apixaban with VKA and aspirin with placebo. Eligible patients had AF requiring OAC therapy and were hospitalized for ACS and/or underwent PCI with planned use of a P2Y12 inhibitor.
A non-prespecified post hoc analysis of the AUGUSTUS trial was performed to assess safety and efficacy of antithrombotic regimens according to the bleeding score HAS-BLED  and the stroke score CHA2DS-VASc  in 4386 patients with AF and ACS and/or PCI.
HAS-BLED and CHA2DS-VASc score ≤2 was defined as low risk and scores ≥3 was defined as high risk.
Safety outcomes were occurrence of major bleeding and major or clinically relevant nonmajor (CRNM) bleeding defined by the ISTH through 6 months of follow-up. Efficacy outcomes included stroke; a composite of death or ischemic events including stroke, MI, probable or definite stent thrombosis, or urgent revascularization; and death or any hospitalization.
- Patients in the apixaban group had lower rates of ISTH major or CRNM bleeding compared to those assigned to VKA, irrespective of HAS-BLED score (HR 0.57, 95%CI:0.41-0.78 for HAS-BLED ≤2; HR 0.72, 95%CI: 0.59-0.88 for HAS-BLED ≥3, Pinteraction=0.23)
- Similar results were observed for ISTH major bleeding.
- Patients in the aspirin group had higher rates of major or CRNM bleeding compared with those assigned to placebo, irrespective of HAS-BLED score (HR 1.86, 95%CI:- 1.36-2.58 for HAS-BLED ≤2; HR 1.81, 95%CI: 1.47-2.23 for HAS-BLED ≥3, Pinteraction=0.88).
- Results were similar for ISHT major bleeding.
- No strokes occurred in patients with CHA2DS-VASc score ≤2. Therefore, no interaction testing could be done.
- There were no difference in treatment effect for apixaban vs VKA or aspirin vs. placebo for the composite of death or ischemic events or the composite of death or hospitalization when stratified by CHA2DS-VASc score.
- When looking at death or hospitalization, apixaban resulted in a lower risk than VKA without a significant interaction with baseline CHA2DS-VASc score (HR: 0.92; 95% CI: 0.67-1.25 for CHA2DS2-VASc≤2 and HR: 0.82; 95% CI: 0.73-0.94 for CHA2DS2-VASc≥3, Pinteraction=0.53).
In this post hoc analysis of the AUGUSTUS trial changes in bleeding outcomes, rates of death or hospitalization and ischemic events in those randomized to apixaban vs. VKA were independent of baseline bleeding or stroke risk.
The authors conclude that the treatment regimen in the AUGUSTUS trial consisting of apixaban and a P2Y12 inhibitor without aspirin is preferred across a wide range of bleeding and stroke scores in patients with AF and ACS and/or PCI.