NOAC with P2Y12i as good as VKA, P2Y12i and aspirin for bleeding outcomes in AF patients after PCI

Edoxaban-vs vitamin-K-antagonist-based anti-thrombotic regimen after successful coronary stenting in patients with atrial fibrillation (ENTRUST-AF PCI): A randomised, open-label, phase 3b trial

Presented at the ESC congress 2019 in Paris, France by: Andreas Goette (Paderborn, Germany)

Introduction and methods

Approximately 15% of AF patients require PCI with stent placement for treatment of obstructive coronary artery disease (CAD). After PCI, oral anticoagulant with dual antiplatelet therapy (DAPT), consisting of aspirin with a P2Y12 inhibitor, is recommended by guidelines. However, this triple therapy is associated with increased risk of bleeding.

Previous randomized trials have examined the effects of NOACs in AF patients undergoing PCI without use of aspirin. Effects of edoxaban in combination with a P2Y12 inhibitor in AF patients undergoing PCI have not been studied yet.

Therefore, 12-months regimen of edoxaban plus a P2Y12 inhibitor was compared to VKA plus a P2Y12 inhibitor plus 1-12 months of aspirin in AF patients with ACS or stable CAD following successful PCI with regard to incidence of major or clinically relevant non-major bleeding (defined by ISTH criteria).

The TRUST-AF PCI was a prospective, randomized, open label, blinded endpoint evaluation trial enrolling 1506 AF patients with ACS or stable CAD in 186 centers in 18 countries. Patients were randomized to the edoxaban regimen or VKA regimen.

Main results

• Annualized event rate of the primary study endpoint (major or clinically relevant non-major bleeding) was 20.7% in the edoxaban regimen group and 25.6% in the VKA regimen (HR: 0.83, 95%CI: 0.65-1.05, Pnon-inferiority=0.0010, superiority=0.1154).
• Annualized event rate of the main efficacy endpoint, a composite of CV death, stroke, SEE, MI or definite stent thrombosis, was 7.3% in the edoxaban regimen group and 6.9% in the VKA regimen (HR: 1.06, 95%CI:0.71-1.69).
• Other bleeding outcomes were not different between regimens.
• Post-hoc landmark Kaplan Meier analysis of the primary study endpoint showed an increased risk with edoxaban when compared to VKA regimen during the first phase of the trial (≤14 days) (HR: 2.42, 95%CI:1.27-4.63) and reduced risk with edoxaban in comparison to VKA regimen in the later phase (>14 days) (HR:0.68, 95%CI:0.53-0.88) (Pinteraction<0.0001). Percentage of patients with INR <2 in the VKA regiment group was 94% at day 1, 69% from day 2-7 and 42% from day 8-14, which might explain the difference in findings between the two phases of the trial.

Result of meta-analysis

• A meta-analysis of four trials (AUGUSTUS, ENTRUST-AF PCI, PIONEER-AF PCI, RE-DUAL PCI) with ISTH major or clinically relevant non-major bleeding as outcome showed a benefit with NOAC dual therapy when compared to VKA triple therapy (HR: 0.62, 95%CI:0.47-0.81, test for overall effect Z=3.47, P=0.0005).
• Outcomes of myocardial infarction and stent-thrombosis were not different between the two regimen (HR:1.18, 95%CI:0.93-1.52; and HR:1.55, 95%CI:0.99-2.41, respectively).

Conclusion

In AF patients who underwent PCI, regimen of edoxaban plus a P2Y12 inhibitor was non-inferior to triple therapy consisting of VKA, P2Y12 inhibitor and 1-12 months aspirin with regard to major or non-clinically relevant bleedings at 12 months. Main efficacy outcome, a composite of ischemic events, was not different between the edoxaban and VKA regimens.

- Our reporting is based on the information provided at the ESC congress -

This study was simultaneously published in The Lancet