Edoxaban-Based Antithrombotic Regimen in Patients With Atrial Fibrillation - ENTRUST-AF PCI

Aug 31, 2020
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Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Daiichi Sankyo
Date Presented:
08/28/2020
Date Published:
08/29/2020
Date Updated:
08/31/2020
Original Posted Date:
09/03/2019
References

Contribution To Literature:

The ENTRUST-AF PCI trial showed that edoxaban/clopidogrel was noninferior to vitamin K antagonist-based triple therapy.

Description:

The goal of the trial was to evaluate edoxaban/clopidogrel compared with vitamin K antagonist/dual antiplatelet therapy among patients with atrial fibrillation who recently underwent percutaneous coronary intervention (PCI).

Study Design

  • Randomized
  • Parallel
  • Open-label
  • Blocked

Patients with atrial fibrillation and recent PCI were randomized to edoxaban 60 mg daily plus clopidogrel 75 mg daily for 12 months (n = 751) vs. a vitamin K antagonist and clopidogrel 75 mg daily for 12 months plus aspirin (100 mg once daily, for 1-12 months) (n = 755).

Edoxaban was reduced to 30 mg daily if the calculated creatinine clearance was 15-50 ml/min, weight <60 kg, or concurrent use of specific potent P-glycoprotein inhibitors.

  • Total number of enrollees: 1,506
  • Duration of follow-up: 12 months
  • Mean patient age: 69 years
  • Percentage female: 26%
  • Percentage with diabetes: 34%

Inclusion criteria:

  • Patients ≥18 years of age
  • Atrial fibrillation on anticoagulation
  • Previous PCI for stable coronary disease or acute coronary syndrome (ACS)

Exclusion criteria:

  • Mechanical heart valve
  • Moderate to severe mitral stenosis
  • End-stage renal disease
  • Other major comorbidities

Other salient features/characteristics:

  • 52% with ACS
  • 48% with stable coronary artery disease
  • In the vitamin K antagonist arm, the median time that aspirin was administered was 66 days.

Principal Findings:

The primary outcome, major or clinically relevant nonmajor bleeding at 12 months, occurred in 17% of the edoxaban group compared with 20% of the vitamin K antagonist group (p for noninferiority = 0.001, p for superiority = 0.12).

For secondary outcomes: Cardiovascular death, myocardial infarction, stroke, systemic embolism, or definite stent thrombosis was 7% with edoxaban vs. 6% with vitamin K antagonist (p = not significant).

Effect according to acute or chronic coronary artery disease: Among those with ACS, the primary outcome occurred in 15.2% of the edoxaban group vs. 20.3% of the vitamin K antagonist group. Among those with chronic coronary disease, the primary outcome occurred in 19.0% of the edoxaban group vs. 19.9% of the vitamin K antagonist group (p for interaction = 0.27).

Interpretation:

Among patients with atrial fibrillation and recent PCI, edoxaban/clopidogrel vs. vitamin K antagonist/dual antiplatelet therapy was noninferior for bleeding, with similar ischemic outcomes. The results were the same among those with either acute or chronic coronary disease. On this topic, this is the only trial with a novel oral anticoagulant that did not show superiority for bleeding compared with a vitamin K antagonist-based strategy.

The PIONEER AF-PCI (rivaroxaban), RE-DUAL PCI (dabigatran), and AUGUSTUS (apixaban) trials have all documented the safety of anticoagulation with a novel oral anticoagulant/mono-antiplatelet therapy (so-called “dual therapy”) in the first year after PCI.

In summary, several lines of evidence now support that a novel oral anticoagulant plus mono-antiplatelet therapy is safe for patients with atrial fibrillation and recent PCI.

References:

Vranckx P, Valgimigli M, Eckardt L, et al. Edoxaban in atrial fibrillation patients with percutaneous coronary intervention by acute or chronic coronary syndrome presentation: a pre-specified analysis of the ENTRUST-AF PCI trial. Eur Heart J 2020;Aug 29:[Epub ahead of print].

Presented by Dr. Pascal Vranckx at the European Society of Cardiology Virtual Congress, August 28, 2020.

Vranckx P, Valgimigli M, Eckardt L, et al. Edoxaban-based versus vitamin K antagonist-based antithrombotic regimen after successful coronary stenting in patients with atrial fibrillation (ENTRUST-AF PCI): a randomised, open-label, phase 3b trial. Lancet 2019;394:1335-43.

Editorial Comment: Capodanno D, Angiolillo DJ. Dual antithrombotic therapy for atrial fibrillation and PCI. Lancet 2019;394:1300-2.

Presented by Dr. Andreas Goette at the European Society of Cardiology Congress, Paris, France, September 3, 2019.

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Clinical Topics: Acute Coronary Syndromes, Anticoagulation Management, Arrhythmias and Clinical EP, Invasive Cardiovascular Angiography and Intervention, Atherosclerotic Disease (CAD/PAD), Anticoagulation Management and ACS, Anticoagulation Management and Atrial Fibrillation, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Interventions and ACS, Interventions and Coronary Artery Disease

Keywords: ESC Congress, ESC 19, ESC20, Acute Coronary Syndrome, Anticoagulants, Arrhythmias, Cardiac, Aspirin, Atrial Fibrillation, Coronary Artery Disease, Embolism, Hemorrhage, Myocardial Infarction, Myocardial Ischemia, Percutaneous Coronary Intervention, Stents, Stroke, Thrombosis, Vitamin K


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