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

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

Exclusion criteria:

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

Other salient features/characteristics:

  • 52% with acute coronary syndrome
  • 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).

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. 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-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;Sep 3:[Epub ahead of print].

Editorial Comment: Capodanno D, Angiolillo DJ. Dual antithrombotic therapy for atrial fibrillation and PCI. Lancet 2019;Sep 3:[Epub ahead of print].

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, 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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