Debra L. BeckEugene Braunwald, MD
Date Published: 11 Sep 2019
Approximately 15% of patients with atrial fibrillation (AF) require percutaneous coronary intervention (PCI) at some point to treat obstructive coronary artery disease (CAD). Current guidelines recommend oral anticoagulation for AF and dual antiplatelet therapy with aspirin and a P2Y12 inhibitor after PCI. However, this triple therapy strategy is associated with high bleeding risk. Edoxaban is approved for stroke prevention in AF. Goette et al sought to assess the safety of edoxaban plus a P2Y12 inhibitor compared to a vitamin-K antagonist (VKA) plus a P2Y12 inhibitor plus aspirin in patients with AF after PCI.
ENTRUST-AF PCI was a phase 3b, randomized, open-label, noninferiority trial that included 1506 patients with AF requiring oral anticoagulation who had a successful PCI for stable CAD or acute coronary syndrome. Participants were randomly assigned from 4 hours to 5 days post-PCI to either edoxaban 60 mg once daily plus a P2Y12 inhibitor or VKA plus a P2Y12 inhibitor and aspirin. In patients with reduced renal function, low bodyweight, or concomitant use of a potent P-glycoprotein inhibitor, edoxaban dosing was reduced to 30 mg daily. The trial was conducted at 186 sites in 18 countries.
About 92% of participants were taking clopidogrel, and the remainder prasugrel or ticagrelor.
For the primary endpoint, a composite of International Society of Thrombosis and Haemostasis-defined major bleeding or clinically-relevant non-major bleeding within 12 months, edoxaban was noninferior to triple therapy, with annualized event rates of 20.7% and 25.6%, respectively (hazard ratio, 0.83; p=0.001 for noninferiority and p=0.1154 for superiority). Bleeding outcomes using other definitions of bleeding (TIMI and BARC) were the same.
For the main efficacy outcome, a composite of cardiovascular death, stroke, systemic embolic event, myocardial infarction, or definite stent thrombosis, the two strategies were similar: annualized event rates were 7.3% for the edoxaban regimen and 6.9% for the VKA-based regimen (HR, 1.06; p=NS).
In patients with AF who underwent PCI, an edoxaban-based regimen was noninferior to a VKA-based regimen in terms of major and clinically-relevant nonmajor bleeding, without significant differences in ischemic events.
The investigators noted some limitations of their study, including the open-label design and that the sample size was not large enough to detect “small but potentially important differences in the incidence of the main efficacy outcome.”
In his scheduled comments on the trial, Dr. R Lopes noted that this trial was small as compared to other similar trials (PIONEER, RE-DUAL PCI, AUGUSTUS), but adds to the body of evidence in a field where high-quality evidence is needed. “In 2019, with about 12,000 patients from randomized trials, I think we can say that for most patients with a-fib undergoing PCI, after the initial few days from PCI, using a NOAC plus a P2Y12 inhibitor without aspirin should be the preferred regimen and VKA plus a P2Y12 inhibitor plus aspirin should generally be avoided,” Dr. Lopes concluded.
Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine features a unique update program by Dr. Braunwald, creating a “living textbook” by featuring weekly Hot off the Press, periodic Late-Breaking Clinical Trials (including links to authors’ presentation slides), and monthly Focused Reviews.
Learn more about Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine, 11th Edition. Download a free chapter here.