EPIC-CAD: What is the best antithrombotic approach in high-risk AF plus stable CAD?

Edoxaban monotherapy was associated with lower bleeding than edoxaban plus antiplatelet therapy in patients with high-risk atrial fibrillation (AF) and stable coronary artery disease (CAD) in the large EPIC-CAD trial. Ischaemic event rates were low and the risk for bleeding was significantly reduced in the monotherapy arm.

“Choosing the optimal antithrombotic therapy for patients with CAD and AF is challenging,” expressed Dr Gi-Byoung Nam (Ulsan University Hospital, South Korea) [1]. “Patients with AF need prevention of thromboembolic events with anticoagulants and patients with CAD need antiplatelet therapy to prevent ischaemic events.” The combined use of these drugs comes with an increased risk of bleeding [2]. The authors of the current study hypothesised that edoxaban monotherapy would be superior to dual antithrombotic therapy in terms of a combined ischaemic and bleeding endpoint in patients with CAD and AF [1,3].

In the phase 4 EPIC-CAD trial (NCT03718559), 1,038 participants with high-risk AF and stable CAD from 18 sites in South Korea were randomised 1:1 to edoxaban monotherapy or to dual antithrombotic therapy with edoxaban plus a single anti-platelet agent. Stable CAD was defined as revascularisation for a chronic coronary syndrome at least 6 months prior, revascularisation for ACS at least 12 months prior, or anatomically confirmed coronary disease managed without revascularisation. The primary endpoint was a composite of all-cause death, stroke, systemic embolic events, myocardial infarction, unplanned urgent revascularisation, major bleeding, and clinically relevant non-major bleeding after 1 year of therapy.

Dual antithrombotic therapy led to more adverse events than edoxaban monotherapy, as revealed by the primary outcome (16.2% vs 6.8%; HR 0.44; 95% CI 0.30–0.65; P<0.001). The incidence of major ischaemic events was low in both of the 2 study arms (1.8% vs 1.6%; HR 1.23; 95% CI 0.48–3.10), whereas major or clinically relevant non-major bleeding was more common in the dual antithrombotic therapy arm than in the monotherapy arm (14.2% vs 4.7%; HR 0.34; 95% CI 0.22−0.53). Dr Nam acknowledged that the trial was underpowered for ischaemic thrombotic events as a sole endpoint.

The EPIC-CAD study suggests that edoxaban monotherapy is linked to a lower risk of bleeding compared with dual antithrombotic therapy with edoxaban and an antiplatelet agent in patients with AF and stable CAD. “The effect appeared to be driven by a decreased risk for bleeding events in the monotherapy arm,” concluded Dr Nam.

1. 
   
   1. Nam G-B, et al. Edoxaban-based long-term antithrombotic therapy for atrial fibrillation and stable coronary disease: The EPIC-CAD randomised clinical trial. HOTLINE 6, ESC Congress 2024, 30 Aug–02 Sept, London, UK.
   2. Gibson CM, et al. N Engl J Med 2016;375:2423.
   3. Cho MS, et al. N Engl J Med 2024; 1 Sept. DOI: 10.1056/NEJMoa2407362.

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Posted on 7 November 20247 November 2024