Edoxaban Monotherapy Triumphs in AF and Stable Coronary Disease: Insights from EPIC-CAD

The EPIC-CAD trial has provided compelling evidence that for patients with high-risk atrial fibrillation (AF) and stable coronary artery disease (CAD), the optimal treatment strategy involves the use of anticoagulation monotherapy, specifically Edoxaban, rather than a combination therapy that includes antiplatelet agents. This groundbreaking study, presented at the European Society of Cardiology Congress 2024, highlighted a significant reduction in net adverse clinical events (NACE) after one year for patients treated solely with Edoxaban compared to those receiving both Edoxaban and an antiplatelet agent. The findings were primarily driven by a marked decrease in bleeding events, while the risks of ischemic events and mortality remained comparable between the two groups.

Dr. Gi-Byoung Nam, co-principal investigator of the EPIC-CAD trial, emphasized the importance of these results, noting that they address a critical challenge in managing patients with both AF and CAD. These patients often face increased bleeding risks when subjected to dual therapy involving oral anticoagulation and antiplatelet agents. Current guidelines recommend such dual therapy for the first 6-12 months following percutaneous coronary intervention (PCI) or acute coronary syndrome (ACS) in patients who require oral anticoagulation. However, the evidence supporting the continuation of anticoagulation monotherapy beyond this initial period has been limited until now.

The EPIC-CAD trial included 1,038 patients with high-risk AF and stable coronary disease, who were randomized to receive either Edoxaban monotherapy or Edoxaban in combination with aspirin or a P2Y12 inhibitor. The primary endpoint of the study was a composite measure that included all-cause death, stroke, systemic embolism, myocardial infarction (MI), unplanned urgent revascularization, major bleeding, and clinically relevant non-major bleeding. After one year, the results demonstrated a clear advantage for Edoxaban monotherapy, with a number needed to treat of just 10.6 to prevent one adverse event.

Dr. Duk-Woo Park, another co-principal investigator, stated that the trial’s findings strongly support the safety and efficacy of providing oral anticoagulation alone in patients with chronic coronary disease and AF. The study showed no significant differences between the two groups in terms of individual efficacy endpoints such as death and ischemic events. However, there was a notable reduction in various bleeding endpoints among patients receiving Edoxaban monotherapy, underscoring the benefits of this approach in minimizing bleeding risks without compromising efficacy.

The EPIC-CAD trial is not an isolated study in this field. Dr. Marco Valgimigli pointed out that it is the fifth trial to explore the use of concomitant antiplatelet therapy with oral anticoagulation in patients with AF and coronary disease. Previous trials, including OAC-ALONE, AFIRE, PRAE-DO AF, and MASTER-DAPT, have consistently shown that dual therapy with antiplatelet agents is not necessary and leads to increased bleeding risk. These studies collectively reinforce the guideline recommendation to switch to anticoagulation monotherapy after the initial 6-12 month period following PCI or ACS.

In addition to the EPIC-CAD trial, ongoing studies are further comparing direct oral anticoagulant (DOAC) monotherapy with dual antithrombotic therapy in patients with an indication for oral anticoagulation. These efforts aim to provide even more robust evidence to guide clinical practice and ensure that patients receive the most effective and safest treatment regimens. The hope is that the medical community will increasingly adopt these evidence-based guidelines, thereby improving patient outcomes and reducing the risks associated with unnecessary dual therapy.

The study, which was also published in the New England Journal of Medicine, involved an open-label, randomized design with 1,040 patients who had a CHA2DS2-VASc score of ≥2 and stable CAD. Patients were randomly assigned to receive either Edoxaban monotherapy or dual therapy with Edoxaban and an antiplatelet agent. The primary endpoint was a composite of various adverse events at one year after randomization, with key secondary endpoints including major ischemic events and major or clinically relevant non-major bleeding.

Among the study participants, two-thirds had undergone previous revascularization, and the mean age was 72 years, with 23% being women. The mean CHA2DS2-VASc score was 4.3, indicating a high risk of stroke, while the mean HAS-BLED score, reflecting bleeding risk, was 2.1. In the dual therapy group, more patients received aspirin (62%) than clopidogrel (38%). The results showed that Edoxaban monotherapy reduced the risk of the primary endpoint by 56% compared to dual therapy, mainly due to a 66% reduction in bleeding events. There was no difference in the rate of major ischemic events or all-cause mortality between the two groups.

These findings align with previous research, such as a trial that found rivaroxaban monotherapy to be non-inferior to dual therapy in similar patient populations. The consistency of these results across multiple studies adds weight to the argument for using anticoagulation monotherapy in patients with AF and stable CAD. By minimizing bleeding risks without increasing the incidence of major ischemic events, Edoxaban monotherapy offers a safer and equally effective alternative to the traditional dual therapy approach.

The implications of the EPIC-CAD trial are significant for clinical practice. For cardiologists and other healthcare providers managing patients with AF and stable CAD, these findings provide a clear rationale for favoring anticoagulation monotherapy over dual therapy. This shift in treatment strategy can lead to better patient outcomes, reduced hospitalizations due to bleeding complications, and overall improved quality of life for patients. Moreover, the study underscores the importance of personalized medicine, where treatment decisions are tailored to the individual patient’s risk profile and clinical history.

As the medical community continues to digest and implement the findings from the EPIC-CAD trial and other related studies, it is crucial to maintain a focus on patient education and shared decision-making. Patients should be informed about the potential benefits and risks associated with different treatment options, empowering them to participate actively in their care. This collaborative approach can enhance adherence to prescribed therapies and ultimately contribute to better health outcomes.

In conclusion, the EPIC-CAD trial represents a pivotal advancement in the management of patients with high-risk AF and stable CAD. By demonstrating the superiority of Edoxaban monotherapy over dual therapy with antiplatelet agents, the study provides a robust evidence base for optimizing antithrombotic treatment in this patient population. As ongoing research continues to refine our understanding of the best therapeutic strategies, the insights gained from the EPIC-CAD trial will undoubtedly play a critical role in shaping future guidelines and improving patient care.