2019, Volume 26, Supplement 2: Edoxaban – insights from pivotal studies and sub-analyses

Atrial fibrillation (AF) is the most common cardiac arrhythmia encountered in clinical practice, and its prevalence is increasing in both genders and across age groups.1 AF promotes increased risk of adverse clinical outcomes, including death, stroke, cardiovascular events and heart failure.2,3 Venous thromboembolism (VTE) is another common condition that predisposes to premature mortality, stroke and other adverse outcomes.4,5...

This article will contribute to a 'Learning with reflection' CPD activity Patients with atrial fibrillation (AF) are at high risk of premature mortality and a range of other adverse cardiovascular and thromboembolic outcomes. The availability of newer oral anticoagulants has broadened therapeutic options beyond vitamin K antagonists, and these are supported increasingly by well-designed, randomised-controlled, outcomes trials. Here, we discuss the results, and implications for practice, of the ENGAGE-AF TIMI-48 and ENSURE-AF trials, that evaluated the Factor Xa inhibitor, edoxaban, in patients with AF. ENGAGE-AF showed that edoxaban 60 mg (reduced to 30 mg in appropriate patients) once daily was as effective as warfarin (dosed to increase INR to 2.0–3.0) in terms of the risk of stroke and systemic embolus, the study primary end point. It also induced less major bleeding and intracranial bleeding than warfarin. Subgroup analyses have given confidence that the therapeutic benefit of edoxaban is present irrespective of age, ethnicity, body mass index, common cardiovascular and other comorbidities, such as prior stroke or transient ischaemic attack, coronary artery disease, heart failure (including treatment with digoxin or amiodarone), renal dysfunction, cancer, and increased risk of falling. ENSURE-AF demonstrated that edoxaban is an appropriate alternative to warfarin/enoxaparin for patients with AF undergoing cardioversion, including immediate cardioversion guided by transoesophageal echocardiography....

This article will contribute to a 'Learning with reflection' CPD activity The randomised, double-blind ENGAGE-AF TIMI-48 trial evaluated the Factor Xa inhibitor edoxaban at a ‘low-dose’ of 30 mg (reduced to 15 mg in appropriate patients) and a ‘high-dose’ of 60 mg (reduced to 30 mg in appropriate patients) once daily in comparison with warfarin over a median treatment period of 2.8 years in a population of 21,105 patients with atrial fibrillation (AF) and risk factors for stroke. The ‘low-dose’ regimen was not subsequently submitted for regulatory approval, and this article will discuss the approved high-dose edoxaban regimen. Either dose level of edoxaban was non-inferior to warfarin for prevention of cardiovascular events related to stroke and systemic embolism. Reduced risk of major bleeding with edoxaban included significantly less intracranial bleeding and haemorrhagic stroke compared with warfarin. Importantly, this therapeutic profile was maintained in older patients, and patients with a prior history of cerebrovascular disease, which are themselves major risk factors for stroke, in addition to other key patient subgroups based on prior or current anticoagulant or antiplatelet therapy, and race/ethnicity. The results of ENGAGE-AF TIMI-48 demonstrated that edoxaban is as effective as warfarin for the prevention of stroke and other cardiovascular or embolic events in people with AF, with a significantly reduced risk of major bleeds....

This article will contribute to a 'Learning with reflection' CPD activity The Hokusai-VTE study randomised 8,240 patients with venous thromboembolism (VTE) to the non-vitamin K antagonist oral anticoagulant (NOAC), edoxaban (after initial treatment with enoxaparin or unfractionated heparin for ≥5 days), with warfarin (given concurrently with heparin) for at least three months and up to 12 months. The dose of edoxaban was 60 mg once daily, with 50% dose reduction to 30 mg for defined patient subgroups. Edoxaban was non-inferior to warfarin for the primary end point of recurrence of VTE, and was superior to warfarin for the main safety end point of major bleeding. The incidence of any bleeding was also lower for edoxaban versus warfarin. The therapeutic profile of edoxaban was maintained in important patient subgroups, including those based on the type of VTE (deep vein thrombosis or pulmonary embolism), the dose level or duration of edoxaban administered, age, the presence/absence of right heart dysfunction, comorbidity and polypharmacy. Low-risk patients could be managed successfully at home, with no increased risk of adverse outcomes. These data establish edoxaban as an alternative to vitamin K antagonist in the management of VTE....

This article will contribute to a 'Learning with reflection' CPD activity Clinical trials and meta-analyses have documented the therapeutic advantages of non-vitamin K oral anticoagulants (NOACs) in patients with venous thromboembolism (VTE) and those at risk of strokes. Additional analyses from these trials have demonstrated their effectiveness and safety in a broad range of common patient subgroups. The convenient administration regimen of NOACs, including the once-daily administration schedule of edoxaban (following ≥5 days of parenteral anticoagulant in VTE indications), and lack of need for routine anticoagulation monitoring may contribute to improved delivery of anticoagulant therapy, compared with warfarin, especially for younger, active patients and those with multiple comorbidities at risk of polypharmacy. It is essential that NOACs are dosed appropriately, according to individual patient characteristics; underdosing due to misplaced fear of bleeding events with these agents may increase the risk of subsequent stroke. Currently, NOACs are underused in routine clinical care, and barriers to their prescription should be removed to encourage greater use of this evidence-based treatment....