Efficacy and Safety of Edoxaban in Patients With Atrial Fibrillation and Mitral Stenosis

A Randomized, Open, Phase 2 Study to Evaluate the Efficacy and Safety of Edoxaban in Patients With Atrial Fibrillation and Mitral Stenosis

This study aims to compare the efficacy and safety of the edoxaban and the warfarin in atrial fibrillation patients with mitral stenosis.

The study design is a multicenter, randomized, open-label, investigator initiated phase 2 trial. The patients were randomly assigned to Edoxaban or Warfarin groups. Primary outcome was a composite of stroke and systemic arterial thromboembolism. The safety outcome was major bleeding.

Non-vitamin K antagonist oral anticoagulants (NOACs) are generally recommended as 1st line therapy for oral anticoagulant in patients with atrial fibrillation (AF). But, the efficacy and safety of NOAC in AF patients with prosthetic mechanical heart valves or moderate to severe mitral valve stenosis have not been proven, and the guidelines recommend vitamin K antagonist (VKA) administration to those patient groups. This trial aims to compare the efficacy and safety of the edoxaban and the warfarin in AF patients with moderate to severe mitral valve stenosis.

Edoxaban in patients with aTrial fibrillation and MItral Stenosis (ERTEMIS) trial is a multicenter, randomized, open-label, investigator initiated phase 2 trial. The patients were randomly assigned to Edoxaban or Warfarin groups. The primary efficacy outcome is a composite of stroke and systemic arterial thromboembolism. The secondary efficacy outcomes are each component of the primary efficacy outcomes and death from any cause. The safety outcome was major bleeding.

• Inclusion criteria

  • 18 < Age < 80
  • AF diagnosed by ECG at any time prior to enrollment
  • Moderate or severe mitral valve stenosis diagnosed by echocardiography at any time prior to enrollment

• Exclusion criteria

  • Refusal to consent

  • Transient AF due to reversible cause (Postoperative, ongoing systemic inflammation, thyrotoxicosis)

  • Patients undergoing mechanical valve replacement

  • Coagulopathy

  • Hepatic impairment with significant bleeding risk

  • High bleeding risk due to following disease or condition diagnosed within 1 month prior to randomization

    • GI ulcer or bleeding, Esophageal or gastric varix, Malignancy, Brain or cord injury, Surgery for brain, spinal cord, opthalmic, Intracranial hemorrhage, Arteriovenous malformation, Vascular aneurysms, Brain or spinal vascular disorder

  • Stroke, Systemic arterial thromboembolism, Acute myocardial infarction diagnosed within 14 days prior to randomization

  • End stage kidney disease (CrCL < 15mL/min) or Dialysis

  • Severe hypertension

  • Alcohol abuse or other psychiatric disease

  • Epidural puncture or anesthesia

  • Pulmonary thromboembolism with hemodynamical instability requiring thrombolysis or thrombectomy

  • Pregnant or lactating women

  • Allergy to edoxaban or warfarin

  • Ongoing need for other anticoagulant or clarithromycin, rifampin)

  • Participants for other trials within 1 month prior to enrollment

  • Other patients to be inappropriate to participate in the trial determined by the investigator