This program is a comprehensive evaluation of rheumatic valvular heart disease (RVHD), Atrial fibrillation (AF)/flutter and stroke. A prospective, randomized, parallel group, open-label clinical trial of rivaroxaban versus standard vitamin K antagonists (VKA) therapy to evaluate non-inferiority of rivaroxaban to VKA, with testing for superiority if non-inferiority is satisfied.
Non-Inferiority Trial of rivaroxaban versus VKAs: 4,500 patients Inclusion Criteria: 1. RVHD diagnosed by echocardiography at any time prior to enrollment 2. Age ≥18 3. Increased risk of stroke by any of the following 1. CHA2DS2-VASc score ≥ 2 OR 2. Moderate/Severe mitral stenosis with valve area ≤2.0 cm2 OR 3. Left atrial spontaneous echo contrast OR 4. Left atrial thrombus 4. Heart Rhythm a) AF or Flutter should be documented on baseline 12-lead ECG, or on a previous 12-lead ECG, Holter monitor, in-hospital ECG rhythm strip or Pacemaker or ICD electrogram. Treatment: Patients will be randomized either to receive rivaroxaban or any approved VKA. Treatment will be open-label. 1. Rivaroxaban Arm * Rivaroxaban 20 mg once daily * Rivaroxaban 15 mg once daily (for patients with an creatinine clearance ≥15 and \<50 ml/min) 2. VKA Arm * Any VKA approved for use in the participating country * VKA titrated to achieve an INR of 2.0-3.0
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
4,565
Rivaroxaban is non-inferior to VKAs for the prevention of stroke or systemic embolism in patients with AF/flutter and RVHD and potentially superior to VKAs.
Time from randomization to the first occurrence of vascular death or death of unknown cause, stroke, myocardial infarction or systemic embolism
Vascular death or death of unknown cause, stroke, myocardial infarction or systemic embolism
Time frame: Approximately 4 years
Time from randomization to the first occurrence of composite of stroke or systemic embolism
Composite of stroke or systemic embolism
Time frame: Approximately 4 years
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