objectives: The primary aim of APIXBRAIN-HF Trial is to explore the effects of apixaban on brain protection in patients with sinus rhythm and heart failure

Primary / Secondary Endpoint

1. New occurrence of brain pathology 1) Cortical cerebral microinfarcts 2) Silent lacunar infarction 3)Progression of white matter hyperintensities
2. Secondary endpoint 1) The change of cognitive function evaluated by MMSE-2 2) Individual variable of primary endpoint
3. Safety Endpoint Evaluation 1) Cerebral microbleeds on imaging

This study is a double-blind, parallel-group, and randomization study. The investigators will enroll the patients with heart failure who demonstrated LV systolic dysfunction (LVEF ≤ 40%) and sinus rhythm with a CHA2DS2-VASc score ≥ 3. All patients would be randomly assigned to either the apixaban group or placebo group. Patients assigned to the apixaban group will receive 5mg bid or 2.5mg bid (patients with at least 2 of the following characteristics: aged≥80-year, bodyweight ≤60kg, serum creatinine 1.5 ml/dL) and patients in the placebo group will receive a placebo of apixaban. Both drugs will be maintained for 6 months. During the study period, all patients will be carefully monitored for thromboembolic events, including stroke. At the beginning of the study and 6 months after randomization, 3T Brain MRI and MMSE-2 test will be performed to identify changes in brain structure and cognitive function.

Inclusion Criteria:

• Patients aged over 19 years old

• Patients with sinus rhythm

• Newly diagnosed of heart failure or aggravated heart failure symptom

  1. Dyspnea (≥ NYHA II)
  2. plasma BNP ≥ 200 pg/ml or NT-proBNP ≥ 800 pg/ml

• LV systolic dysfunction on echocardiography within 3 month of enrollment

  1) LVEF ≤ 40%

• Those with CHA2DS2-VASc ≥ 3

• Modified Rankin Score ≤ 4

Exclusion Criteria:

• Patients already subscribed warfarin or antiplatelet therapy or have clear indication for warfarin or antiplatelet therapy
• At high risk for bleeding
• Patients with atrial fibrillation
• Estimated glomerular filtration rate (CKD-EPI formula) < 15 ml/min/1.73 m2)
• Recent stroke or brain hemorrhage (within 3 months)
• Patients who was diagnosed of myocardial infarction or who has plan to PCI/CABG at enrollment
• End stage heart failure with life expectancy ≤ 6 months
• Patients with bed ridden status (Modified Rankin Score ≥ 5)
• Patients with liver dysfunction (AST, ALT > 2 times of upper normal limits or total bilirubin > 1.5 of upper normal limits)
• At of pregnancy or breastfeeding
• Patients who disagree with the use of medically acceptable contraception during the clinical trial period
• Patients with contraindication of apixaban