Rivaroxaban Once Daily Versus Dose-adjusted Vitamin K Antagonist on the Biomarkers in Acute Decompensated Heart Failure and Atrial Fibrillation (ROAD HF-AF)

Yonsei University150 enrolled

Overview

Vitamin K antagonists (VKAs) are used to reduce the risk of stroke (cerebral vascular dysfunction) in AF patients. However, VKAs interact with drugs/food and the drug level is influenced by worsening of renal function, liver congestion or hemodynamic alterations in acute decompensated heart failure (ADHF). New oral anticoagulants (rivaroxaban, apixaban, dabigatran) are alternatives to VKA, such as warfarin. In post hoc analysis of ROCKET AF trial, 63.7% patients had HF and treatment-related outcomes were similar in patients with and without HF (Circulation HF. 2013; 6:740-7). So rivaroxaban 20 mg daily (or 15 mg daily in patients with creatinine clearance 30-49 mL/min) was safe in nonvalvular AF patients with HF. However, the clinical effect and safety of rivaroxaban were largely unknown in acute decompensated heart failure (ADHF) patients with atrial fibrillation (AF). ROAD HF-AF is the exploratory study to assess the change of surrogate markers (hsTn, d-dimer) when treated with rivaroxaban vs. warfarin and to strengthen the basis for future biomarker-based therapy in ADHF patients

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

150

Conditions

Acute Heart Failure

Interventions

Eligibility

Sex: ALLMin age: 19 Years

Medical Language ↔ Plain English

Inclusion Criteria:Hospitalized patients with a primary diagnosis of ADHF with AF One of the following criteria and LVEF ≤ 40% (at least 1 year before admission or admission) 1. dyspnea at rest 2. tachypnea; a respiratory rate \> 20/min 3. rales 4. pulmonary edema on chest X-ray Exclusion Criteria: 1. History of increased bleeding risk (like ROCKET AF exclusion criteria) 2. Contraindication to anti-coagulation therapy 3. ACS diagnosis 4. Hospitalization plan for PCI, coronary artery bypass graft surgery, other cardiac invasive interventions (e.g. catheter ablation, pacemaker, CRT, ICD implantation) 5. Currently on dual anti-platelet therapy (aspirin + ADP receptor antagonist) or single antiplatelet therapy with a novel AP (e.g. Ticagrelor, Prasugrel) 6. Cardiogenic shock (systolic blood pressure, SBP, \< 80 mmHg) 7. Patients with CrCl \< 30 ml/min using creatinine-based CKD-EPI equations 8. Elevated liver enzymes (3 times over upper reference limit) or liver cirrhosis 9. Uncontrolled hypertension (SBP \> 180 mmHg) 10. Allergy, adverse drug reaction, hypersensitivity to rivaroxaban or warfarin 11. Life expectancy \< 6 months (e.g. metastatic malignancy) 12. Pregnancy, or women of childbearing age

Outcomes

Primary Outcomes

the change of high sensitive troponin

The maximum hsTn value change from baseline to during hospitalization

Time frame: Baseline to 72 hours

Secondary Outcomes

1) the change of hish sensitive troponin

1\) The change from baseline in hsTn on Day2, day4, day7 (or discharge), and follow-up visits at 1 month, 6 months

Time frame: 1) On admission, hospital day #2, hospital day #4, hospital day #7 or discharge, 1 month/6month after discharge

2) the change of D-dimer

2\) D-dimer change from baseline during hospitalization (day2, day4, day7 or discharge) \& follow-up visits at 1, 6 months

Time frame: 2) On admission, hospital day #2, hospital day #4, hospital day #7 or discharge, 1 month/6month after discharge

3) the change of NT-proBNP

3\) TAT complex, PAI-1, hsCRP, NT-proBNP, sST2, galectin-3, cystatin C, NGAL, NAG change from baseline to day7 or discharge \& 1,6 months after discharge

Time frame: 3) On admission, hospital day #7 or discharge, 1 month/6month after discharge

4) bleeding event

4\) Incidence proportion and rate of major/minor bleeding during the study

Time frame: 4) On admission, hospital day #2, hospital day #4, hospital day #7 or discharge, 1 month/3month/6month after discharge

5) hospital stay

5\) Length of hospital stay

Time frame: 5) The duration of hospital stay, average 7 days

6) all-cause mortality

6\) Incidence proportion of in-hospital all-cause death cases

Time frame: 6) 6 months after hospitalization

7) all-cause hospitalization & mortality

7\) Time to the first composite event of all-cause mortality or cardiovascular re-hospitalization

Time frame: 7) 6 months after hospitalization