Rate Control Therapy Evaluation in Permanent Atrial Fibrillation (RATE-AF) (RATE-AF)
Permanent Atrial Fibrillation
About this trial
This is an interventional treatment trial for Permanent Atrial Fibrillation focused on measuring Atrial fibrillation, Quality of life, Left ventricular ejection fraction, Diastolic function, Echocardiography, Beta-blockers, Digoxin
Eligibility Criteria
Inclusion Criteria:
- Adult patients aged 60 years or older, able to provide informed written consent
- Permanent AF, characterised (at time of randomisation) as a physician decision for rate-control with no plans for cardioversion, anti-arrhythmic medication, or ablation therapy
- Symptoms of breathlessness (New York Heart Association Class II or more)
- Able to provide written, informed consent
Exclusion Criteria:
- Established indication for beta-blocker therapy, e.g. survived myocardial infarction in the last 6 months
- Known contraindications for therapy with beta-blockers or digoxin, e.g. a history of severe bronchospasm that would preclude use of beta-blockers, or known intolerance to these medications
- Baseline heart rate <60 bpm
- Known intolerance of beta-blockers or digoxin
- A history of severe bronchospasm (e.g. due to asthma) that would preclude use of beta-blockers
- Baseline heart rate <60 bpm
- History of second or third-degree heart block
- Supraventricular arrhythmias associated with accessory conducting pathways (e.g. Wolff-Parkinson-White syndrome) or a history of ventricular tachycardia or fibrillation
- Planned pacemaker implantation, pacemaker-dependent rhythm or history of atrioventricular node ablation
- Decompensated heart failure (evidenced by need for intravenous inotropes, vasodilators or diuretics) within 14 days prior to randomisation
- A current diagnosis of hypertrophic cardiomyopathy, myocarditis or constrictive pericarditis
- Received or on waiting list for heart transplantation
- Initiation of cardiac resynchronization therapy (with/without defibrillator) within 6 months prior to randomisation
- Intravenous infusions for heart failure (inotropes, vasodilators or diuretics) within 7 days prior to randomisation
- A current diagnosis of hypertrophic cardiomyopathy, myocarditis or constrictive pericarditis
- Received or on waiting list for heart transplantation
- Receiving renal replacement therapy
- Major surgery, including thoracic or cardiac surgery, within 3 months of randomisation
- Severe, concomitant non-cardiovascular disease (including malignancy) that is expected to reduce life expectancy
Sites / Locations
- City Hospital
- Queen Elizabeth Hospital
Arms of the Study
Arm 1
Arm 2
Active Comparator
Active Comparator
Beta-blocker
Digoxin
In Group B, oral bisoprolol will be commenced at either 1.25mg, 2.5mg or 5mg according to the treatment schedule and uptitrated, as required, to 15mg daily. Recommended additional therapy in this arm includes diltiazem. Use of digoxin is explicitly discouraged but will not terminate participation in the study. If intolerance to bisoprolol occurs, investigators will be advised to try an alternate beta-blocker of their choosing (typically carvedilol, nebivolol, or metoprolol) at equivalent dosage.
In Group A, the maintenance dose of oral digoxin will be either 62.5mcg or 125mcg according to the pre-defined treatment schedule and uptitrated, as required, to 250mcg daily. A single loading dose of four tablets (250 or 500mcg according to target maintenance dose) will be prescribed in digoxin-naïve participants, where necessary. Recommended additional therapy in this arm includes the calcium-channel blocker diltiazem. Use of beta-blockers is explicitly discouraged but will not terminate participation in the study.