Rate Control Therapy Evaluation in Permanent Atrial Fibrillation (RATE-AF)
Condition: Permanent Atrial Fibrillation
MeSH terms: Atrial Fibrillation
Intervention: Bisoprolol; Digoxin
Intervention description: Drug intervention; Drug intervention
Intervention MeSH terms: Digoxin; Bisoprolol
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 161.0
Sex: All
Minimum age: 60 Years
Healthy volunteers: No
Keywords: Atrial fibrillation; Quality of life; Left ventricular ejection fraction; Diastolic function; Echocardiography; Beta-blockers; Digoxin

Summary:

      Atrial fibrillation is a common heart rhythm disturbance, causing important discomfort for
      patients, a high risk of stroke, frequent hospital admissions and a two-fold increase in
      death. The number of patients with this condition are expected to double in the next 20
      years. Medications to control heart-rate are used in the majority of patients, although the
      choice of agent is often guided by local preference rather than evidence from controlled
      trials. Despite the fact that patients with atrial fibrillation have high rates of other
      cardiac conditions such as heart failure, clinicians have insufficient evidence to
      personalise the use of different therapies. This feasibility study will allow us to develop a
      range of methods that can characterise patients according to the pumping and relaxing
      function of the heart, the burden of symptoms and to identify new blood markers. In this way,
      the investigators hope to improve clinical practice guidelines, allowing doctors to prescribe
      appropriate treatments for the right patients.

      The research will be focused around a randomised trial of two medication strategies,
      providing much-needed data on the comparison of digoxin and beta-blockers (two commonly-used
      drugs in patients with atrial fibrillation). It will also allow us to identify the best way
      to record patient-reported quality of life and develop robust techniques to determine heart
      function using non-invasive imaging, facilitating the conduct of a large-scale clinical
      trial. The key objectives of the research programme are to define the optimal medications for
      patients with atrial fibrillation and identify the most valid, reproducible and
      cost-effective methods to examine patients. The ultimate aim of the project is to improve
      clinical outcomes in atrial fibrillation, benefiting patients, the National Health Service
      and the global community.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Adult patients aged 60 years or older, able to provide informed written consent

          2. 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

          3. Symptoms of breathlessness (New York Heart Association Class II or more)

          4. Able to provide written, informed consent

        Exclusion Criteria:

          1. Established indication for beta-blocker therapy, e.g. survived myocardial infarction
             in the last 6 months

          2. 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

          3. Baseline heart rate <60 bpm

          4. Known intolerance of beta-blockers or digoxin

          5. A history of severe bronchospasm (e.g. due to asthma) that would preclude use of
             beta-blockers

          6. Baseline heart rate <60 bpm

          7. History of second or third-degree heart block

          8. Supraventricular arrhythmias associated with accessory conducting pathways (e.g.
             Wolff-Parkinson-White syndrome) or a history of ventricular tachycardia or
             fibrillation

          9. Planned pacemaker implantation, pacemaker-dependent rhythm or history of
             atrioventricular node ablation

         10. Decompensated heart failure (evidenced by need for intravenous inotropes, vasodilators
             or diuretics) within 14 days prior to randomisation

         11. A current diagnosis of hypertrophic cardiomyopathy, myocarditis or constrictive
             pericarditis

         12. Received or on waiting list for heart transplantation

         13. Initiation of cardiac resynchronization therapy (with/without defibrillator) within 6
             months prior to randomisation

         14. Intravenous infusions for heart failure (inotropes, vasodilators or diuretics) within
             7 days prior to randomisation

         15. A current diagnosis of hypertrophic cardiomyopathy, myocarditis or constrictive
             pericarditis

         16. Received or on waiting list for heart transplantation

         17. Receiving renal replacement therapy

         18. Major surgery, including thoracic or cardiac surgery, within 3 months of randomisation

         19. Severe, concomitant non-cardiovascular disease (including malignancy) that is expected
             to reduce life expectancy