Rhythm Control Pharmacotherapy

Rhythm control restores and maintains sinus rhythm with cardioversion, antiarrhythmic drugs or catheter ablation.

It is considered early for symptomatic atrial fibrillation, for first-detected atrial fibrillation of recent onset, for rate-related heart failure and in younger people. The antiarrhythmic drug is chosen by the underlying heart disease.

Anticoagulation is required around every cardioversion: at least 3 weeks before, unless transoesophageal echocardiography excludes thrombus, and for at least 4 weeks after, with long-term treatment decided by stroke risk.

Safety of the choice. Class IC drugs (flecainide, propafenone) are unsafe in coronary disease, heart failure, reduced ejection fraction or marked left ventricular hypertrophy.

Baseline. ECG with QTc, PR interval and QRS width, ejection fraction, creatinine, potassium, magnesium, liver tests and thyroid function.

Pharmacological cardioversion, recent onset under 48 hours, structurally normal heart. Flecainide 200 mg orally if weight is under 70 kg, or 300 mg if 70 kg or over, with an atrioventricular nodal blocker; or flecainide 2 mg/kg intravenously over 10 minutes (maximum 150 mg). Vernakalant 3 mg/kg intravenously over 10 minutes, and 2 mg/kg after 15 minutes if needed (avoid in acute coronary syndrome, severe heart failure or systolic pressure under 100 mmHg).

Structural heart disease or heart failure. Amiodarone 300 mg intravenously over 1 hour, then 900 mg over 24 hours, then oral treatment.

Maintenance, structurally normal heart. Flecainide 50 mg orally twice daily, increased to 100 mg twice daily (maximum 300 mg daily), with a beta blocker. Propafenone 150 mg three times daily, increased to 300 mg twice daily.

Maintenance, coronary disease or hypertension with hypertrophy. Sotalol 40 to 80 mg orally twice daily, increased to 160 mg twice daily, started in hospital with QTc monitoring. Avoid if creatinine clearance is under 40 mL/min or QTc is over 500 ms. Dronedarone 400 mg twice daily with meals, not in permanent atrial fibrillation, heart failure with recent decompensation or severe left ventricular dysfunction.

Maintenance, heart failure. Amiodarone 200 mg orally three times daily for 1 week, 200 mg twice daily for 1 week, then 100 to 200 mg once daily. Baseline thyroid, liver, chest imaging and lung function tests.

Special groups. In pregnancy avoid amiodarone and use electrical cardioversion, with flecainide or sotalol only under specialist care. In older adults start at half dose. In creatinine clearance under 35 mL/min start flecainide at 100 mg daily and avoid sotalol. In hepatic impairment avoid amiodarone and dronedarone in significant disease. In East Africa, amiodarone is used where ablation is not available, and thyroid dysfunction may be missed in iodine-deficient areas.

Monitoring. ECG at start and after each dose change. For flecainide, reduce or stop for QRS widening of over 25% from baseline. For sotalol and dronedarone, stop for QTc over 500 ms or a rise of over 60 ms. Amiodarone needs thyroid and liver tests at 6 months and annually, an annual eye review, and chest imaging if cough or breathlessness appears.

Interactions. Amiodarone raises digoxin (halve the dose), warfarin (reduce the dose by 30% to 50%), and simvastatin (limit to 20 mg). Dronedarone requires dabigatran and edoxaban dose review.

Electrolytes. Keep potassium over 4.0 mmol/L and magnesium over 0.8 mmol/L.

Stopping. Stop a class IC drug for pro-arrhythmia, heart failure or QRS widening. Stop amiodarone for thyroid dysfunction, pulmonary toxicity or hepatotoxicity. Dronedarone is stopped for liver injury.

Common errors. Class IC drugs in coronary disease, starting sotalol outside hospital, no anticoagulation around cardioversion, and no baseline thyroid or liver tests with amiodarone.

Referral and escalation. Refer to cardiology or electrophysiology for failure of one antiarrhythmic drug, heart failure with atrial fibrillation, pre-excitation, or consideration of ablation.