Antiarrhythmic drugs — structured written assessment

SAQ 1 (10 marks)

Practice scenario. A 64-year-old man had a myocardial infarction four years ago and has coronary artery disease, with LVEF 55% and no heart failure. He has symptomatic paroxysmal AF and needs long-term rhythm control. His creatinine clearance is 50 mL/min, potassium 4.4 mEq/L and baseline QT interval 420 msec.^[1][2]

1. Why should he not receive flecainide? Give the ACC/AHA 2023 row with its class, the ESC 2024 exclusion, and the trial evidence the FDA label reports. (2)^[2][1][9]
2. Which ESC 2024 AF long-term rows include him, with class and level? (2)^[1]
3. Sotalol is chosen. List the checks the FDA label requires before the first dose, and where it should be started. (2)^[10]
4. What dosing interval does the FDA label give for his creatinine clearance, and what do ACC/AHA 2023 Table 23 and ESC 2022 VA Table 8 say about sotalol in kidney disease? (2)^[10][2][3]
5. Give two QT rules for sotalol from the FDA label. (2)^[10]

Model answers — SAQ 1

1. ACC/AHA 2023: in patients with previous MI and/or significant structural heart disease, including HFrEF, flecainide and propafenone should not be given because of the risk of worsening heart failure, potential proarrhythmia and increased mortality (COR 3: Harm, LOE B-R); ESC 2024 AF recommends flecainide or propafenone (Class I, Level A) excluding patients with impaired LV systolic function, severe LV hypertrophy or coronary artery disease, so he falls outside that row (1 mark).^[2][1] The flecainide label reports CAST, a long-term, multicentre, randomised, double-blind study in patients with asymptomatic non-life-threatening ventricular arrhythmias after an MI more than six days but less than two years earlier: mortality or non-fatal cardiac arrest was 5.1% with flecainide against 2.3% with placebo, over an average 10 months of treatment (1 mark).^[9]
2. Dronedarone is recommended for AF requiring long-term rhythm control, including patients with HFmrEF, HFpEF, ischaemic heart disease or valvular disease, to prevent recurrence and progression of AF (Class I, Level A) (1 mark).^[1] Sotalol may be considered with normal LVEF or coronary artery disease, to prevent recurrence and progression of AF, but requires close monitoring of QT interval, serum potassium, renal function and other proarrhythmia risk factors (Class IIb, Level A) (1 mark).^[1]
3. A baseline ECG for the QT interval; measure and normalise serum potassium and magnesium; measure serum creatinine and calculate creatinine clearance to set the dosing interval (1 mark).^[10] Hospitalise for at least 3 days, or until steady state, in a facility with cardiac resuscitation and continuous ECG monitoring; ACC/AHA 2023 says that in AF it is reasonable to start sotalol in a facility that can provide continuous ECG monitoring, CrCl calculation and cardiac resuscitation, given the potential for proarrhythmia and bradycardia (COR 2a, LOE B-R) (1 mark).^[10][2]
4. FDA label: creatinine clearance 30–59 mL/min means a dosing interval of 24 hours, starting at 80 mg (1 mark).^[10] ACC/AHA 2023 Table 23 gives 80 mg once daily for 3 days, then 80–160 mg once daily, for CrCl 40–60 mL/min and lists CrCl under 40 mL/min as a contraindication; ESC 2022 VA Table 8 lists CrCl under 30 ml/min as a contraindication (1 mark).^[2][3]
5. The dose may be increased by 80 mg per day every 3 days provided QTc is under 500 msec, and QTc is monitored 2 to 4 hours after each uptitration (1 mark).^[10] If the QT interval prolongs to 500 msec or more, reduce the dose, lengthen the dosing interval or discontinue; for AF, a baseline QT over 450 msec is a contraindication (1 mark).^[10]