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7.2.4 Antiarrhythmic drugs The aims of long-term rhythm control are to maintain sinus rhythm, improve quality of life, slow the progression of AF, and potentially reduce morbidity related to AF episodes (see Supplementary data online, Additional Evidence Table S19).17,445,574,575 Antiarrhythmic drugs do not eliminate recurrences of AF, but in patients with paroxysmal or persistent AF, a recurrence is not equivalent to treatment failure if episodes are less frequent, briefer, or less symptomatic. Antiarrhythmic drugs also have a role for long-term rhythm control in AF patients that are considered ineligible or unwilling to undergo catheter or surgical ablation. Before starting AAD treatment, reversible triggers should be identified and underlying comorbidities treated to reduce the arrhythmogenic substrate, prevent progression of AF, and facilitate maintenance of sinus Table 13 Antiarrhythmic drugs for sinus rhythm restoration Drug Administration route Initial dosing Subsequent dosing [longterm approach] Acute success rate and time to sinus rhythm Contraindications and precautions Flecainide Oral 200–300 mg [long-term 50−150 mg twice daily] 50%–60% at 3 h and 75%–85% at 6–8 h (3–8 h) • Should not be used in patients with severe structural or coronary artery disease, Brugada syndrome, or severe renal failure (CrCl <35 mL/min/1.73 m2). • Prior documentation of safety and efficacy in an inpatient setting is recommended prior to pill-in-the-pocket use. • An AVN-blocking agent should be administered to avoid 1:1 conduction if transformation to AFL. • Drug infusion should be discontinued in case of QRS widening >25% or bundle branch block occurrence. • Caution is needed in patients with sinus node disease and AVN dysfunction. • Do NOT use for conversion of atrial flutter. Intravenous 1–2 mg/kg over 10 min 52%–95% (Up to 6 h) Propafenone Oral 450–600 mg [long-term 150-300 mg three times daily] 45%–55% at 3 h, 69%–78% at 8 h (3–8 h) Intravenous 1.5–2 mg/kg over 10 min 43%–89% (Up to 6 h) Amiodarone Intravenous (/oral) 300 mg intravenous over 30–60 min 900-1200 mg intravenous over 24 hours (or 200 mg oral three times daily for 4 weeks). [long-term 200 mg oral daily] 44% (8–12 h to several days) • May cause phlebitis (use a large peripheral vein, avoid i.v. administration >24 h and use preferably volumetric pump). • May cause hypotension, bradycardia/ atrioventricular block, QT prolongation. • Only if no other option in patients with hyperthyroidism (risk of thyrotoxicosis). • Consider the broad range of drug interactions. Ibutilide Intravenous 1 mg over 10 min (0.01 mg/kg if body weight <60 kg) 1 mg over 10 min (10–20 min after the initial dose) 31%–51% (30–90 min) in AF 60–75% in AFL (60 min) • Should be used in the setting of a cardiac care unit as it may cause QT prolongation and torsades de pointes. • ECG monitoring for at least 4 h after administration to detect any proarrhythmic effects. • Should not be used in patients with prolonged QT, severe LVH, or low LVEF. Vernakalant Intravenous 3 mg/kg over 10 min (maximum 339 mg) 2 mg/kg over 10 min (10–15 min after the initial dose) (maximum 226 mg) 50% within 10 min • Should not be used in patients with arterial hypotension (SBP <100 mmHg), recent ACS (within 1 month), NYHA III or IV HF, QT prolongation or severe aortic stenosis. • May cause arterial hypotension, QT prolongation, QRS widening, or non-sustained ventricular tachycardia. © ESC 2024 ACS, acute coronary syndromes; AF, atrial fibrillation; AFL, atrial flutter; AVN, atrioventricular node; CrCl, creatinine clearance; ECG, electrocardiogram; HF, heart failure; LVEF, left ventricular ejection fraction; LVH, left ventricular hypertrophy; NYHA, New York Heart Association; QT, QT interval; SBP, systolic blood pressure. Long-term dosage for maintenance of sinus rhythm is indicated in [square brackets]. Long-term oral dosing for dronedarone is 400 mg twice daily, and for sotalol 80-160 mg twice daily. ESC Guidelines 3357 Downloaded from academic.oup.com/eurheartj/article/45/36/3314/7738779 by guest on 07 October 2026