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CLINICAL STATEMENTS AND GUIDELINES

Circulation. 2024;149:e1–e156. DOI: 10.1161/CIR.0000000000001193 January 2, 2024 e81

Joglar et al 2023 Guideline for the Diagnosis and Management of Atrial Fibrillation

3 The PITP strategy—a high dose of a class IC agent

(flecainide 200-300 mg or propafenone 450-600 mg, with an atrioventricular nodal blocker)—can be considered for patients who experience infrequent episodes of symptomatic AF and do not prefer chronic antiarrhythmic therapy. Class IC agents are generally administered with concomitantly atrioventricular nodal blocking agents to mitigate risk of rapidly conducting AFL. Because of the risk of adverse effects and proarrhythmia with high-dose IC agents, inpatient initiation of PITP has been studied. In 1 trial evaluating the safety of outpatient PITP therapy after initiation as an inpatient, 58 of 268 (22%) patients experienced transient hypotension, 1:1 and 2:1 AFL, and symptomatic bradycardia.9 In a prospective study of 43 patients who presented to the emergency department for initiation of PITP,10 sinus rhythm was restored in 30 patients; 13 patients remained in AF, and/or had symptomatic hypotension, converted to rapid AFL requiring cardioversion, or experienced a syncopal conversion pause. In a retrospective cohort13 study of 273 patients initiating PITP (62% inpatient), 7 patients experienced significant adverse events, including syncope, symptomatic bradycardia/hypotension, and organization to 1:1 AFL—2 of 7 of these patients initiated PITP as an inpatient, and 2 patients required permanent pacemakers for bradycardia.

8.3.3. Antiarrhythmic Drug Follow-Up Antiarrhythmic drugs are associated with important adverse effects, and monitoring is recommended to assess their efficacy for maintaining sinus rhythm and for prevention and/or early detection of adverse events.

Drug Loading Dose Maintenance Dose Primary Route(s) of Elimination Elimination Half-Life Mechanism of Action Major Adverse Effects Important Pharmacokinetic Drug Interactions Flecainide N/A 50-300 mg/d PO divided q 8-12 h Liver (70%) Kidney (30%)¶ 12-27 h Inhibits INa Atrial flutter AV block Dizziness Dyspnea Exacerbation of HFrEF Headache Nausea QT prolongation VT Visual disturbances Flecainide is a substrate for CYP2D6 These drugs may increase plasma flecainide concentrations: Amiodarone Duloxetine Fluoxetine Paroxetine Propafenone N/A 150-300 mg PO q 8 h, ER 225-425 PO q 12 h Liver 9 h Inhibits INa Atrial flutter Bradycardia AV block Dizziness Dyspnea Exacerbation of HFrEF Nausea Taste disturbances VT Visual disturbances Propafenone is a substrate for CYP2D6 These drugs may increase plasma propafenone concentrations: Fluoxetine Paroxetine Propafenone may increase plasma digoxin concentrations Propafenone may increase plasma warfarin concentrations Sotalol CrCl >60 mL/ min: 40-80 mg twice daily for 3 d CrCl: 40-60 mL/min: 80 mg once daily for 3 d CrCl <40 mL/ min: Contraindicated CrCl >60 mL/ min: 80-160 mg twice daily CrCl: 40-60 mL/min: 80- 160 mg once daily CrCl <40 mL/ min: Contraindicated Kidney 12 h Inhibits IKr Beta blocker d-Sotalol augments late INa AV block Bradycardia Bronchospasm Diarrhea Exacerbation of HFrEF Fatigue Nausea and vomiting QT prolongation TdP None *Moderate inhibitor: Causes a 2-fold to <5-fold increase in AUC or a 50% to 80% decrease in clearance. †Mild inhibitor: Causes a ≥1.25-fold but <2-fold increase in AUC or a 20% to 50% decrease in clearance. ‡Lovastatin doses should not exceed 40 mg daily in patients taking amiodarone. §Simvastatin doses should not exceed 20 mg daily in patients taking amiodarone. ‖Simvastatin doses should not exceed 10 mg daily in patients taking dronedarone. ¶Percentage of a dose excreted unchanged in urine. AF indicates atrial fibrillation; AUC, area under the plasma concentration versus time curve; AV, atrioventricular; CrCl, creatinine clearance; CYP, cytochrome P-450; ER, extended release; HFrEF, heart failure with reduced ejection fraction; IV, intravenous; N/A, not applicable; NAPA, N-acetylprocainamide; p-gp, p-glycoprotein; PO, orally; TdP, torsades de pointes; and VT, ventricular tachycardia.

Table 23.  Continued

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