Flecainide: Current status and perspectives in arrhythmia management

Table 1 Reversion rate of recent-onset atrial fibrillation to sinus rhythm in clinical trials evaluating the conversion efficacy of oral or intravenous flecainide

Clinical trial	Patients in flecainide arm	AF duration	Formulation	Reversion rate
Capucci et al[38]	22 patients	≤ 7 d	Single oral dose (300 mg)	8 h → 91%
				24 h → 95%
Donovan et al[39]	51 patients	≤ 3 d	iv (2 mg/kg-max 150 mg)	1 h → 57%
				6 h → 67%
Donovan et al[40]	34 patients	≤ 3 d	iv (2 mg/kg-max 150 mg)	2 h → 59%
				8 h → 68%
Boriani et al[41]	69 patients	< 8 d	Single oral dose (300 mg)	1 h → 13%
				3 h → 57%
				8 h → 75%
Martínez-Marcos et al[42]	50 patients	≤ 2 d	iv (2 mg/kg followed by 1 mg/kg at 8 h if not SR)	1 h → 58%
				8 h → 82%
				12 h → 90%
Romano et al[43]	138 patients	≤ 3 d	Intravenous	1 h → 73%
				3 h → 80%
				6 h → 86%
				24 h → 90%

AF: Atrial fibrillation; SR: Sinus rhythm.

Table 2 Flecainide for prevention of atrial fibrillation recurrences - Randomized controlled clinical trials

Clinical trial	Patient population	Compared treatments	Endpoint of AF recurrence	Results	Comments
Steinbeck et al[44]	45 patients Paroxysmal AF	Quinidine + digoxin Flecainide + digoxin Digoxin	AF recurrence at 12 mo	Flecainide and digoxin superior to other regimens and safer than quinidine and digoxin	Quinidine is practically not used any more for sinus rhythm maintenance
Anderson et al[45]	64 patients Paroxysmal AF	Flecainide (median daily dose: 300 mg) Placebo	Patients without AF recurrences Time to first AF recurrence Time interval between AF recurrences	Flecainide superior to placebo Five-fold increase in time to first recurrence Four-fold increase in time interval between attacks Significantly increased percentage of patients free of AF recurrences Adverse cardiac events in 11% of patients during flecainide therapy	Transtelephonic monitoring Double-blind randomized crossover trial (8-wk observation period) Daily flecainide dose > 300 mg in 29% of patients
van Wijk et al[49]	26 patients Paroxysmal AF	Flecainide (200-300 mg daily) Quinidine (1.0-1.5 daily)	AF recurrence during 3-mo follow-up period	Flecainide superior to quinidine in the lower dosing regimen Flecainide similar efficacy to quinidine in higher dosing regimen	20% discontinuation rate with higher quinidine dosing regimen FU with 24-h Holter at the end of each month
van Gelder et al[46]	81 patients Persistent AF/flutter	Flecainide Placebo	AF recurrence at 12 mo	Flecainide superior to placebo in preventing arrhythmia recurrences	Difficult to treat patients (mean AF duration: 12 mo)
Pietersen et al[47]	43 patients Paroxysmal AF/flutter	Flecainide (300 mg/d) Placebo	AF recurrence at 3 mo	Flecainide superior to placebo in preventing arrhythmia recurrences Adverse effects in 74% of patients treated with flecainide	Tolerable adverse events in flecainide group (only 2 withdrawals) One episode of sudden death
Carunchio et al[48]	66 patients Paroxysmal AF	Flecainide Sotalol Placebo	AF recurrence at 1, 3, 6 and 12 mo	Flecainide similar efficacy to sotalol and superior to placebo
Aliot et al[51]	97 patients Paroxysmal AF/flutter	Flecainide (100-300 mg/d) Propafenone (600-1200 mg/d)	AF recurrence at 12 mo	Flecainide similar efficacy to propafenone Treatment discontinuation rate lower with flecainide (38% vs 53%, P = 0.079)	Multicenter, randomized, open-label study One episode of sudden death in the propafenone group
Chimienti et al[52]	200 patients Paroxysmal AF	Flecainide (200-300 mg/d) Propafenone (450-900 mg/d)	Palpitation recurrence on days 15, 30, 90, 180, 270, and 360	Flecainide similar efficacy to propafenone Similar rate of adverse cardiac and noncardiac events	Multicenter, open label, randomized, parallel study Suboptimal follow-up of AF recurrence
Naccarelli et al[50]	239 patients Paroxysmal AF	Flecainide (100-300 mg/d) Quinidine	AF recurrence at 12 mo	Flecainide similar efficacy to quinidine Flecainide better tolerated than quinidine	Multicenter, open label, randomized, parallel study Self-reporting of symptomatic AF recurrences (diary recording)
Gulizia et al[54]	176 pacemaker recipients with sinus node disease and paroxysmal AF	Ic AAD (flecainide or propafenone) Amiodarone	Primary endpoint: time to first occurrence of death, atrial cardioversion, cardiovascular hospitalization, or change of AAD	Class Ic AADs non-inferior to amiodarone in terms of the primary endpoint. Similar efficacy in freedom from AT recurrences based on post-hoc analyses	One patient experienced sudden cardiac death in flecainide group Capability of continuous rhythm monitoring by pacemaker AF recurrence and burden not included in primary endpoint
Kirchhof et al[56]	635 patients Persistent AF	Short-term flecainide Long-term flecainide Placebo	Time to first recurrence of persistent atrial fibrillation or death from any cause	Flecainide superior to placebo Short-term flecainide not non-inferior to long-term	Largest, prospective randomized clinical trial Meticulous follow-up

AF: Atrial fibrillation; AAD: Antiarrhythmic drug; AT: Atrial tachycardia.