Flecainide Group Research Articles

Comparative analysis of antiarrhythmic drugs following atrial fibrillation ablation

Abstract Background Atrial fibrillation (AF) ablation has become an established therapeutic modality for rhythm control. However, the optimal post-ablation pharmacological strategy remains uncertain. The present study addresses this gap by conducting a comparative analysis of four commonly used antiarrhythmic drugs (amiodarone, propafenone, sotalol, and flecainide), both as standalone treatments and in combination with beta blockers, to determine their impact on mortality, hospitalization rates, and AF recurrence. Methods A multi-center, retrospective cohort study was conducted, including patients who underwent successful AF ablation between 20010 to 2020. The study population was divided into groups based on the prescribed antiarrhythmic drug regimen: amiodarone, propafenone, sotalol, flecainide, and respective combinations with beta blockers. Patient demographics, comorbidities, and procedural details were collected. Endpoints included all-cause mortality, hospitalization due to cardiovascular events, MACE and AF recurrence. Results A total of 908 patients were included in this study. The mean age was 66 years old, and 33% (n=297) were female patients. Of 908 patients, 35% (n=316) were prescribed amiodarone, 34% (n=305) propafenone, 8% (n=76) sotalol, and 6%% (n=51) flecainide post AF ablation. Association with beta blockers were observed in 55% (n=496) of cases. Amiodarone group had a 0,3% (n=1) mortality, 9% (n=27) of hospitalizations, 2% (n=5) of major cardiovascular events (MACE) and 32% (n=101) of AF recurrence. Propafenone group had a 1,3% (n=4) mortality, 4% (n=12) hospitalizations, 2% (n=5) of MACE and 27% (n=81) of AF recurrence. Sotalol group had a 4% (n=3) mortality, 6% (n=4) of hospitalizations, 3% (n=2) of MACE and 44% (n=32) of AF recurrence. Flecainide group had 0 cases of death, 2% (n=1) of hospitalization, 0 cases of MACE and 35% of recurrence. Amiodarone is associated with a lower risk of death (p=0,018 OR 0,13). The presence of betablockers did not affect the endpoints, namely, death, hospitalization, MACE or AF recurrence. There were no other statistically significant associations between variables. Conclusion This study evaluated the effectiveness of common antiarrhythmics, such as amiodarone, propafenone, sotalol, and flecainide, with and without beta blockers, in the post-AF ablation setting. In this study, amiodarone showed a lower risk of death. There were no other statistically significant associations between either antiarrhythmic drug and each endpoint. The presence of betablocker therapy did not interfere with the endpoints. The findings contribute to the ongoing discourse on the optimal pharmacological strategy for AF management post-ablation. Further prospective studies with larger sample sizes are warranted to validate and refine these observations, paving the way for evidence-based guidelines in tailoring antiarrhythmic drug regimens for improved patient outcomes

Comparing the Efficacy of Carvedilol and Flecainide on the Treatment of Idiopathic Premature Ventricular Complexes from Ventricular Outflow Tract: A Multicenter, Randomized, Open-Label Pilot Study.

The mechanism of premature ventricular complexes (PVC) occurring in the ventricular outflow tract (OT) is related to an intracellular calcium overload and delayed afterdepolarizations that lead to triggered activity. The guidelines recommend using beta-blockers and flecainide for idiopathic PVCs, but they also acknowledge the limited evidence supporting this recommendation. We conducted a multicenter, randomized, open-label pilot study comparing the effect of carvedilol and flecainide on OT PVC, which are widely used to treat this arrhythmia. Patients with a 24 h Holter recording a PVC burden ≥ 5%, which showed positive R waves in leads II, III, and aVF, and without structural heart disease were enrolled. They were randomly assigned to the carvedilol or flecainide group, and the maximum tolerated dose was administered for 12 weeks. A total of 103 participants completed the protocol: 51 with carvedilol and 52 with flecainide. After 12 weeks of treatment, the mean PVC burden significantly decreased in both groups: 20.3 ± 11.5 to 14.6 ± 10.8% with carvedilol (p < 0.0001) and 17.1 ± 9.9 to 6.6 ± 9.9% with flecainide (p < 0.0001). Both carvedilol and flecainide effectively suppressed OT PVCs in patients without structural heart disease, with flecainide showing a superior efficacy compared to carvedilol.

Long-term outcomes in patients treated with flecainide for atrial fibrillation with stable coronary artery disease

Class 1C antiarrhythmic drugs (AAD) have been associated with harm in patients treated for ventricular arrhythmias with a prior myocardial infarction. Consensus guidelines have advocated that these drugs not be used in patients with stable coronary artery disease (CAD). However, long-term data are lacking to know if unique risks exist when these drugs are used for atrial fibrillation (AF) in patients with CAD without a prior myocardial infarction. In 24,315 patients treated with the initiation of AADs, two populations were evaluated: (1) propensity-matched AF patients with CAD were created based upon AAD class (flecainide, n=1,114, vs class-3 AAD, n=1,114) and (2) AF patients who had undergone a percutaneous coronary intervention or coronary artery bypass graft (flecainide, n=150, and class-3 AAD, n=1,453). Outcomes at 3 years for mortality, heart failure (HF) hospitalization, ventricular tachycardia (VT), and MACE were compared between the groups. At 3 years, mortality (9.1% vs 19.3%, P < .0001), HF hospitalization (12.5% vs 18.3%, P < .0001), MACE (22.9% vs 36.6%, P < .0001), and VT (5.8% vs 8.5%, P=.02) rates were significantly lower in the flecainide group for population 1. In population 2, adverse event rates were also lower, although not significantly, in the flecainide compared to the class-3 AAD group for mortality (20.9% vs 25.8%, P=.26), HF hospitalization (24.5% vs 26.1%, P=.73), VT (10.9% vs 14.7%, P=.28) and MACE (44.5% vs 49.5%, P=.32). Flecainide in select patients with stable CAD for AF has a favorable safety profile compared to class-3 AADs. These data suggest the need for prospective trials of flecainide in AF patients with CAD to determine if the current guideline-recommended exclusion is warranted.

Comparison of dronedarone vs. flecainide in the maintenance of sinus rhythm, following electrocardioversion in adults with persistent atrial fibrillation: a systematic review and meta-analysis.

To compare flecainide and dronedarone for sinus rhythm (SR) maintenance following electrocardioversion of persistent atrial fibrillation (AF), in patients with minimal or no structural heart disease. A systematic search of publications using EMBASE, CENTRAL, CINAHL, and MEDLINE (1989-2019), identified a total of 595 articles. No limitations were applied. Nine articles met the inclusion criteria [five randomized controlled trials (RCTs) and four cohort studies], encompassing 1349 persistent AF candidates. Two retrospective studies compared flecainide with dronedarone, indicating a 6% reduced risk of AF recurrence with flecainide; however, results were not statistically significant [risk ratio (RR) 0.94, 95% confidence interval (CI) 0.71-1.24; P = 0.66]. One RCT compared dronedarone to placebo, demonstrating a 28% reduced risk of AF recurrence at 6 months (RR 0.72, 95% CI 0.58-0.90; P = 0.004). Two RCTs compare flecainide to placebo, when a 16% decreased risk of AF recurrence at 6-12 months was indicated; however, these results were not statistically significant (RR 0.84, 95% CI 0.66-1.07; P = 0.16). Within a 6- to 12-month follow-up period, a combined recurrence rate of AF was examined, in which flecainide and dronedarone maintained SR in 50% and 42%, respectively. Four articles satisfied quality appraisal, one of which focused on flecainide data. Dronedarone and flecainide displayed similar efficacy in maintaining SR in patients following electrocardioversion for persistent AF. The SR maintenance was numerically but not statistically significant in the flecainide group. Side effects uncovered similar pro-arrhythmic activity. However, in light of the deficiency of volume and quality of available evidence, the writer acknowledges the requirement for future research.

PO165 Simple Indices of Infarct Size Post ST-Elevation Myocardial Infarction (STEMI) Provides Similar Risk Stratification to Cardiac MRI

Class 1C antiarrhythmic drugs (AAD) have been associated with harm in patients treated for ventricular arrhythmias with a prior myocardial infarction. Consensus guidelines have advocated that these drugs not be used in patients with stable coronary artery disease (CAD). However, long-term data are lacking to know if unique risks exist when these drugs are used for atrial fibrillation (AF) in patients with CAD without a prior myocardial infarction.In 24,315 patients treated with the initiation of AADs, two populations were evaluated: (1) propensity-matched AF patients with CAD were created based upon AAD class (flecainide, n = 1,114, vs class-3 AAD, n = 1,114) and (2) AF patients who had undergone a percutaneous coronary intervention or coronary artery bypass graft (flecainide, n = 150, and class-3 AAD, n = 1,453). Outcomes at 3 years for mortality, heart failure (HF) hospitalization, ventricular tachycardia (VT), and MACE were compared between the groups.At 3 years, mortality (9.1% vs 19.3%, P < .0001), HF hospitalization (12.5% vs 18.3%, P < .0001), MACE (22.9% vs 36.6%, P < .0001), and VT (5.8% vs 8.5%, P = .02) rates were significantly lower in the flecainide group for population 1. In population 2, adverse event rates were also lower, although not significantly, in the flecainide compared to the class-3 AAD group for mortality (20.9% vs 25.8%, P = .26), HF hospitalization (24.5% vs 26.1%, P = .73), VT (10.9% vs 14.7%, P = .28) and MACE (44.5% vs 49.5%, P = .32).Flecainide in select patients with stable CAD for AF has a favorable safety profile compared to class-3 AADs. These data suggest the need for prospective trials of flecainide in AF patients with CAD to determine if the current guideline-recommended exclusion is warranted.

First-Line Antiarrhythmic Transplacental Treatment for Fetal Tachyarrhythmia: A Systematic Review and Meta-Analysis.

BackgroundThere is no consensus on the most effective and best tolerated first‐line antiarrhythmic treatment for fetal tachyarrhythmia. The purpose of this systematic review and meta‐analysis was to compare the efficacy, safety, and fetal–maternal tolerance of first‐line monotherapies for fetal supraventricular tachycardia and atrial flutter.Methods and ResultsA comprehensive search of several databases was conducted through January 2017. Only studies that made a direct comparison between first‐line treatments of fetal tachyarrhythmia were included. Outcomes of interest were termination of fetal tachyarrhythmia, fetal demise, and maternal complications. Ten studies met inclusion criteria, with 537 patients. Overall, 291 patients were treated with digoxin, 137 with flecainide, 102 with sotalol, and 7 with amiodarone. Digoxin achieved a lower rate of supraventricular tachycardia termination compared with flecainide (odds ratio [OR]: 0.773; 95% confidence interval [CI], 0.605–0.987; I2=34%). In fetuses with hydrops fetalis, digoxin had lower rates of tachycardia termination compared with flecainide (OR: 0.412; 95% CI, 0.268–0.632; I2=0%). There was no significant difference in the incidence of maternal side effects between digoxin and flecainide groups (OR: 1.134; 95% CI, 0.129–9.935; I2=80.79%). The incidence of maternal side effects was higher in patients treated with digoxin compared with sotalol (OR: 3.148; 95% CI, 1.468–6.751; I2=0%). There was no difference in fetal demise between flecainide and digoxin (OR: 0.767; 95% CI, 0.140–4.197; I2=44%).ConclusionsFlecainide may be more effective treatment than digoxin as a first‐line treatment for fetal supraventricular tachycardia.

Flecainide in Amyotrophic Lateral Sclerosis as a Neuroprotective Strategy (FANS): A Randomized Placebo-Controlled Trial

BackgroundAbnormalities in membrane excitability and Na+ channel function are characteristic of amyotrophic lateral sclerosis (ALS). We aimed to examine the neuroprotective potential, safety and tolerability of the Na+ channel blocker and membrane stabiliser flecainide in ALS. MethodsA double-blind, placebo-controlled, randomised clinical trial of flecainide (200mg/day) for 32-weeks with a 12-week lead-in phase was conducted in participants with probable or definite ALS recruited from multiple Australian centres (ANZCT Registry number ACTRN12608000338369). Patients were reviewed by a cardiologist to rule out cardiac contraindications. Participants were randomly assigned (1:1) to flecainide or placebo using stratified permuted blocks by a central pharmacy. The primary outcome measure was the slope of decline of the ALS Functional Rating Scale-revised (ALS FRS-r) during the treatment period. FindingsBetween March 11, 2008 and July 1, 2010, 67 patients were screened, 54 of whom were randomly assigned to receive flecainide (26 patients) or placebo (28 patients). Four patients in the flecainide group and three patients in the placebo group withdrew from the study. One patient in the flecainide group died during the study, attributed to disease progression. Flecainide was generally well tolerated, with no serious adverse events reported in either group. There was no significant difference in the rate of decline in the primary outcome measure ALS-FRS-r between placebo and flecainide treated patients (Flecainide 0.65 [95% CI 0.49 to 0.98]; Placebo 0.81 [0.49 to 2.12] P=0.50). However, the rate of decline of the neurophysiological index was significantly reduced in the flecainide group (Flecainide 0.06 [0.01 to 0.11]; Placebo 0.14 [0.09 to 0.19], P=0.02). Placebo-treated patients demonstrated greater CMAP amplitude reduction during the course of the study in the subset of patients with a reduced baseline CMAP amplitude (Flecainide: −15±12%; Placebo −59±12%; P=0.03). Flecainide-treated patients maintained stabilized peripheral axonal excitability over the study compared to placebo. InterpretationThis pilot study indicated that flecainide was safe and potentially biologically effective in ALS. There was evidence that flecainide stabilized peripheral axonal membrane function in ALS. While the study was not powered to detect evidence of benefit of flecainide on ALS-FRS-r decline, further studies may demonstrate clinical efficacy of flecainide in ALS.

Vernakalant: Perception of state of health in patients with a recent-onset atrial fibrillation

Vernakalant is a new, safe and effective drug used intravenously, which has proved to be more rapid in converting recent onset atrial fibrillation (AF) to sinus rhythm compared to placebo, amiodarone, propafenone, and flecainide in clinical studies. Until now no study has been conducted comparing the perception of state of health in patients who received vernakalant versus propafenone or flecainide for conversion of recent-onset AF. The aim of our study is to compare the change of perception of state of health from screening to hour 2 in patients treated with vernakalant and propafenone or flecainide for conversion of recent-onset AF. Eighty hemodynamically stable patients with recent onset AF without structural heart disease were prospectively included. A single oral dose of propafenone 600 mg was administered to 30 patients, 30 patients received intravenous vernakalant and the remaining 20 patients received a single oral dose of flecainide 300 mg. Clinical, laboratory variables and perception of state of health from screening to hour 2 treated with these drugs measured by the EQ-5 D quality-of-life assessments visual analog scale were recorded. Baseline characteristics were similar in the three groups. Treatment with vernakalant resulted in a significantly greater improvement in patient perception of state of health at hour 2 compared with propafenone and flecainide. In the vernakalant group, a mean increase (from baseline) of 12.1 points was seen compared with a mean increase of 5.4 points in the propafenone group or 5.2 points in flecainide group (p < 0.01). The change of perception of state of health from screening to hour 2 treated with vernakalant had a significantly statistical improvement compared with propafenone or flecainide for conversion recent-onset AF.

Three-month lower-dose flecainide after catheter ablation of atrial fibrillation

Atrial tachyarrhythmias (AT) commonly recur within the first 3 months after radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF), and the influence of antiarrhythmic drugs (AADs) on the recurrences has not been fully elucidated. We sought to evaluate the efficacy of a 3-month lower-dose flecainide regime on early and late recurrences of ATs. We randomly assigned 126 patients, who underwent RFCA for AF, to the flecainide group (150 or 100 mg/day according to their body weight) or to the control group receiving no AADs. The primary endpoint was any AT lasting for ≥30 s during the first 3 months and the secondary endpoint was a composite of ATs lasting for ≥24 h or requiring cardioversion or hospitalization during the same period. All AADs were stopped after the first 3 months and the late arrhythmia recurrences were also evaluated. The primary endpoint rates were 37 and 41% in the flecainide (143 ± 19 mg/day) and control groups, respectively (log-rank P = 0.76), and those of the secondary endpoint were 10 and 14%, respectively (log-rank P = 0.45). The estimated rates of maintaining sinus rhythm at 12 months after the first 3 months were 78 and 72%, in the flecainide and control groups, respectively (log-rank P = 0.68), and the rates were 51 and 90% in those with and without the primary endpoint, respectively (log-rank P < 0.001). The 3-month lower-dose flecainide therapy after AF ablation did not reduce the early and late arrhythmia recurrences. The clinically significant ATs were also not prevented.

Conversion of Recent-Onset Atrial Fibrillation: Which Drug is the Best?

Introduction: Vernakalant is a new, safe and effective drug used intravenously. It has proven to be more rapid in converting recent onset atrial fibrillation (AF) to sinus rhythm compared to placebo, amiodarone, propafenone and flecainide in clinical studies with few patients. At present no study has been conducted comparing these three drugs with a more substantial number of patients. The aim of our study is to compare the time to conversion to sinus rhythm, hospital stay and adverse events between vernakalant versus flecainide and propafenone in patients with a recent-onset AF. Materials and Methods: 150 hemodynamically stable patients with recent onset AF without structural heart disease were prospectively included. A single oral dose of propafenone 600 mg was administered to 50 patients; 50 patients received intravenous vernakalant; and 50 patients received a single oral dose of flecainide 300 mg. Clinical and laboratory variables were recorded. Results: Baseline characteristics were similar in the three groups.Time to conversion to sinus rhythm was 12 minutes in the vernakalant group versus 151 minutes in the propafenone group and 162 minutes in flecainide group (p< 0.01) The hospital stay was 243 minutes in the vernakalant group versus 422 minutes in the propafenone group and 410 minutes in flecainide group (p<0.01) (Figure 2). No adverse events were reported. Conclusion: The time to conversion to sinus rhythm and hospital stay were statistically shorter in vernakalant group compared to flecainide and to propafenone. There were no adverse events in the three groups.

Flecainide versus vernakalant for conversion of recent-onset atrial fibrillation

An oral single dose of flecainide is used worldwide for conversion of recent onset atrial fibrillation (AF) in hemodynamically stable patients without structural heart disease. Vernakalant is a novel, rapid drug, which is used intravenously, with proven effectiveness and safety compared to placebo and amiodarone in randomized clinical trials. The aim of our study was to compare the time taken for conversion of recent onset AF in patients treated with vernakalant or flecainide. This is a sequential study in which 32 hemodynamically stable patients with recent onset AF without structural heart disease were prospectively and consecutively included in two periods, one for each drug. A single oral dose of flecainide 300 mg was administered to 15 patients and 17 patients received intravenous vernakalant. Clinical and laboratory variables, conversion rate and time to conversion were recorded. Baseline characteristics were similar in both groups. Time to conversion to sinus rhythm was of 163 min (120-300) in the flecainide group versus 10 min (6-18) in the vernakalant group (p=0.0001). Time to conversion of AF to sinus rhythm was significantly shorter in the vernakalant group compared with the flecainide group, and was associated with shorter hospital stay. This reduction in hospital stay length may produce benefits in patients' medical care, costs and welfare.

Flecainide versus Electrical Cardio Version in Patients with a Recent-Onset Atrial Fibrillation

Introduction: Flecainide is a Class IA drug according the European Guidelines for conversion of recent-onset atrial fibrillation in patients without structural heart disease. Electrical Cardio version is the first line in many centers in all over the world in this population. Up to the present no study has been conducted comparing Flecainide with Electrical Cardio version (EC) for conversion of recent-onset atrial fibrillation. The goal of our study was to compare the conversion rate of recent-onset AF, hospital stay length and adverse events in hemodynamically stable patients without structural heart disease treated with flecainide or EC. Methods: 50 hemodynamically stable patients with recent onset AF without structural heart disease were included. 30 patients received oral loading dose of flecainide 300 mg and other 20 patients EC. Clinical and laboratory variables were recorded. Results: Baseline characteristics were similar in both groups. The conversion rate was 70% in the flecainide group and 100 % in the EC group (p<0.01). Hospital stay length was 432 minutes and 263 minutes in EC (p<0.05).There were no adverse events in both groups. Conclusion: The conversion rate of recent-onset AF was lower and hospital stay length was shorter in EC group compared with flecainide group with significantly statistical differences. In both groups were no adverse events.

Relationship between subjective symptoms and trans-telephonic ECG findings in patients with symptomatic paroxysmal atrial fibrillation and flutter

In patients with paroxysmal atrial fibrillation or flutter (PAF/PAFL), subjective symptoms are not concordant with real arrhythmic events. It is important to elucidate the incidence of asymptomatic PAF/PAFL in symptomatic patients in a clinical setting. To identify a possible relationship with subjective symptoms, we reviewed 6319 trans-telephonic electrocardiographic strips (ECGs) recorded from 123 patients in a double-blind, placebo-controlled trial examining dose-response effects of flecainide. During a 4-week observation, 2848 ECGs, comprising 894 (31.4%) symptomatic and 1954 (68.6%) asymptomatic tracings, and, during 31 days of treatment, 3471 ECGs, comprising 874 (25.2%) symptomatic and 2587 (74.8%) asymptomatic tracings, were transmitted. There were significantly fewer symptomatic ECGs during the treatment period (Fisher's exact test, P<0.01). Asymptomatic episodes accounted for 23.5% of the total in the observation period and 22.4% of that in the treatment period (Fisher's exact test, P=0.561). But the frequency of asymptomatic PAF/PAFL dropped significantly, from 11.1% to 3.9% (P<0.01), in the group receiving flecainide 200 mg/day. In the observation period, the positive predictive value of subjective symptoms was about 50%, and the sensitivity in predicting PAF/PAFL, around 80%. During treatment, these values did not change significantly, but negative predictive value (NPV) and specificity increased in the 200 mg flecainide group. In the analysis of each case, significant dose-response profiles were found in NPV (P=0.019) and specificity (P=0.041). Asymptomatic PAF/PAFL was not rare in symptomatic patients, and flecainide reduced both symptomatic and asymptomatic episodes.

Comparison of intravenous flecainide, propafenone, and amiodarone for conversion of acute atrial fibrillation to sinus rhythm

In a prospective, single-blind trial, we randomized 150 consecutive symptomatic patients with acute (≤48 hours’ duration) atrial fibrillation to receive intravenous flecainide, propafenone, or amiodarone. Flecainide and propafenone were administered as a bolus dose of 2 mg/kg in 20 minutes. A second bolus dose of 1 mg/kg in 20 minutes was administered if conversion to sinus rhythm was not achieved after 8 hours. Amiodarone was administered as a bolus of 5 mg/kg in 20 minutes followed by a continuous infusion of 50 mg/hour. By the end of a 12-hour observation period, conversion to sinus rhythm was achieved in 45 patients (90%) in the flecainide group, 36 (72%) in the propafenone group, and 32 (64%) in the amiodarone group (p = 0.008 for the overall comparison, p = 0.002 for flecainide vs amiodarone, p = 0.022 for flecainide vs propafenone, and p = 0.39 for propafenone vs amiodarone). When compared with amiodarone, this higher reversion rate with flecainide was present from the first hour of the study period. However, only after administering the second bolus was there a significant difference between flecainide and propafenone. Median time to conversion to sinus rhythm was different among groups (p <0.001), and it was lower in the flecainide (25 minutes; range 4 to 660) and propafenone (30 minutes; range 10 to 660) groups than in the amiodarone group (333 minutes; range 15 to 710; p <0.001 for both comparisons). Flecainide, at the doses administered in this study, is more effective than propafenone and amiodarone for conversion of acute atrial fibrillation to sinus rhythm. Propafenone and amiodarone have similar conversion rates, although propafenone was faster in achieving the conversion to sinus rhythm.

The actions of ibutilide and class Ic drugs on the slow sodium channel: new insights regarding individual pharmacologic effects elucidated through combination therapies.

Ibutilide (I) has been reported to block I(k) and to delay inactivation of the slow Na(+) current (S-Na). There is debate about the clinical importance of the latter. Class Ic drugs block the fast Na(+) channel, but their effect on S-Na is uncertain. If Ic treatment before infusion lessened the QT increase with I, this result would suggest both an Ic effect on S-Na and significant S-Na actions of I. We infused I, 2 mg over 30 minutes, to 6 patients pretreated with propafenone (n = 5) or flecainide (n = 1) (group 1) and compared their increase with the QT increase seen with I alone in a combined group of 85 patients from our lab and the multicenter I database (group 2). The QTc increased in group 2, 65 ms, from 413 to 478 ms. This effect was attenuated by 47% in group 1 patients to 34 ms (P <.01). There appeared to be a dose-response relationship between Ic dose and its effects on QTc prolongation. The lowest dose of propafenone had minimal effect on the increase in QTc with I (72 ms), while higher doses of propafenone and high doses of flecainide attenuated the increase to 13 to 39 ms. Nonetheless, ibutilide efficacy was not changed, possibly suggesting differing importance of K(+) channel and slow sodium-channel effects in atrial versus ventricular tissues, and having implications for means to reduce some antiarrhythmic drug proarrhythmia without reducing efficacy. (1) Pretreatment with Ic agents can reduce the increase in QTc seen with I; (2) I's effect in humans appears to be at least partly mediated through the delay of S-Na inactivation; and (3) Ic agents probably inhibit S-Na.

Double‐Blind Comparison of Cibenzoline Versus Flecainide in the Prevention of Recurrence of Atrial Tachyarrhythmias in 139 Patients

Background: The efficacy and safety of antiarrhythmic drugs for the prevention of atrial arrythmias are controversial because previous studies were nonrandomized or involved nonselected patients. The aim of this study was to evaluate the efficacy and tolerance of two Class I antiarrythmic drugs, cibenzoline, and flecainide, for the treatment of atrial arrhythmias in carefully selected patients.Patients and Methods: One hundred thirty‐nine patients suffering from documented atrial arrhythmias (mean age 63 ± 12 years, 80 males, 59 females) were enrolled in randomized, double‐blind, parallel clinical trials. Seventy patients received cibenzoline and 69 received flecainide; they were followed for a period of 6 months. All patients had good systolic ventricular function. The recurrence of atrial arrhythmias was diagnosed on symptoms, resting ECG, and 24‐hour ambulatory ECG 3 and 6 months after commencing treatment.Results: Twenty‐seven patients were withdrawn during the study, 13 for adverse side effects, 4 for proarrhythmic effects, and 3 for medical events; 7 were lost to follow‐up. Forty‐three patients had one recurrence of atrial arrhythmias (23 in the cibenzoline group, 20 in the flecainide group). The cumulative percentage of patients free from recurrence was not significantly different in either group at 6 months (63.7% in the cibenzoline group and 66.8% in the flecainide group). Cardiac adverse side effects were more frequent with flecainide than cibenzoline (5 vs. 2). One atrial proarrhythmic effect was observed.Conclusion: Cibenzoline and flecainide are both Class I antiarrhythmic agents which are well tolerated and may be safely administered to prevent alrial arrhythmias. A.N.E. 1999;4(1):53–59

Divergent effect of acute ventricular dilatation on the electrophysiologic characteristics of d,l-sotalol and flecainide in the isolated rabbit heart.

The interaction between acute ventricular dilatation (AVD) as one aspect of ventricular dysfunction and Class I and III antiarrhythmic drugs is uncertain. We therefore investigated the effects of AVD on the electrophysiologic properties of d,l-sotalol and flecainide. The isolated rabbit heart was used as a model of AVD. The ventricular size and, therefore, the diastolic pressure were modified by sudden volume changes of a fluid-filled balloon placed in the left ventricle. Pacing was performed alternately using epi- and endocardial monophasic action potential (MAP)-pacing catheters at cycle lengths from 1,000 to 300 msec. d,l-Sotalol (10 microM) resulted in a significant (P < 0.05) lengthening of refractoriness (+13.5% +/- 3.1%), MAP duration (+14.9% +/- 3.2%), and QT interval (+15.5% +/- 4.1%) (mean +/- SEM at 1,000 msec). These effects had a reverse rate-dependence. AVD to a diastolic pressure of 30 mmHg reduced refractoriness and left ventricular MAP duration. In comparison with the control group with the same extent of AVD, d,l-sotalol still led to a significant prolongation of repolarization for all cycle lengths except 300 msec, so that its effects were not absolutely but relatively preserved. In contrast, flecainide (2 microM) had no significant effects on refractoriness or MAP duration. It led to a significant, rate-dependent increase of pacing thresholds (+47.6% +/- 8.2%), prolongation of QRS (+48.8% +/- 5.6%), and conduction time (+78.6% +/- 8.6%) (mean +/- SEM at 300 msec). In the flecainide group, AVD significantly increased the normal rate-dependent prolongation of QRS (+16.7% +/- 5.5%) and conduction time (+17.1% +/- 4.3%). Our data demonstrate that, during AVD, the Class III effect of d,l-sotalol is preserved, whereas flecainide's effect of slowing conduction is exaggerated. This may contribute to flecainide-related proarrhythmia in certain clinical situations.

Comparison of the safety and efficacy of flecamide versus propafenone in hospital out-patients with symptomatic paroxysmal atrial fibrillation/flutter

To assess the cardiac and extracardiac safety and efficacy of flecainide versus propafenone in patients suffering from episodes of paroxysmal atrial fibrillation (AF) or atrial flutter, 97 patients were enrolled in a randomized, open-label, long-term, parallel, comparative multicenter study. The diagnosis of paroxysmal AF or atrial flutter had to be fully documented prior to inclusion in the study. Of the 97 patients enrolled in the study, 48 patients (25 men, 23 women, mean age 62.4 ± 12.3 years) received flecainide; 49 patients (26 men, 23 women, mean age 63.6 ± 12.2 years) received propafenone. The initial dose of f lecainide was 50 mg twice daily, and this could be increased in steps of 50 mg twice daily every 4 days to a maximum of 300 mg/day. The initial dose of propafenone was 300 mg twice daily and this could be increased in steps of 300 mg every 4 days to a maximum of 1200 mg/day. At each visit, medical events, vital sign measurements (blood pressure, pulse rate), concomitant medications, adverse experiences, and study drug dosage changes were evaluated. Routine clinical laboratory tests were evaluated at the month 6 visit, and a 24-hr Holter recording was obtained at the month 1 visit. Almost half (45) of the patients were discontinued from the study before completing 1 year of therapy. The probability of successful treatment versus time—i.e., the proportion of patients who remained on therapy over the course of 1 year therapy—was 0.619 for the flecainide group and 0.469 for the propafenone group (p = 0.079; difference not significant). The difference is largely attributed to the higher proportion of patients in the propafenone group (9) than in the flecainide group (2) who experienced side effects important enough to stop the treatment. (The incidence of side effects was not statistically different between treatment groups, although it was higher in the propafenone group.) The proportion of patients who discontinued treatment due to inadequate response was similar in the 2 groups: 11 patients (22.9%) in the flecainide group and 12 patients (24.4%) in the propafenone group withdrew from the study, primarily because of an inadequate response, i.e., they experienced an increase in duration, frequency, and severity of attacks of AF or atrial flutter. Neurologic signs, central and peripheral, were mostly encountered in the flecainide group (8.5%), and, gastrointestinal effects were more often reported in the propafenone group (16.7%). In paroxysmal AF and paroxysmal atrial flutter, flecainide and propafenone are equally effective. However, in this study the probability of a patient's staying on flecainide after 1 year had a tendency to be higher than the probability of staying on propafenone, due to a greater proportion of secondary effects with propafenone.

A randomized comparison of flecainide versus verapamil in paroxysmal supraventricular tachycardia

Reentrant paroxysmal supraventricular tachycardias (PSVT) are frequently encountered in clinical practice. Verapamil and flecainide have both been successfully used as chronic oral therapy to prevent PSVT recurrences. This open-label, randomized, multicenter study was designed to compare the efficacy and adverse effects of verapamil (median dose, 240 mg/day) versus flecainide (median dose, 200 mg/day) in patients with frequent and symptomatic attacks of PSVT (other than atrial fibrillation or flutter). A total of 121 patients receiving flecainide (n = 63) or verapamil (n = 58) were followed for 8.1 ±5.1 and 7.5 ± 5.4 months, respectively. Response was judged clinically as effective or not by the treating physician. By life table analysis, 11% discontinued flecainide and 19% discontinued verapamil for inefficacy at 1 year (difference not significant). Both groups showed a marked reduction in the frequency of attacks of PSVT. Before therapy, 71% of flecainide patients and 73% of verapamil patients had ≥2 attacks per month. During therapy, 86% of all flecainide patient-months and 73% of all verapamil patient-months occurred with 0 or 1 attack; 19 (30%) patients on flecainide completed the trial (>270 days) without symptomatic attacks versus 7 (13%) of the patients on verapamil (p = 0.026). Both drugs were well tolerated; 19% of the flecainide group discontinued primarily because of adverse effects, compared with 24% discontinuing verapamil for this reason (difference not significant). Both flecainide and verapamil are effective and well tolerated for the prevention of recurrences of PSVT. For patients in whom radiofrequency ablation procedures cannot be performed or are not indicated, either therapy is a reasonable choice for long-term prophylaxis.

Predicting mortality after myocardial infarction from the response of RR variability to antiarrhythmic drug therapy

Objectives. This study was designed to test the hypothesis that antiarrhythmic drugs that decrease RR variability will predict all-cause mortality during follow-up after myocardial infarction.Background. RR variability, a noninvasive indicator of autonomic nervous system activity, predicts death after acute myocardial infarction independently of other risk predictors and changes substantially in response to some drugs. A previous study in patients with chronic heart disease and frequent ventricular premature complexes reported that flecainide decreased vagal modulation of RR intervals but amiodarone did not. The investigators of that study speculated that changes in RR variability during antiarrhythmic drug therapy predict an increased mortality rate during long-term drug treatment. To explore this hypothesis further, we compared the effects of encainide and flecainide, which increase long-term mortality substantially, on RR variability with the effects of placebo and moricizine, which have no significant effect on mortality during long-term treatment of unsustained ventricular arrhythmias after myocardial infarction.Methods. The 24-h power spectral density was computed from the baseline electrocardiography recordings and drug evaluation tapes, and six frequency domain measures of RR variability were calculated: ultra-low frequency (<0.0033 Hz), very low frequency (0.0033 to <0.04 Hz), low frequency (0.04 to <0.15 Hz) and high frequency power (0.15 to <0.40 Hz), plus total power (<0.40 Hz) and the ratio of low to high frequency power. Changes in power spectral measures were related to drug treatment and to mortality.Results. In the placebo group, values for RR interval and RR variability increased because of recovery from the effects of acute myocardial infarction. Contrasting placebo treatment with all three active antiarrhythmic drug treatments taken together showed that of all the measures of RR variability, only NN50, pNNSO and low frequency power changed significantly during drug treatment (Bonferroni adjusted p value <0.025); these variables all decreased during drug therapy. Contrasting encainide and flecainide with moricizine, we found that the encainide and flecainide groups taken together showed a larger decrease in dLF than moricizine, but the difference was of borderline significance (Bonferroni adjusted p value <0.08). Survival was significantly worse in the groups treated with encainide and flecainide than in the groups treated with placebo or moricizine (relative risk >2.0, adjusted p < 0.05). The antiarrhythmic drug-induced change in measures of RR variability was not a significant predictor of all-cause mortality during a year of follow-up after myocardial infarction.Conclusions. Encainide, flecainide and moricizine all caused a decrease in RR variability in patients studied ~1 month after acute myocardial infarction. Encainide and flecainide caused a significant increase in mortality rates; placebo and moricizine did not. Baseline measurements of RR variability also predicted all-cause mortality after myocardial infarction. The decrease in RR variability produced by the three antiarrhythmic drugs did not predict mortality during follow-up.