Propafenone Group Research Articles

Effects of oral propafenone administration before electrical cardioversion of chronic atrial fibrillation: A placebo-controlled study

Objectives. Our aim was to evaluate the benefits and risks of administering propafenone before electrical defibrillation for chronic atrial fibrillation.Background. In this context, an antiarrhythmic drug—although potentially useful in preventing early recurrence of arrhythmia—could adversely affect the defibrillation threshold and reduce the cardioversion success rate.Methods. We randomly assigned 100 patients with chronic atrial fibrillaton to oral treatment with either placebo (51 patients) or 750 mg/day of propafenone (49 patients) for 48 h before administration of direct current shock. After successful cardioversion, all patients received propafenone therapy and were followed up for 48 h.Results. Before defibrillation, three patients in the propafenone group (6.1%) had reversion to sinus rhythm and one had sustained ventricular tachycardia. Shock efficacy (82.4% vs. 84.4%) and the cumulative effective energy (395 ± 258 vs. 421 ± 236 J) were not different between the placebo and propafenone groups. In the propafenone group, 11 patients had their arrhythmia transformed into atrial flutter and required a lower energy level for arrhythmia conversion than did the other patients with continued atrial fibrillation (245 ± 197 vs. 493 ± 215 J, p < 0.01); the latter patients showed a trend (p < 0.10) toward higher energy requirements than that of patients who received placebo. The incidence of asymptomatic bradyarrhythmias was higher in the propafenone group (28.9% vs. 7.1%, p < 0.02), but more patients who received placebo had early recurrence of atrial fibrillation (16.7% vs. 0%, p < 0.02). Two days after cardioversion, more patients given propafenone (73.5% vs. 52.9%, p < 0.05) were discharged from the hospital with sinus rhythm. During the in-hospital stay, propafenone was withdrawn from six patients (6.6%) because of side effects.Conclusions. Propafenone, given before electrical cardioversion for chronic atrial fibrillation does not affect the mean defibrillation threshold or the rate of successful arrhythmia conversion. It decreases the recurrence of atrial fibrillation early after shock, thus allowing more patients to be discharged from the hospital with sinus rhythm.

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 Randomised Study Comparing Digoxin and Propafenone in the Treatment of Recent Onset Atrial Fibrillation

The aim of this study was to compare the efficacy and safety of propafenone (2 mg/kg intravenously over 10 minutes) and digoxin (0.007 mg/kg intravenously over 10 minutes) in the conversion of recent onset <72 hours) atrial fibrillation to sinus rhythm. A consecutive series of 50 uncomplicated patients (no contraindications to either drug and without clinical heart failure) was randomly divided into 2 groups of 25 patients each. The 2 groups were similar in age, gender, concomitant diseases, previous paroxysmal atrial fibrillation, duration of the arrhythmia, electrocardiographic parameters, basal blood pressure and 2D-echocardiographic profile. Sinus rhythm was restored in a higher percentage of propafenone-treated patients [22 of 25 patients (88%) vs 8 of 25 (32%); p = 0.00005] and within a shorter time period (mean 22 vs 96 minutes; p = 0.0004) relative to digoxin-treated patients. The study design allowed for conditional crossover of patients who did not respond to initial drug treatment. 11 of 17 patients who did not respond to digoxin were treated with propafenone; conversion to sinus rhythm was achieved in 6 of 11 (54%) patients within 3 hours. No clinically relevant adverse effects were noted in either treatment group. Neither treatment gave rise to any significant modification in QRS- or QTc-interval morphology. In the propafenone group, normal left atrium measurement values (anteroposterior diameter, longitudinal diameter, transversal diameter and a preserved ejection fraction) were considered predictive factors for conversion to sinus rhythm. Additionally, the high percentage of early conversions obtained with propafenone allowed earlier discharges in this group of patients compared with that of digoxin. In conclusion, propafenone was well tolerated and was more effective than digoxin in the treatment of patients with recent onset atrial fibrillation. The drug offered advantages over digoxin with respect to its rapid onset of action and reduction in the number of patients who required hospitalisation.

Comparison of propafenone to atenolol for the prophylaxis of postcardiotomy supraventricular tachyarrhythmias: a prospective trial

To compare the efficacy of propafenone to atenolol in the prevention of supraventricular tachyarrhythmias (SVT) following cardiac surgery, 207 consecutive patients were randomly allocated to receive either propafenone 300 mg twice daily (105 patients) or atenolol 50 mg once daily (102 patients) orally for 7 days after operation. Double blinding was achieved using placebos. The end point was the development of a SVT which was symptomatic, recurrent, or lasting over 2 minutes, or the occurrence of adverse effects possibly attributable to the drugs. The groups were well matched for age, sex, bypass- and cross-clamp times, and other data. Thirteen patients in the propafenone group and 11 in the atenolol group developed SVT during the first week after operation. (P = 0.89, non significant, chi-squared with Yates' correction). In our study propafenone and atenolol were of approximately equal efficacy in preventing post cardiotomy SVT. Propafenone may have an advantage in being less negatively inotropic than atenolol; it could therefore be used in patients with poor left ventricular function or marginal haemodynamics when a beta blocker is contraindicated.

Clinical Course of Recent-Onset Atrial Fibrillation Treated With Oral Propafenone

Atrial fibrillation (AF) is one of the most common cardiac arrhythmias in the adult population. Propafenone is a class 1c antiarrhythmic agent that has an electrophysiologic profile suggesting that it might be potentially effective in recent-onset AF. The present study was undertaken, therefore, to examine the time course as well as the frequency of successful conversion in patients with recent-onset AF treated with propafenone administered orally. Fifty patients with recent-onset AF were recruited into 2 groups: 25 patients were given propafenone, 150 mg every 4 h, and 25 patients served as a control group and received verapamil (a drug known to slow the ventricular response but not to restore sinus rhythm) 40 mg, every 4 h and up to 48 h or until conversion to sinus rhythm occurred. Of the 50 patients, 2 refused to continue the study and another 2 were excluded because of left heart failure. Conversion to sinus rhythm occurred in 21 of 24 patients (87 percent) in the propafenone group as compared with 9 of 22 (41 percent) in the verapamil group (p < 0.001). In 10 patients in the propafenone group, conversion occurred within 12 h, within 24 h in another 9 patients, and between 24 and 48 h in the remaining 2 patients. There was no correlation between the duration of AF prior to entry into the study and the subsequent incidence of and time to conversion with propafenone. With respect to cause of AF, all groups showed a high incidence of conversion. Two patients developed heart failure during treatment and one patient (in the verapamil group) developed embolic stroke while still having atrial fibrillation. We conclude that in patients with AF, the prognosis for conversion to sinus rhythm within 48 h, with propafenone, is excellent (87 percent) and safe.

Implantable cardioverter defibrillator compared with antiarrhythmic drug treatment in cardiac arrest survivors (the Cardiac Arrest Study Hamburg)

In 1987, the Cardiac Arrest Study Hamburg (CASH), a prospective, multicenter, randomized controlled study, was started in survivors of sudden cardiac death resulting from documented ventricular tachyarrhythmias. Through December 1991, 230 survivors (46 women, 184 men; mean age 57 ± 11 years) of cardiac arrest caused by ventricular tachyarrhythmias were randomly assigned to receive either oral propafenone (56 patients), amiodarone (56 patients), or metoprolol (59 patients) or to have an implantable defibrillator (59 patients) without concomitant antiarrhythmic drugs. The primary endpoint of the study was total mortality. In March 1992, the propafenone arm of CASH was stopped because of excess mortality compared with the implantable defibrillator group. This article presents preliminary results of the comparison of implantable defibrillator therapy with propafenone therapy. A significantly higher incidence of total mortality, sudden death (12%), and cardiac arrest recurrence or sudden death (23%) was found in the propafenone group compared with the implantable defibrillator-treated patients (0%, p < 0.05). It was concluded that, in survivors of cardiac arrest, propafenone treatment is less effective than implantable defibrillator treatment.

Acute pharmacologic conversion of atrial fibrillation and flutter: The role of flecainide, propafenone, and verapamil

Efficacy and safety of intravenous flecainide (2 mg/kg body weight in 10 minutes), verapamil (10 mg in 1 minute), and propafenone (2 mg/kg body weight in 10 minutes) were investigated in 90 consecutive patients with atrial fibrillation (AF) or flutter (AFL). In the first 40 patients, flecainide and verapamil were evaluated; in the second 50 patients, flecainide and propafenone were compared, both in a single-blind randomized study design. The primary end point was sinus rhythm occurring within 1 hour after start of infusion. Sinus rhythm was attained in 32 of 37 patients (86%) with AF treated with flecainide and in 11 of 20 patients (55%) with AF treated with propafenone. In recent onset AF (≤24 hours) conversion rates were 24 of 25 patients (96%) in the flecainide group and 8 of 14 patients (57%) in the propafenone group (p < 0.05). Conversion of AFL occurred in only 1 of 8 patients (13%) in the flecainide-treated patients and in 2 of 5 patients (40%) treated with propafenone (difference not significant). Verapamil was almost ineffective, since only 1 of 20 patients (5%) responded within 1 hour. Time to conversion was 21 ± 17 minutes in the flecainide group and 16 ± 10 minutes in the propafenone group. QRS widening occurred in flecainide-treated patients (83 ± 15 to 99 ± 20 msec; p < 0.001), but not after propafenone (83 ± 11 to 86 ± 12 msec). Significantly higher plasma levels were found in patients with conversion within 1 hour using propafenone. Adverse reactions were more frequent in the flecainide group (31%) compared with the propafenone group (8%; p < 0.01). Conversion by class IC drugs may be preferable to direct current cardioversion or oral quinidine, usually requiring hospitalization.

Effects of Pentisomide and E-4031 on Canine Atrial Flutter Due to Reentry

Effects of new antiarrhythmic drugs, pentisomide [3.5 +/- 0.5 mg/kg intravenously (i.v.) n = 8], and E-4031 (5.6 +/- 1.0 micrograms/kg, n = 8), a class III drug, on atrial flutter (AF) caused by reentry were compared with those of disopyramide (1.6 +/- 0.2 mg/kg, n = 8) and propafenone (2.2 +/- 0.2 mg/kg, n = 8). AF was induced with burst atrial pacing after we made an intercaval crush in anesthetized, open-chest dogs. Termination of AF did not differ among test drugs (8 of 8 with disopyramide, 7 of 8 with propafenone, 6 of 8 with pentisomide, and 8 of 8 with E-4031). Cycle length (CL) of AF was prolonged more with propafenone (57 +/- 10%) and pentisomide (41 +/- 5%) than with E-4031 (12 +/- 3%, p less than 0.05). This was also true for increase in interatrial conduction time determined at a pacing CL of 150 ms. Increase in atrial effective refractory period (ERP) determined at a basic pacing CL of 300 ms did not differ among test drugs. Changes in CL of AF correlated significantly with those in interatrial conduction time (r = 0.84, p less than 0.001), but not with those of ERP (r = 0.10, NS). Reinitiation of AF was significantly greater in propafenone (7 of 7) and pentisomide (5 of 6) groups than in disopyramide (1 of 8) and E-4031 (0 of 8) groups (p less than 0.001). Pentisomide and E-4031 were effective in terminating canine AF due to reentry, as were disopyramide and propafenone. Reinitiation of AF was greater in dogs treated with antiarrhythmic drugs that had more prominent effects on conduction time than on ERP.

The value of class IC antiarrhythmic drugs for acute conversion of paroxysmal atrial fibrillation or flutter to sinus rhythm

In a single-blind randomized study, the efficacy and safety of intravenous propafenone (2 mg/kg body weight per 10 min) versus flecainidc (2 mg/kg per 10 min) were assessed in 50 patients with atrial fibrillation or flutter. Treatment was considered successful if sinus rhythm occurred within 1 h. Conversion to sinus was achieved in 11 (55%) of 20 patients with atrial fibrillation treated with propafenone and in 18 (90%) of 20 with atrial fibrillation treated with flecainide (p < 0.02). If atrial fibrillation was present ⩽24 h, conversion to sinus rhythm was achieved in 8 (57%) of 14 patients in the propafenone group and 13 (93%) of 14 in the flecainide group (p < 0.05). Atrial flutter was converted in two (40%) of five patients treated with propafenone and in one (20%) of five with flecainide (p = NS).Mean time to conversion was 16 ± 10 min in the propafenone group versus 18 ± 13 min in the flecainide group (p = NS). QRS lengthening (83 ± 15 to 99 ± 20 ms) was observed only in the patients treated with flecainide (p < 0.001). Patients successfully treated with propafenone showed significantly higher plasma levels than those whose arrhythmia did not convert to sinus rhythm. Transient adverse effects were more frequent in the flecainide group (40%) than in the propafenone group (8%) (p < 0.01).In conclusion, at a dose of 2 mg/kg in 10 min, flecainde is more effective than propafenone for conversion of paroxysmal atrial fibrillation to sinus rhythm. However, considering the propafenone plasma levels and very few adverse effects, the dose or infusion rate, or both, used in the propafenone group may not have been sufficient to achieve an optimal effect. Neither drug seems very effective in patients with atrial flutter.

Propafenone versus disopyramide: A double‐blind randomized crossover trial in patients presenting chronic ventricular arrhythmias

In vitro and in vivo electrophysiological studies have shown that propafenone could be classified as a class I antiarrhythmic agent. The aim of this study was to investigate the short-term antiarrhythmic efficacy and safety of propafenone in 10 patients compared to disopyramide in a double-blind randomized protocol. Included patients suffered from ventricular arrhythmias with at least 60 ventricular premature beats (VPB) per hour refractory to at least two other antiarrhythmic agents. At the end of the control period and of the two treatment periods during which patients received either propafenone (300 mg three times a day) or disopyramide (200 mg three times a day), clinical examination, Holter recordings, electrocardiogram, and clinical laboratory tests were performed. The PR interval and the QRS interval were significantly increased with propafenone, but not with disopyramide. The cQT interval was not significantly changed by either propafenone or disopyramide. Heart rate was decreased with propafenone (p less than 0.05) with no change in the diurnal/nocturnal circadian ratio variation. Heart rate was significantly decreased with disopyramide only during the day. Five of nine patients in the propafenone group and two of nine patients in the disopyramide group showed a reduction in ventricular premature beats greater than 80%. Total resolution of severe arrhythmias (repetitive events) was seen in 5 of 8 patients with propafenone; 2 of 8 with disopyramide. Adverse events, when they occurred, were mild (visual disturbances, epigastric discomfort, changes in taste perception, transient atrioventricular block with propafenone, and photophobia with disopyramide), and did not require reduction or discontinuation of study drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmogenic effects of antiarrhythmic drugs in patients with an old myocardial infarction and asymptomatic ventricular ectopic activity as studied by programmed electrical stimulation

In 22 patients with a previous myocardial infarction and documented Lown class II to IV asymptomatic ventricular arrhythmias, the arrhythmogenic effect of mexiletine (18 patients) and propafenone (10 patients) has been assessed by programmed electrical stimulation. Ventricular arrhythmias induced during the basal study were: repetitive ventricular responses (RVR) (11/22, 50%), nonsustained ventricular tachycardia (VT) (3/22, 14%), sustained VT (7/22, 32%) and ventricular fibrillation (VF) (1/22, 4%). The induction of sustained VT or VF increased to 50% after mexiletine and to 80% following propafenone. An arrhythmogenic effect was found in 7/11 patients (64%) without VT at the control study (P = 0.004). One patient of this group spontaneously developed sustained VT both after mexiletine and propafenone. Only 1/8 patients (13%) with sustained VT/VF at the basal study had RVR after drug administration. The R-R interval of sustained VT at the basal state tended to be faster than that after the drugs (260 +/- 60 ms vs 293 +/- 56 and 332 +/- 77 ms for mexiletine and propafenone, respectively) (P = 0.052). Statistical significance was only reached in the propafenone group (P = 0.03). Facilitation of VT induction after antiarrhythmic drugs is most likely due to a modest lengthening of refractoriness in contrast with a more evident reduction in conduction velocity within the reentry pathway. Our study illustrates that treating asymptomatic ventricular ectopic activity in patients with an old myocardial infarction may be dangerous and that antiarrhythmic drugs show a significant arrhythmogenic potential at least in the laboratory setting.

Efficacy of propafenone compared with quinidine in chronic ventricular arrhythmias

A double-blind, randomized study was designed to evaluate the efficacy of oral propafenone and oral quinidine in suppressing premature ventricular complexes (Ms). Twenty-five men were studied for 3 weeks. Twelve were randomized to the quinidine group and 13 to the propafenone group. Small doses of the drugs were administered for 1 week (200 mg of quinidine every 6 hours or 300 mg of propafenone every 12 hours) and large doses were administered for another week (400 mg of quinidine every 6 hours or 300 mg of propafenone every 8 hours). Strict criteria were used to define responders to antiarrhythmic therapy. For more than 85% reduction in total PVCs per hour: During the low-dose week, 36 % in the quinidine group and 50 % in the propafenone group were responders (difference not significant [NS]), while during the high-dose week 33% and 64% were responders (NS). For more than 95 % reduction of ventricular couplets per hour: During the low-dose week, 45% in each group were responders, while during the high-dose week, 56% and 60% were responders (NS). For 100% abolition of ventricular tachycardia (VT) beats per 24 hours: During the low-dose week, 60% in the quinidine group and 56 % in the propafenone group were responders (NS); during the high-dose week 80% and 67% were responders (NS). There was no significant difference in the 2 groups in incidence of side effects. This study shows comparable efficacy and tolerance of propafenone and quinidine for the control of ventricular arrhythmias in ambulatory patients with diverse forms of heart diseases.