Pharmacologic conversion of atrial fibrillation: a systematic review of available evidence

This report reviews the efficacy of currently available antiarrhythmic agents for conversion of atrial fibrilation (AF) to normal sinus rhythm (NSR). A systematic search of literature in the English language was done on computerized databases, such as MEDLINE, EMBASE, and Current Contents, in reference lists, by manual searching, and in contact with expert informants. Published studies involving humans that described the use of antiarrhythmic therapy for conversion of AF to NSR were considered and only studies that examined the use of agents currently available in the United States were included. Studies exclusively describing antiarrhythmic therapy for conversion of postsurgical AF were excluded. The methodology and results of each trial were assessed and attempts were made to acquire additional information from investigators when needed. Assessment of methodological quality was incorporated into a levels-of-evidence scheme. Eighty-eight trials were included, of which 34 (39%) included a placebo group (level I data). We found in recent-onset AF of less than 7 days, intravenous (i.v.) procainamide, high-dose i.v. or high-dose combination i.v. and oral amiodarone, oral quinidine, oral flecainide, oral propafenone, and high-dose oral amiodarone are more effective than placebo for converting AF to NSR. In recent-onset AF of less than 90 days, i.v. ibutilide is more effective than placebo and i.v. procainamide. In chronic AF, oral dofetilide converts AF to NSR within 72 hours, and oral propafenone and amiodarone are effective after 30 days of therapy. We conclude than for conversion of recent-onset AF of less than 7 days, procainamide may be considered a preferred i.v. agent and propafenone a preferred oral agent. For conversion of recent-onset AF of longer duration (less than 90 days), i.v. ibutilide may be considered a preferred agent. For patients with chronic AF and left ventricular dysfunction, direct current cardioversion is the preferred conversion method. Larger, well-designed randomized controlled trials with clinically important endpoints in specific populations of AF patients are needed.     

A comparative study of the efficacy and safety of procainamide versus propafenone versus amiodarone for the conversion of recent-onset atrial fibrillation

The appropriate treatment for the restoration of sinus rhythm in patients with atrial fibrillation (AF) of recent onset is still the subject of controversy. In this prospective, randomized, single-blind, placebo-controlled clinical study, we investigated the effectiveness and safety of procainamide, propafenone, and amiodarone, administered intravenously, for the conversion of recent-onset AF. We enrolled 362 consecutive patients (183 men; age 34 to 86 years; mean 65+/-10) with AF duration of no >48 hours. Of these patients, 89 were given procainamide, 91 propafenone, 92 amiodarone, and 90 placebo. Treatment was considered successful if conversion to sinus rhythm was achieved within the 24-hour study period. Baseline clinical characteristics were similar in the 4 groups. The treatment was successful in 61 of the 89 patients who received procainamide (68.53%; median time 3 hours), 73 of the 91 patients who received propafenone (80.21%; median time 1 hour), 82 of the 92 patients who received amiodarone (89.13%; median time 9 hours), and 55 of the 90 patients who received placebo (61.11%; median time 17 hours; p<0.05 for all medicated groups vs placebo; p<0.05 for amiodarone and propafenone vs procainamide). In conclusion, all 3 medications, when administered intravenously, are effective in the restoration of sinus rhythm in recent-onset AF. Amiodarone and propafenone are more effective whereas procainamide and propafenone are faster.     

A Review of Clinical Trials Assessing the Efficacy and Safety of Newer Antiarrhythmic Drugs in Atrial Fibrillation

Clinical trials assessing the efficacy of anti- arrhythmic drugs for terminating atrial fibrillation have demonstrated that rate control drugs have little to no added efficacy compared to placebo; however, spontaneous conversion of recent-onset atrial fibrillation is common. Antiarrhythmic drugs such as oral dofetilide, oral bolus-flecainide and propafenone and intravenous ibutilide all have a role in terminating atrial fibrillation. Active comparator trials have demonstrated that amiodarone is more efficacious in maintaining sinus rhythm than propafenone and sotalol. Multiple trials have demonstrated the safety of amiodarone, sotalol, dofetilide and azimilide in a post-myocardial infarction population and amiodarone and dofetilide in a congestive heart failure population. Newer antiarrhythmic agents, some with novel mechanisms of action, will add to the pharmacologic armamentarium in treating atrial fibrillation.     

Comparison of oral loading dose of propafenone and amiodarone for converting recent-onset atrial fibrillation. PARSIFAL Study Group

In patients with recent-onset atrial fibrillation (AF), restoration of sinus rhythm is considered to be the first-line therapeutic option. Although this conversion might be obtained by direct-current shock or intravenous antiarrhythmic drugs, administration of an oral loading dose of class I or III antiarrhythmic drugs is more simple and convenient. This prospective, randomized, multicenter study compares the time to conversion to sinus rhythm obtained with an oral loading dose of propafenone or amiodarone. Patients with recent-onset AF (<2 weeks), without contraindications for the 2 drugs, were randomly assigned to be treated with propafenone (600 mg for the first 24 hours and if necessary a repeated dose of 300 mg for 24 hours) or amiodarone (30 mg/kg for the first 24 hours and if necessary a repeated dose of 15 mg/kg for 24 hours). Exact conversion time during the first 24 hours was determined by Holter monitoring. In each treatment group 43 patients with the same baseline characteristics were included. The median time for restoration of sinus rhythm was shorter (p = 0.05) in the propafenone (2.4 hours) than in the amiodarone (6.9 hours) group. After 24 hours (56% in the propofenone and 47% in the amiodarone group) and 48 hours, the same proportion of patients in the 2 groups recovered sinus rhythm (no serious adverse events were noticed). Thus, oral loading dose of propafenone or amiodarone was safe with a similar conversion rate of recent-onset AF. Propafenone had a faster action.     

Cardioversion of recent-onset atrial fibrillation using intravenous antiarrhythmics: A European perspective

Pharmacological cardioversion using intravenous antiarrhythmic agents is commonly indicated in symptomatic patients with recent-onset atrial fibrillation (AF). Except in hemodynamically unstable patients who require emergency direct current electrical cardioversion, for the majority of hemodynamically stable patients, pharmacological cardioversion represents a valid option and requires the clinician to be familiar with the properties and use of antiarrhythmic agents. The main characteristics of selected intravenous antiarrhythmic agents for conversion of recent-onset AF, the reported success rates, and possible adverse events are discussed. Among intravenous antiarrhythmics, flecainide, propafenone, amiodarone, sotalol, dofetilide, ibutilide, and vernakalant are commonly used. Antazoline, an old antihistaminic agent with antiarrhythmic properties was also reported to give encouraging results in Poland. Intravenous flecainide and propafenone are the only Class I agents still recommended by recent guidelines. Intravenous new Class III agents as dofetilide and ibutilide have high and rapid efficacy in converting AF to sinus rhythm but require strict surveillance with electrocardiogram (ECG) monitoring during and after intravenous administration because of the potential risk of QT prolongation and Torsades de Pointes, which can be prevented and properly managed. Vernakalant, a partial atrial selective was shown to have a high success rate and to be safe in real-life use.     

Utility of adjunctive single oral bolus propafenone therapy in patients with atrial defibrillators.

AIMS: Previous studies have demonstrated that ambulatory atrial defibrillation shocks delivered by an implantable cardioverter-defibrillator (ICD) are safe and effective, but poorly tolerated. Separate studies have demonstrated the utility of single oral bolus propafenone for conversion of recent-onset atrial fibrillation (AF); however, most patients were hospitalized, had no structural heart disease, were taking no other antiarrhythmic drugs, and were not exposed to concomitant shock. We hypothesized that a single oral bolus dose of propafenone given early after onset would be a safe and effective adjunct to ICD-based AF therapy and improve overall therapy tolerance. METHODS AND RESULTS: A randomized three-way crossover study design was used to compare three strategies, deployed in the ambulatory setting early after AF episode onset in 35 ICD patients with advanced, drug refractory episodic/persistent syndromes, many of whom had structural heart disease and were taking other antiarrhythmic drugs: (i) single oral bolus propafenone (600 mg), followed by ICD shock if necessary; (ii) single oral bolus placebo, followed by ICD shock if necessary; and (iii) no oral bolus therapy and ICD shock if necessary (no bolus). Antiarrhythmic efficacy, defined by the restoration of sinus rhythm within 24 h, was similar during propafenone (81%) and no-bolus strategies (84%); both were significantly higher than during placebo strategy (62%). Propafenone was well tolerated and not associated with proarrhythmia. Shock use was significantly lower during propafenone strategy (19%) than during no-bolus strategy (55%); this was correlated with improved patient tolerance. CONCLUSION: Adjunctive use of single oral bolus propafenone is safe and effective in patients with an ICD and improves patient tolerance of device-based AF therapy.     

Amiodarone versus placebo and class Ic drugs for cardioversion of recent-onset atrial fibrillation: a meta-analysis

OBJECTIVES: This meta-analysis compared amiodarone with placebo and class Ic drugs for the cardioversion of recent-onset atrial fibrillation (AF), defined as lasting less than seven days. BACKGROUND: Despite the lack of trials that support its efficacy convincingly, amiodarone is widely used for conversion of recent-onset AF. METHODS: We searched Medline and EMBASE databases, as well as the Cochrane Controlled Trials Register for randomized trials on recent-onset AF comparing amiodarone to placebo or class Ic drugs. Data were combined according to a fixed effect model. The primary end point was the rate of conversion at 24 h. To study time-dependency of the drugs, efficacy at 1 to 2 h, 3 to 5 h, 6 to 8 h, and at 24 h was analyzed. RESULTS: We found six studies randomizing amiodarone versus placebo (595 patients) and seven studies versus class Ic drugs (579 patients). There was no significant difference between amiodarone and placebo at 1 to 2 h, but significant efficacy was found after 6 to 8 h (relative risk [RR] 1.23, p = 0.022) and at 24 h (RR 1.44, p < 0.001). Efficacy with amiodarone was inferior to class Ic drugs for up to 8 h (RR 0.67, p < 0.001) but no difference was seen at 24 h (RR 0.95, p = 0.50). There were no major adverse effects. CONCLUSIONS: Amiodarone is superior to placebo for cardioversion of AF, and even though the onset of conversion is delayed, its efficacy is similar at 24 h compared with class Ic drugs. These results favor amiodarone as a reasonable alternative for patients with recent AF in whom class Ic and other, more rapidly acting antiarrhythmic drugs cannot be used.     

Antiarrhythmic drugs

Opinion statement Both supraventricular and ventricular arrhythmias are associated with increased mortality and morbidity. Numerous antiarrhythmics have been developed in an attempt to decrease the frequency of these arrhythmias, hoping to improve survival and improve quality of life. Antiarrhythmic agents are a diverse group of drugs that affect various cardiac ionic channels and block specific arrhythmias. However, despite the suppression of these potentially lethal cardiac arrhythmias, only the β blockers have been shown to reduce sudden arrhythmic death, especially in patients with prior myocardial infarction or heart failure. Some antiarrhythmic agents can also worsen the index arrhythmia and caution must be used especially in the compromised patient. A simple guideline is as follows: For conversion of atrial fibrillation or flutter to sinus rhythm, in the absence of structural heart disease, intravenous ibutilide or oral propafenone or flecainide are good choices. For maintenance of sinus rhythm, propafenone or flecainide are logical choices. In the presence of structural heart disease, amiodarone, dofetilide, or dl sotalol are preferred. In heart failure, dofetilide or amiodarone are the logical choices. The role of antiarrhythmic therapy for ventricular arrhythmias is questionable and may be contraindicated, except for the use of β blockers. The implantable cardioverter-defibrillator is often used in patients at high risk. At times, the addition of an antiarrhythmic agent such as amiodarone may be justified.     

伊布利特与普罗帕酮转复心房颤动的疗效及电生理作用的差异

目的观察静脉注射伊布利特和普罗帕酮转复心房颤动(简称房颤)的疗效以及两种药物对心房和心室电生理作用的差异。方法采用随机、单盲对照研究,共入选房颤持续1~4 d的患者37例,随机进入伊布利特组(n=17)或普罗帕酮组(n=20)。两组分别静脉注射伊布利特1 mg或普罗帕酮70 mg,给药时间10 min,给药结束后10 min未转复窦性心律(简称窦律)者,重复上述治疗1次。观察给药开始后4h内房颤转复率,给药前后QRS波时限及校正的QT间期(QTc)间期变化,以及不良反应发生情况。结果①伊布利特组11例(64.7%)转复窦律,普罗帕酮组9例(45%)转复窦律,两组转复率无差异(P>0.05)。②给药后90 min内,伊布利特组QTc间期较用药前显著延长(506.4±53.6 ms vs 446.4±40.1 ms,P<0.001);QRS波时限有延长趋势(90.6±15.1 ms vs88.6±16.8 ms),但无统计学差异(P=0.07)。普罗帕酮组QRS波时限显著延长(96.9±20.4 ms vs 90.7±18.0 ms,P<0.01);QTc间期无显著差异(445.2±41.3 ms vs 440.5±22.1 ms,P>0.05)。③伊布利特组4例出现频发室性早搏、短阵室性心动过速。其中1例多形室性心动过速,发生在复律后窦性心动过缓伴QTc间期显著延长的病例。结论静脉注射伊布利特转复房颤有效,可致心室复极时间显著延长,应注意给药后短期内室性心律失常发生情况;普罗帕酮对心室复极时间无影响,可延长心室除极时间。     

Comparison of effectiveness of ranolazine plus amiodarone versus amiodarone alone for conversion of recent-onset atrial fibrillation

Ranolazine, an antianginal agent with antiarrhythmic properties, prevents atrial fibrillation (AF) in patients with acute coronary syndrome. In experimental models, the combination of ranolazine and amiodarone has marked synergistic effects that potently suppress AF. Currently, the clinical effect of the ranolazine-amiodarone combination for the conversion of AF is unknown. This prospective randomized pilot study compared the safety and efficacy of ranolazine plus amiodarone versus amiodarone alone for the conversion of recent-onset AF. We enrolled 51 consecutive patients with AF (<48-hour duration) eligible for pharmacologic cardioversion. Patients (33 men, 63 ± 8 years of age) were randomized to intravenous amiodarone for 24 hours (group A, n = 26) or to intravenous amiodarone plus oral ranolazine 1,500 mg at time of randomization (group A + R, n = 25). The 2 groups were well balanced with respect to clinical characteristics and left atrial diameter. Conversion within 24 hours (primary end point) was achieved in 22 patients (88%) in group A + R versus 17 patients (65%) in group A (p = 0.056). Time to conversion was shorter in group A + R than in group A (9.8 ± 4.1 vs 14.6 ± 5.3 hours, p = 0.002). According to Cox regression analysis, left atrial diameter and A + R treatment were the only independent predictors of time to conversion (hazard ratio 5.35, 95% confidence interval 2.37 to 12.11, p <0.001; hazard ratio 0.81, 95% confidence interval 0.74 to 0.88, p <0.001, respectively). There were no proarrhythmic events in either group. In conclusion, addition of ranolazine to standard amiodarone therapy is equally safe and appears to be more effective compared to amiodarone alone for conversion of recent-onset AF.     

Enhanced antiarrhythmic efficacy of propafenone when used in combination with procainamide or quinidine

This study evaluated the efficacy and safety of combining propafenone with procainamide or quinidine for treating ventricular arrhythmias in patients in whom procainamide or quinidine therapy alone failed to suppress arrhythmias. In 30 patients, the addition of propafenone resulted in a significant reduction of premature ventricular contraction (PVC) frequency compared to drug-free baseline (406 PVC/hr vs 33, p less than 0.001) and to procainamide or quinidine monotherapy (211 PVC/hr vs 27, p less than 0.01). Propafenone alone was also more effective than either procainamide or quinidine and resulted in significant suppression of PVC compared to the drug-free state (406 PVC/hr vs 38, p less than 0.001). However, higher propafenone doses were necessary during monotherapy as compared to propafenone therapy combined with procainamide or quinidine (730 mg/day vs 480 mg/day, p less than 0.001). Of the 30 patients, 22 required an increase in propafenone dose during monotherapy as compared to combination therapy. Thus, propafenone is an effective antiarrhythmic agent when used in combination with type IA antiarrhythmic drugs. With these combinations, lower doses of propafenone can be utilized effectively than with propafenone alone.     

Restoring Sinus Rhythm in Atrial Fibrillation: Electrical or Pharmacological Cardioversion

Restoration of sinus rhythm represents a desirable endpoint in patients with persistent (nonselfterminating) episode of paroxysmal atrial fibrillation (AF) and in selected patients with chronic AF. The decision whether to cardiovert AF pharmacologically or electrically is unresolved. Pharmacological cardioversion with oral quinidine first used to terminate recent onset AF is no longer used in Europe because its safety has been questioned. Other oral antiarrhythmic agents were used orally in this indication including procaînamide, disopyramide, and oral amiodarone. More recently, oral flecaînide and oral propafenone have been used in recent onset AF. Success rates ranging between 67% and 95% were reported in placebo-controlled studies. Pharmacological cardioversion can also routinely be obtained in hospital practice using intravenous injection of an antiarrhythmic agent. Intravenous digoxin, although commonly used, has shown in controlled studies to be no better than placebo. Intravenous amiodarone in open studies was associated with high success rates. Intravenous flecaînide, intravenous propafenone, and intravenous cibenzoline have been reported to be sucessful in recent onset AF. It is important to keep in mind that pharmacological cardioversion carries the risk of flutter with 1:1 conduction and ventricular proarrhythmia. The safety of pharmacological cardioversion using oral agents should be assessed in a hospital environment before allowing outpatient use. External (transthoracic) electrical cardioversion remains the technique of choice for restoring sinus rhythm in chronic AF. The success rates range from 65% to 90%. A technique of high energy electrical DC (200J or 300J) internal cardioversion has been shown to be useful in patients who failed external conversion. Recently, a technique for low-energy (> 6J) cardioversion of AF using biphasic shocks, electrode catheters positioned in the right atrium (cathode), and the coronary sinus (anode), was found to restore sinus rhythm in 70%-88% of patients. Internal cardioversion is emerging as a therapeutic alternative in selected groups of AF patients, particularly in those who failed external cardioversion.     

Successful conversion of recent-onset atrial fibrillation by sequential administration of up to three antiarrhythmic drugs

BACKGROUND: Short-term conversion attempt of recent-onset atrial fibrillation (AF) in the emergency room fails too often. Many patients and doctors still prefer pharmacological to electrical solutions in such cases. HYPOTHESIS: Sequential administration of up to 3 antiarrhythmic drugs of different classes of action (amiodarone, propafenone, and quinidine) may achieve conversion in such patients. METHOD: One hundred and forty consecutive patients with recent-onset AF were transferred to the intensive cardiac care unit after a failed 2-h conversion attempt in the emergency room. First-line drug for conversion was continued up to a full dose, and was chosen by AF etiology, or in recurrent AF episodes, empirically. In nonresponders, the failed drug was replaced by a drug of another class, and if the second-line drug failed it was replaced by a drug of the third-line. Electrical cardioversion was the final solution for nonresponders. RESULTS: Sixty percent of patients reached sinus rhythm by the first-line drug therapy, 34% by the second-line, and 4% by the third-line. Seventy-five percent of patients achieved conversion within 26 h, and 95% of patients achieved conversion within 40 h. Three patients were electrically cardioverted due to hemodynamical instability. Two episodes of Torsade de Pointes ventricular tachycardia were self-terminated. CONCLUSION: Sequential usage of up to 3 antiarrhythmic drugs of different classes of action provides almost complete success in conversion of recent-onset AF in patients refractory to short-term conversion attempt in the emergency room.     

Single oral loading dose of propafenone for pharmacological cardioversion of recent-onset atrial fibrillation

The efficacy and safety of the single dose oral loading regimen of propafenone for pharmacological cardioversion of recent-onset atrial fibrillation (AFib) was evaluated by analyzing the trials on the subject identified through a comprehensive literature search. Most of the trials used a single dose of 600 mg for oral loading. The success rates ranged from 56% to 83%, depending on the duration of AFib and follow-up after drug administration. The conversion time ranged from 110 +/- 59 to 287 +/- 352 min, depending on the duration of observation after drug administration. The single dose oral loading regimen of propafenone was significantly more efficacious than placebo in the first 8 h after administration but not at 24 h. Compared with the intravenous regimen, the oral regimen resulted in fewer conversions in the first 2 h, but both regimens were equally efficacious afterward. The oral propafenone regimen was as efficacious as the single dose oral loading regimen of flecainide but was superior to those of quinidine and amiodarone. The adverse effects reported were transient arrhythmia, reversible QRS-complex widening, transient hypotension and mild noncardiac side effects. The transient arrhythmias were chiefly at the time of conversion and included appearance of atrial flutter, bradycardia, pauses and junctional rhythm. No life-threatening proarrhythmic adverse effects were reported. The single oral loading dose of propafenone appears to be highly effective for conversion of recent-onset AFib, with a relatively rapid effect within 2 to 3 h and freedom from serious adverse effects.     

Serial antiarrhythmic therapy: role of amiodarone in prevention of atrial fibrillation recurrence--a lesson from the HOT CAFE Polish Study

Antiarrhythmic drug prophylaxis is known to improve long-term success of electrical cardioversion (CV) in persistent atrial fibrillation (AF). This prospective study evaluates the efficacy of sequential antiarrhythmic drug therapy in sinus rhythm (SR) maintenance after successful elective CV in patients with persistent nonvalvular AF. MATERIALS AND METHODS: One hundred and twenty-eight patients (61+/-8 years old) with persistent AF underwent CV. Mean AF duration preceding CV was 268+/-99 days. Following SR restoration, patients were treated sequentially with either of the following antiarrhythmic drugs: propafenone, sotalol or disopyramide. Where arrhythmia recurred, patients received another CV and a new drug from the range defined above. Where such treatment failed, patients were loaded with 14.0- to 16.0-gram doses of amiodarone and a third CV was performed. If the first CV failed to restore SR, patients received a loading dose of amiodarone followed by another CV. When successful, amiodarone was administered on continuous basis. RESULTS: The first CV proved successful in 55.5% of patients. During 1-year of follow-up, 31 patients (43.7%) presented with SR were treated with one antiarrhythmic agent (median does not exist). Application of the second drug proved to be effective in 6 patients (15.0%; median 13 days). Amiodarone was administered as the third antiarrhythmic agent to patients who had AF recurrence on the first two antiarrhythmic agents (propafenone, sotalol or disopyramide). It proved to be effective in 18 patients (52.9%; median does not exist) remaining free from AF for a period of 1 year as of commencement of the sequential antiarrhythmic therapy. Fifty-seven patients, in whom the first CV was ineffective, received amiodarone. During the loading period, SR was restored in 7 patients (12.3%). The remaining 50 patients underwent repeated CV, with SR restored in 37 (74.0%) of them. Long-term amiodarone treatment maintained SR in 30 (68.2%) patients during the follow-up period. Amiodarone helped to maintain SR in a total of 56.5% of patients. CONCLUSIONS: Amiodarone seems to be the drug most effectively restoring and maintaining SR in patients with persistent AF resistant to CV and standard antiarrhythmic drug prophylaxis.     

Effectiveness of amiodarone as a single oral dose for recent-onset atrial fibrillation

The efficacy of amiodarone has been proved in long-term maintenance of sinus rhythm (SR) in patients with paroxysmal atrial fibrillation (AF). The present study evaluates the efficacy and safety of a single oral dose of amiodarone in patients with recent-onset AF (<48 hours). Seventy-two patients were randomized to receive 30 mg/kg of either amiodarone or placebo. Conversion to SR was verified by 24-hour Holter monitoring. Ten patients were excluded because of SR in the beginning of monitoring or technical failure during Holter monitoring. The remaining study groups were comparable (n = 31 for each), except that in the placebo group beta blockers were more common. The patients receiving amiodarone converted to SR more effectively than those receiving placebo (p<0.0001). At 8 hours, approximately 50% of patients in the amiodarone group and 20% in the placebo group (Holter successful) had converted to SR, whereas after 24 hours the corresponding figures were 87% and 35%, respectively. The median time for conversion (8.7 hours for amiodarone and 7.9 hours for placebo) did not differ in the groups. Amiodarone was hemodynamically well tolerated, and the number of adverse events in the study groups was similar. Amiodarone as a single oral dose of 30 mg/kg appears to be effective and safe in patients with recent-onset AF.     

Safety and efficacy of intravenously administered tedisamil for rapid conversion of recent-onset atrial fibrillation or atrial flutter

OBJECTIVES: The goal of the present study was to assess the efficacy and safety of intravenous tedisamil, a new antiarrhythmic compound, for conversion of recent-onset atrial fibrillation (AF) or atrial flutter (AFL) to normal sinus rhythm (NSR). BACKGROUND: Tedisamil is a novel antiarrhythmic drug with predominantly class III activity. Its efficacy and safety for conversion of recent onset AF or AFL to NSR is not known. METHODS: This was a multicenter, double-blind, randomized, placebo-controlled, sequential ascending dose-group trial. A total of 201 patients with symptomatic AF or AFL of 3 to 48 h duration were enrolled in a two-stage study. During stage 1, patients were randomized to receive tedisamil at 0.4 mg/kg body weight or matching placebo; during stage 2, patients received tedisamil at 0.6 mg/kg body weight or matching placebo. Treatments were given as single intravenous infusions. The primary study end point consisted of the percentage of patients converting to NSR for at least 60 s within 2.5 h. RESULTS: Of 175 patients representing the intention-to-treat sample, conversion to NSR was observed in 41% (25/61) of the tedisamil 0.4 mg/kg group, 51% (27 of 53) of the tedisamil 0.6 mg/kg group, and 7% (4/59) of the placebo group (p < 0.001 for both tedisamil groups vs. placebo). Average time to conversion was 35 min in patients receiving tedisamil. There were two instances of self-terminating ventricular tachycardia: one episode of torsade de pointes and one of monomorphic ventricular tachycardia, both in patients receiving 0.6 mg/kg tedisamil. CONCLUSIONS: Tedisamil at dosages of 0.4 and 0.6 mg/kg was superior to placebo in converting AF or AFL. Tedisamil has a rapid onset of action leading to conversion within 30 to 40 min in the majority of responders.     

Advances in the acute pharmacologic management of cardiac arrhythmias

Safe and effective control of rapid ventricular rates in acute-onset atrial fibrillation (AF) can be accomplished with intravenous calcium antagonists, beta-blockers or amiodarone; digoxin is less effective. If pharmacologic cardioversion of AF is desired, single oral doses of propafenone or flecainide are safe and effective in patients without structural heart disease. Intravenous ibulitide is moderately effective in the conversion of persistent AF or atrial flutter, with a small risk of proarrhythmia. In wide QRS complex tachycardia of uncertain origin, adenosine and lidocaine are no longer recommended. Procainamide or amiodarone are the treatment options, but attempts should be made to define the origin of tachycardia. In the treatment of monomorphic ventricular tachycardia, lidocaine is no longer recommended; procainamide or amiodarone are the recommended therapies. In polymorphic ventricular tachycardia with a normal QT interval, beta-blockers are recommended. In shock-refractory ventricular fibrillation, lidocaine, and magnesium are ineffective; intravenous amiodarone should be the treatment of choice.     

Intravenous Procainamide for Predicting the Response of Sustained Ventricular Tachycardia to Type III Antiarrhythmic Drugs

The use of serial electrophysiology studies to guide antiarrhythmic drug therapy in patients with ventricular tachycardia is both costly and time consuming. Intravenous procainamide administered during of the initial electrophysiology study has previously been shown to be useful in predicting the efficacy of oral antiarrhythmic medications (type I and III). The purpose of this study is to confirm that ventricular tachycardia suppression after intravenous procainamide correlates with suppression on oral class III antiarrhythmic medications (amiodarone and sotalol). This study included all patients with sustained ventricular tachycardia who underwent an initial electrophysiology study including an acute suppression trial with intravenous procainamide and a subsequent restudy on oral amiodarone or sotalol. The response to intravenous procainamide was then compared with these type III antiarrhythmic medications. Between January 1993 and May 1995, 360 patients underwent electrophysiology studies for suspected or documented ventricular arrhythmias. One hundred patients (28%) had an inducible sustained ventricular tachycardia, and 26 patients received both intravenous procainamide and subsequently oral amiodarone or sotalol. Acute infusion of procainamide provided a highly specific method for predicting suppression of oral amiodarone and sotalol (82% and 100% respectively). However, several patients who were not suppressed by intravenous procainamide were suppressed by oral sotalol resulting in lower overall predictive accuracy 12/15 (80%) for amiodarone vs. 5/11 (45%) for sotalol treated group. We conclude that the acute infusion of procainamide may help to predict ventricular tachycardia suppression after oral amiodarone and sotalol. A larger prospective trial is warranted to confirm this finding.     

Amiodarone for pharmacological cardioversion of recent-onset atrial fibrillation

The efficacy and safety of amiodarone for pharmacological cardioversion of recent-onset atrial fibrillation was examined by reviewing the trials on the subject identified through a comprehensive literature search. Amiodarone has been used both intravenously (i.v.) and orally for the pharmacological cardioversion of recent-onset atrial fibrillation. Intravenous amiodarone has been used as a bolus only or as a bolus followed by a continuous i.v. infusion until conversion or up to 24 h. The dose of i.v. bolus given ranged from 3 to 7 mg/kg body weight and that of infusion from 900 to 3000 mg/day. The efficacy reported is 34-69% with the bolus only regimens, and 55-95% with the bolus followed by infusion regimens. Only the higher dose (>1500 mg/day) amiodarone is superior to placebo in converting recent-onset atrial fibrillation to sinus rhythm. The highest 24-h conversion rates have been reported with the i.v. regimen of 125 mg/h until conversion or a maximum of 3 g and the oral regimen of 25-30 mg/kg body weight administered as a single loading-dose (>90% and >85%, respectively). Most of the conversions occur after 6-8 h of the initiation of therapy. Predictors of successful conversion are shorter duration of atrial fibrillation, smaller left atrial size, and higher amiodarone dose. Amiodarone is not superior to the other antiarrhythmic drugs conventionally used for the pharmacological cardioversion of recent-onset atrial fibrillation but is relatively safe in patients with structural heart disease and in those with depressed left ventricle function. Therefore, amiodarone could be used particularly in patients with structural heart disease and in those with left ventricular systolic dysfunction as the use of class IC drugs, propafenone and flecainide, for cardioversion of atrial fibrillation is contraindicated in such patients.