Propafenone In Patients Research Articles

Safety and efficacy of long-term sodium channel blocker therapy for early rhythm control: the EAST-AFNET 4 trial

Abstract Background Clinical concerns exist about the potential proarrhythmic effects of the sodium channel blockers flecainide and propafenone (SCB) in patients with cardiovascular disease. Purpose SCB were used to deliver early rhythm control (ERC) therapy in EAST-AFNET 4. Methods We analysed the primary safety outcome (death, stroke, or serious adverse events related to rhythm-control therapy) and primary efficacy outcome (cardiovascular death, stroke and hospitalization for worsening of heart failure or acute coronary syndrome) during SCB-intake for ERC patients (n=1395) in EAST-AFNET 4. The protocol discouraged flecainide and propafenone in patients with reduced left ventricular ejection fraction and suggested stopping therapy upon QRS prolongation >25% on therapy. Results Flecainide or propafenone was given to 689 patients (age 69 (8) years; CHA2DS2-VASc 3.2 (1); 177 with heart failure; 41 with prior myocardial infarction, CABG or PCI and 26 with left ventricular hypertrophy >15mm; median therapy duration 1,153 [237, 1,828] days). The primary efficacy outcome occurred less often in patients treated with SCB (3/100 (99/3,316) patient-years) than in patients who never received SCB (SCBnever 4.9/100 (150/3,083) patient-years, p<0.001). There were numerically fewer primary safety outcomes in patients receiving SCB (2.9/100 (96/3,359) patient-years) than in SCBnever patients (4.2/100 (135/3,220) patient-years, adjusted p=0.015). Sinus rhythm at 2 years was similar between groups (SCB 537/610 (88); SCBnever 472/579 (82)). Conclusion Long-term therapy with flecainide or propafenone appeared to be safe in the EAST-AFNET 4 trial to deliver effective ERC therapy, including selected patients with stable cardiovascular disease such as coronary artery disease and stable heart failure.

Safety and efficacy of long-term sodium channel blocker therapy for early rhythm control: the EAST-AFNET 4 trial.

Clinical concerns exist about the potential proarrhythmic effects of the sodium channel blockers (SCBs) flecainide and propafenone in patients with cardiovascular disease. Sodium channel blockers were used to deliver early rhythm control (ERC) therapy in EAST-AFNET 4. We analysed the primary safety outcome (death, stroke, or serious adverse events related to rhythm control therapy) and primary efficacy outcome (cardiovascular death, stroke, and hospitalization for worsening of heart failure (HF) or acute coronary syndrome) during SCB intake for patients with ERC (n = 1395) in EAST-AFNET 4. The protocol discouraged flecainide and propafenone in patients with reduced left ventricular ejection fraction and suggested stopping therapy upon QRS prolongation >25% on therapy. Flecainide or propafenone was given to 689 patients [age 69 (8) years; CHA2DS2-VASc 3.2 (1); 177 with HF; 41 with prior myocardial infarction, coronary artery bypass graft, or percutaneous coronary intervention; 26 with left ventricular hypertrophy >15 mm; median therapy duration 1153 [237, 1828] days]. The primary efficacy outcome occurred less often in patients treated with SCB [3/100 (99/3316) patient-years] than in patients who never received SCB [SCBnever 4.9/100 (150/3083) patient-years, P < 0.001]. There were numerically fewer primary safety outcomes in patients receiving SCB [2.9/100 (96/3359) patient-years] than in SCBnever patients [4.2/100 (135/3220) patient-years, adjusted P = 0.015]. Sinus rhythm at 2 years was similar between groups [SCB 537/610 (88); SCBnever 472/579 (82)]. Long-term therapy with flecainide or propafenone appeared to be safe in the EAST-AFNET 4 trial to deliver effective ERC therapy, including in selected patients with stable cardiovascular disease such as coronary artery disease and stable HF. Clinical Trial Registration ISRCTN04708680, NCT01288352, EudraCT2010-021258-20, www.easttrial.org.

A comparative study of lappaconitine hydrobromide extended release and propafenone in patients with paroxysmal atrial fibrillation

A new dosage form of lappaconitine hydrobromide has been created – the long-acting drug Allaforte®, which has fewer side effects compared to the traditional dosage form (Allapinin®). Objective. To evaluate the effectiveness, safety and tolerability of Allaforte® therapy in comparison with the drug Rytmonorm® in patients with paroxysmal atrial fibrillation (AF). Material and methods. Patients who met the inclusion criteria and those who did not meet the non-inclusion criteria were randomized into 2 groups: 1st (n=50) – patients received Allaforte® 25 mg 3 times a day with an increase in dose to 50 mg 2 times a day when detected attack of AF; 2nd (n=50) – patients received Rytmonorm® 150 mg 3 times a day with an increase in dose to 300 mg 2 times a day if an attack of AF was detected. Results. The average time from the first dose of the drug to the development of AF paroxysm in the 1st group (Allaforte®) was 98.877±6.022 days, in the 2nd group (Rytmonorm®) – 98.808±5.876 days, the average time from the first dose of the drug to the completion of the study – 105.740±5.032 and 103.732±5.353 days, respectively. The drugs Allaforte® and Rytmonorm® equally improved the quality of life of patients. A comparative analysis in groups according to the severity of adverse events and their cause-and-effect relationship with the drug did not show significant differences. Conclusion. The study drugs showed comparable effectiveness in preventing attacks of AF with similar safety and tolerability.

プロパフェノン錠とフレカイニド錠の単回経口投与による発作性心房細動停止効果の比較研究

抗不整脈薬の単回経口投与による薬理学的除細動は，薬物の長期投与による副作用を回避し，心房細動（AF）の症状やリスクを早期に軽減する目的で行われる．われわれは，日本人のAF患者においてフレカイニドとプロパフェノンの単回経口投与の有効性と安全性を検討した．発作性AF患者29例をフレカイニド100mg（F群，n＝15；65±15歳），またはプロパフェノン150mg（P群, n＝14；61±12歳）にランダム化して単回経口投与を行い，投与後120分間の除細動成功率を比較検討した．患者背景は両群間で差を認めず，両群とも経時的な心拍数，血圧，QRS幅，QTc間隔の変動を認めなかった．除細動成功例はF群で3例（20％），P群で7例（50％）（p値＝0.09），洞調律回復までの時間はF群で70±17分，P群で77±34分であった（p値＝0.74）．F群で（非）通常型心房粗動（心拍数144/分）を1例認めた．F群の有効性が低かったものの両群間で有意差を認めず，日本人のAF患者に対して，本研究の薬物投与量ではほぼ安全に単回経口投与が行えることが示された．

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.

Intravenous administration of flecainide or propafenone in patients with recent-onset atrial fibrillation does not predict adverse effects during ‘pill-in-the-pocket’ treatment

BackgroundPill-in-the-pocket treatment should be prescribed only if the administration of a loading oral dose of flecainide or propafenone has been proved safe in hospital, since major adverse effects have been...

Extemporaneous Suspension of Propafenone: Attending Lack of Pediatric Formulations in Mexico

Physicians have frequently encountered difficulties when prescribing drugs not available in doses suitable for pediatric age groups. Furthermore, children have difficulty swallowing tablets. This study aimed to determine the stability of an oral propafenone suspension made from commercial tablets with a syrup vehicle and to establish its reliable use with children. An extemporaneous suspension of propafenone 1.5 mg/ml was prepared with commercial tablets. Its physicochemical and microbiologic stability was established by constant monitoring during 90 days at room temperature (15 +/- 5 degrees C) and at refrigeration (3-5 degrees C). Plasma levels of propafenona were measured in two children with supraventricular tachycardia at steady state. The suspension was stable, maintaining its original physicochemical and microbiologic properties. Moreover, no apparent changes in color or odor were observed. Plasma levels of propafenone in patients demonstrated therapeutic concentrations after they had taken the suspension, with no unwanted outcome. The conservation of both physicochemical and microbiologic stability of the suspension represents an option for the administration of propafenone to children.

Pharmacogenetic Study of the Response to Flecainide and Propafenone in Patients With Atrial Fibrillation

We analyzed cytochrome P450 2D6 polymorphism by determining phenotype as the metabolic ratio between dextromethorphan and its main metabolite, dextrorphan. We studied 18 men and 22 women in whom mean age was 54.6+/-11.9 years. In 9 patients metabolic ratio was determined before antiarrhythmic treatment and again during treatment, with a mean increase of 0.13+/-0.15 (P=.03). We found 19 poor metabolizers and 21 extensive metabolizers. Adverse effects were more frequent in poor metabolizers (21.1%) than in extensive metabolizers (4.8%; P=.12). Antiarrhythmic treatment was effective in 27 patients (67.5%), with no difference between poor and extensive metabolizers.

Symptomatic arrhythmia recurrence as an outcome in clinical trials of antiarrhythmic drug therapy

Atrial fibrillation is the most common cardiac arrhythmia requiring medical treatment, and developing new antiarrhythmic therapies remains a challenging problem. Documenting symptomatic arrhythmia recurrence using patient-activated ECG recording has been a useful tool to test new pharmacologic therapies. This technique has been used successfully to test immediate-release verapamil in patients with paroxysmal supraventricular tachycardia; flecainide acetate in patients with atrial fibrillation and paroxysmal supraventricular tachycardia; immediate-release propafenone in patients with atrial fibrillation and paroxysmal supraventricular tachycardia; d,l-sotalol in patients with atrial fibrillation; digoxin in patients with atrial fibrillation; azimilide dihydrochloride in patients with atrial fibrillation; and sustained-release propafenone in patients with atrial fibrillation. These studies have contributed to understanding efficacy and have led to regulatory approvals in the United States to label drugs as effective for supraventricular arrhythmias.

Acute Effect of Intravenous Propafenone for Atrial Fibrillation Refractory to Transthoracic Electrical Cardioversion

Background and Objectives：Various intravenous (IV antiarrhythmic drugs in patients with atrial fibrillation (AF refractory to electrical cardiooversion have been attempted. We assessed the efficacy of IV propafenone in patients with AF who failed to achieve normal sinus rhythm using standard external direct current (DC cardioversion. Subjects and Methods：Of the 77 AF patients who underwent a DC cardioversion, 18, who were refractory for up to a maximal 360 joules of external DC cardioversion, were included in this study. Propafenone was infused for 10 minutes at doses of 2 mg/kg (n＝3, 2.5 mg/kg (n＝8, and 3 mg/kg (n＝7 followed by repeated DC cardioversion. Results：The mean age of the patients receiving propafenone was 55±14 years and 21% were women. The mean ejection fraction and the average diameter of the left atrium were 56±5% and 42±7 mm, respectively. The AF cycle length increased following propafenone infusion form 160±23 ms to 278±62 ms (p<0.05. The AF converted to a normal sinus rhythm following propafenone infusion in three patients. Thirteen patients were successfully cardioverted following IV propafenone infusion, with a mean accumulated energy of 410±216 joules (689±373 joules prior to propafenone infusion, p<0.05. Cardioversion failed in 2 patients；therefore, the success rate of the cardioversion in patients who received IV propafenone was 88.9% (16/18. No significant adverse effects were observed. Conclusion：IV propafenone can be safely used to enhance the efficacy of cardioversion in patients with AF refractory to transthoracic DC cardioversion. ( ( ( (Korean Circulation J 2002;32 (10:878-883

Safety of oral propafenone in the conversion of recent onset atrial fibrillation to sinus rhythm:: A prospective parallel placebo-controlled multicentre study

Aim: Oral propafenone is effective in restoring sinus rhythm however the proarrhythmic effects are still unknown. The Safety Antiarrhythmic Therapy Evaluation (SATE) trial was a prospective randomized placebo-controlled multicentre study which evaluated the safety of acute oral loading dose of propafenone in patients with recent onset atrial fibrillation. Secondary end-points were to evaluate the effect of digitalis added to propafenone in ventricular rate control and the efficacy of propafenone alone or added to digitalis compared with efficacy of digitalis plus quinidine. Methods and results: 246 patients (126 male; 58±11 years) with atrial fibrillation of <48 h duration were randomly allocated to one of four groups: digitalis 0.75–1 mg i.v. plus quinidine 1100 mg (D+Q, 70 patients); propafenone 450–600 mg orally (PNF, 66 patients); propafenone 450–600 mg orally plus digitalis 0.750–1 mg i.v. (PNF+D, 70 patients); placebo (Pl, 40 patients). All patients underwent 24-h ECG Holter monitoring. Safety was assessed by evaluating the appearance of adverse events classified as mild, moderate and severe. No severe adverse events were reported. Short lasting asymptomatic atrial flutter episodes with atrio–ventricular conduction ≥2:1 were observed in 14% of the D+Q group, 21% PNF, 18% PNF+D and in 8% Pl. One patient in the D+Q group and four in the PNF+D group showed asymptomatic runs of 3–4 ventricular ectopic beats. Reversible sinus atrial blocks (<3 s) were detected in two patients of the D+Q group and in two of the PNF group. In patients with persistent atrial fibrillation the ventricular rate was similar in the four study groups. At 3 h the high efficacy of propafenone was confirmed. At the 24th hour no differences were found between active treatment and placebo arms. Conclusion: Propafenone in a single oral loading dose is safe and promptly effective in patients with recent onset atrial fibrillation.

Effects of Oral Propafenone in Patients with Frequent Ventricular Extrasystoles

Propafenone is an antiarrhythmic drug with class IC sodium channel blocking agent with mildly B-blocking and calcium channel blocking properties. Oral therapy effectively suppresses supraventricular and ventricular arrhythmias. However, experience with propafenone in Chinese patients is limited. To assess the efficacy and safety of oral propafenone in Chinese patients with frequent ventricular extrasys-toles(＞ 20/hour in average) and normal treadmill exercise test and echocardiographic results, 23patients (14 males and 9 females, mean age 56.5 years) were studied using 24-hour Holter ECG recording. Oral propafenone at a dose of 300 mg/day (12 patients) and 450 mg/day (11 patients) was then given. The 24-hour Holter ECG recording was repeated 4 weeks later to evaluate the suppressive effect of propafenone. Blood pressure and adverse effects were also recorded at each visit. When all patients taking 300 mg/day were analyzed as a group, no stastistically significant suppression of ventricular extrasystoles was noted, whereas patients taking 450 mg/day had significant suppression of total ventricular ectopies, isolated ventricular ectopies, and average ventricular ectopiees. Therapeutic success (＞85% suppression of ventricular ectop) was achieved in 41.7% (5/12) of in those taking 300 mg/day and in 63.6% (7/11) of those taking 450mg/day. Of the three patients taking 450 mg/day, who did not achieve ＞85% suppression, two patients showed significant suppression of ventricular ectopies without adverse effects when the dose was increased to 600 mg/day. During the treatment period, no patient reported arrhythmia-related ill effects or developed hemodynamic instability, although three patients had transient and asymptomatic bradycardia during the 24-hour Holter ECG recording. Therefore, we conclude that oral propafenone is effective at a dose range of 300 to 600 mg/day is effective and safe in the suppression of frequent ventricular extrasystoles in patients with functionally normal heart.(Tzu Chi Med J 1997;9:259-264)

Effects of oral propafenone on defibrillation and pacing thresholds in patients receiving implantable cardioverter-defibrillators

The effects of propafenone, a predominantly class IC antiarrhythmic drug, on defibrillation and pacing thresholds were evaluated in patients undergoing cardioverter-defibrillator implantation. Previous studies have shown that the class IC agents encainide and flecainide may increase the energy requirements for pacing and defibrillation. Animal studies with propafenone have shown inconsistent results regarding its effect on defibrillation energy requirements. This report investigated the effects of propafenone on defibrillation and pacing thresholds in humans. After cardioverter-defibrillator implantation, 47 patients were enrolled in a double-blind, three-way parallel, randomized trial of 450 mg/day (Group 1) or 675 mg/day (Group 2) of oral propafenone or placebo (Group 3) for 3 to 7 days. Predischarge defibrillation and pacing thresholds after treatment were compared with baseline thresholds obtained at implantation. There was no statistically significant difference between implantation and predischarge defibrillation thresholds in the three groups (Group 1: [mean +/- SE] 11.0 +/- 1.3 vs. 12.1 +/- 1.5 J; Group 2: 11.5 +/- 1.1 vs. 13.6 +/- 1.3 J; Group 3: 12.5 +/- 1.2 vs. 13.3 +/- 1.6 J), and no significant difference between treatment groups was found with a 0.86 power to detect a 5-J difference between groups. Paired pulse width pacing thresholds at 2.8 V were compared in 14 patients. A small increase of 0.02 ms was noted at predischarge testing in patients treated with propafenone and placebo. Short-term oral propafenone (450 and 675 mg/day) does not significantly affect defibrillation or pacing thresholds. Concomitant use of propafenone in patients with implantable cardioverter-defibrillators with recurrent ventricular or atrial tachyarrhythmias should not interfere with proper device function.

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.

Propafenone-mexiletine combination for the treatment of sustained ventricular tachycardia

Objectives. The purpose of this study was to explore the efficacy of combined therapy with propafenone and mexiletine for control of sustained ventricular tachycardia.Background. Combination antiarrhythmic drug therapy may enhance efficacy and lead to control of ventricular arrhythmias in some patients. Few reports have studied the combination of class IB and class IC drugs. Thus, this study was designed to investigate a combination of mexiletine and propafenone in patients with refractory ventricular tachycardia.Methods. Sixteen patients with sustained ventricular tachycardia had their clinical arrhythmia induced by programmed stimulation. Procainamide and propafenone alone failed to prevent reinduction of tachycardia in all. Mexiletine was subsequently added to propafenone and programmed stimulation was repeated.Results. With combination therapy ventricular tachycardia was noninducible in three patients (19%). A fourth who had presented with polymorphic ventricular tachycardia had slow bundle branch reentry (cycle length 500 ms) induced, in the other 12, tachycardia cycle length increased from 262 ± 60 ms at baseline to 350 ± 82 ms with propafenone and to 390 ± 80 ms with propafenone plus mexiletine (p < 0.0001 compared with baseline). Hemodynamic deterioration requiring defibrillation occurred in six patients at baseline study, in five taking propafenone and in two taking both drugs.Conclusions. The combination of propafenone and mexiletine is effective in suppressing the induction of ventricular tachycardia in some patients refractory to procainamide and propafenone alone. In those in whom ventricular tachycardia could still be induced, the rate was slower and hemodynamically tolerated.

A multicentre, randomized trial on the benefit/risk profile of amiodarone, flecainide and propafenone in patients with cardiac disease and complex ventricular arrhythmias

A multicentre, randomized trial on the benefit/risk profile of amiodarone, flecainide and propafenone in patients with cardiac disease and complex ventricular arrhythmias

Washout of long-term treatment with flecainide and propafenone in patients with complex ventricular arrhythmias and cardiac disease

To assess the spontaneous variability of ventricular arrhythmias after withdrawal of apparently successful antiarrhythmic therapy, we enrolled in a washout protocol 40 patients who had completed a randomized controlled 2-year study of antiarrhythmic drugs (the Antiarrhythmic Drug Evaluation Group [ADEG] study). All of them had heart disease and were first seen with high-grade ventricular arrhythmias (Lown class 4a and 4b) at enrollment. After 2 years all of them had responded to propafenone or flecainide; patients who completed the study on a regimen of amiodarone were not considered for the washout study. A total of 27 patients discontined flecainide and 13 propafenone. Seven days after withdrawal they underwent 24- or 48-hour ECG testing and were classified as true responders (TR) if the arrhythmias were present at the same level as 2 years previously and false responders (FR) if they were below the ADEG responsiveness level. TR patients had a third 24-hour ECG 7 days later, after rechallenge with the same treatment, and FR patients had a third ECG without drugs. Adherence to the protocol was ascertained by measuring drug plasma concentrations at every 24-hour ECG recording. No differences were found in distribution of heart disease and grade of ventricular arrhythmias between patients in the washout study and the remaining group of the ADEG trial. Twenty-four of 40 patients (60%) were true responders. In 4 of the 17 patients who had a third 24 hour ECG, the responsiveness to the same drug was not confirmed. Sixteen of 40 patients were false responders (40%); in all but 1 of 15 patients who had a third 24-hour ECG, the FR status was confirmed. No difference was found between FR and TR patients with regard to heart disease, basal level of ventricular arrhythiias, echo parameters at enrollment, number of drugs changed during the ADEG trial, and last drug taken. Long-term variability of ventricular ectopic beats, couplets, and runs ≥3 consecutive beats (ratio between log of arrhythmic events in washout and enrollment 24-hour ECGs) was significantly higher in FR patients. Our data suggest that an average proportion of patients with heart disease and complex ventricular arrhythmias has a spontaneous reduction of the same arrhythmias over 2 years. No variables predictive of this behavior were found. A periodic reassessment of arrhythmic patterns after drug washout is therefore needed and, as shown, is feasible.

Acute and Long-Term Efficacy of Oral Propafenone in Patients with Ventricular Tachyarrhythmias

The class Ic antiarrhythmic agent propafenone was studied by repeated electrophysiologic testing in 54 patients (43 male, aged 54 +/- 10 years, mean ejection fraction of 37.3 +/- 16.9%) with ventricular tachyarrhythmias. Forty patients (74%) had coronary artery disease. Programmed ventricular stimulation (S2, S2S3 during sinus rhythm and/or during S1S1 = 500, 430, 370, and 330 ms) off antiarrhythmic drugs induced sustained ventricular tachycardia, flutter, or fibrillation in all patients. After 450-900 mg of oral propafenone/day for 4-7 days, 51 patients were restudied. In the remaining three patients, spontaneous ventricular tachycardia occurred on drug therapy. Tachycardia induction was suppressed in 9 of 51 patients restudied (18%) and rendered more difficult to induce (basic stimulation drive greater than or equal to 40 beats/min higher than at control study) in another 7 patients (14%) (overall efficacy of 31%). The tachycardia rate decreased from 220 +/- 43 to 177 +/- 44 beats/min (p less than 0.01). The right ventricular effective refractory period increased from 232 +/- 22 to 252 +/- 22 ms (p less than 0.001). Responders to propafenone therapy had higher rates of inducible ventricular tachycardia at control (greater than 230 beats/min: 43%; less than or equal to 230 beats/min: 21%; p less than 0.05), higher ejection fractions, and lower left ventricular end-diastolic pressures than nonresponders. Eleven of the 16 patients showing a positive response to propafenone therapy in electrophysiologic testing were discharged on propafenone alone. During follow-up (17 +/- 12 months), nine patients remained free from ventricular tachycardia, one patient had a relapse, and one patient died of noncardiac death.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute and long-term efficacy of propafenone in patients with sustained ventricular tachyarrhythmias: assessment with programmed ventricular stimulation

To determine the electrophysiological properties of oral propafenone, 50 patients (39 male and 11 female, aged 31 to 80 years) with sustained ventricular tachycardia or ventricular fibrillation underwent serial electrophysiological drug testing, using propafenone (750 to 900 mg daily) as the anti-arrhythmic regimen of first choice. During baseline study, all patients had inducible sustained ventricular tachyarrhythmias. After oral loading of propafenone, 37 patients (74%) remained inducible whereas 13 were rendered non-inducible. Among the still inducible patients, the mean VT rate decreased from 223 +/- 38 b.min-1 (baseline) to 172 +/- 32 b.min +/- 1 (P less than 0.001). Four patients showed an increase of VT rate during propafenone compared to the VT rate at control. Non-inducible patients were discharged on propafenone. During a mean follow-up period of 20 +/- 15 months, there were three non-fatal VT recurrences among the responders, two of them due to non-compliance. Thus, propafenone used as the anti-arrhythmic agent of first choice among patients undergoing serial electrophysiological drug testing for ventricular tachyarrhythmias proved effective in suppressing VT induction in 26%. With regard to arrhythmic events, these patients have a favourable outcome.

The use of associated propafenone in patients with amiodarone-resistant ventricular tachycardia

To clarify the risk-benefit ratio involved in association of antiarrhythmic drugs, a combined therapy of amiodarone and propafenone was tested by means of continuous electrocardiographic monitoring, analysis of levels of the drug in the plasma and programmed electrical stimulation in a selected group of 10 patients who had left ventricular dysfunction and spontaneous relapses of sustained ventricular tachycardia despite treatment with amiodarone. Induction of sustained ventricular tachycardia, possible in each case during treatment with amiodarone, was suppressed after addition of propafenone in 2 patients (responders), who had the best ejection fractions of the entire group (> 45%). Worsening of spontaneous tachycardias developed in 4 cases during the combined therapy. These ventricular arrhythmias, although generally at a low rate, sometimes had the potential to degenerate into ventricular fibrillation and disappeared after both discontinuation of propafenone or increase of its dosage (1 patient). Of the six cases undergoing chronic combined treatment, only the responders to premature electrical stimulation were completely protected from recurrences of arrhythmia. Three cases, on the other hand, needed permanent endocardial pacing for symptomatic bradyarrhythmias. The combination of treatment with amiodarone and propafenone, although potentially useful in limiting dosages of and toxicity from amiodarone, is frequently associated with undersirable, and occasionally has severe, side-effects. The best candidates for this pharmacological association seem to be patients without severely depressed left ventricular function who have a greater probability of not presenting the inducibility of ventricular tachycardia after the addition of propafenone to the regimen for treatment.