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Bradley P. Knight - One of the best experts on this subject based on the ideXlab platform.
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comparison of amiodarone versus Ibutilide for the prevention of immediate recurrences of atrial fibrillation during pulmonary vein isolation
American Journal of Cardiology, 2002Co-Authors: Hakan Oral, Hiroshi Tada, Frank Pelosi, Mehmet Ozaydin, Aman Chugh, Sohail Hassan, Christoph Scharf, Steve W K Lai, Radmira Greenstein, Bradley P. KnightAbstract:During segmental ostial ablation for pulmonary vein isolation, pulmonary vein potentials are easily identified during sinus rhythm or left atrial pacing. Therefore, maintenance of atrial fibrillation (AF) during the procedure is desirable. However, cardioversion is occasionally followed by an immediate recurrence of AF. This study compared the efficacy of Ibutilide and amiodarone in preventing immediate recurrences of AF in patients who underwent pulmonary vein isolation. The subjects of this study were 25 patients (mean age 56 ± 10 years) who underwent pulmonary vein isolation for AF who had an immediate recurrence of AF within 60 seconds after 2 transthoracic cardioversions. The patients were randomized to receive an infusion of either 300 mg of amiodarone over 10 minutes or 1 mg of Ibutilide over 5 minutes. Cardioversion was repeated 15 minutes after the drug infusion. If immediate recurrences of AF occurred 2 more times, the alternative study drug was administered, and cardioversion was repeated. Immediate recurrences of AF were suppressed by amiodarone in 8 of 10 patients (80%), and by Ibutilide in 9 of 15 patients (60%, p = 0.4). After crossover, immediate recurrence of AF was suppressed in 2 of 6 patients (33%) by amiodarone, and in 1 of 2 patients (50%) by Ibutilide (p = 0.6). Ibutilide and amiodarone, when used alone or in combination, prevented immediate recurrences of AF in 20 of 25 patients (80%). There were no adverse drug effects. Ibutilide and amiodarone were equally effective in suppressing immediate recurrences of AF. Overall, immediate recurrences of AF can be prevented by amiodarone and/or Ibutilide in 80% of patients.
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Effects of verapamil and Ibutilide on atrial fibrillation and postfibrillation atrial refractoriness
Journal of cardiovascular electrophysiology, 2002Co-Authors: Christian Sticherling, William Hsu, Hiroshi Tada, C B S Anton Bares, Hakan Oral, Frank Pelosi, Bradley P. Knight, S. Adam Strickberger, Fred MoradyAbstract:VerapamilandIbutilide. Introduction: Early recurrence of atrial e brillation (AF) after cardioversion may be related to shortening of the atrial effective refractory period (ERP). This study compared the effects of verapamil and Ibutilide on AF cycle length (AFCL), atrial ERP, and susceptibility to recurrent AF. Methods and Results: In 33 adults, the atrial ERP was measured at basic drive CLs of 350 and 500 msec before and after a brief episode of pacing-induced AF. During AF, verapamil, Ibutilide, or saline was infused in 11 patients each. Shortening of the post-AF atrial ERP was attenuated by verapamil and prevented by Ibutilide. AFCL shortened by 32 6 21 msec in the verapamil group (P 10 minutes was induced more often in the verapamil group than in the Ibutilide group (26% vs 0%; P 5 0.01). Another 10 patients received verapamil or Ibutilide in the absence of AF. Atrial ERP was unchanged after verapamil and prolonged after Ibutilide. Conclusion: Verapamil shortens AFCL and impedes the conversion of induced AF, whereas Ibutilide prolongs AFCL and does not impede the early conversion of induced AF. Ibutilide is more effective than verapamil in preventing post-AF shortening of the atrial ERP and reducing the susceptibility toward
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Cost analysis of transthoracic cardioversion of atrial fibrillation with and without Ibutilide pretreatment.
Journal of cardiovascular pharmacology and therapeutics, 2000Co-Authors: Hakan Oral, Christian Sticherling, Frank Pelosi, Bradley P. Knight, Michael H. Kim, Robert L. Baker, Steven P. Chough, Kristina Wasmer, Gregory F. Michaud, A. Mark FendrickAbstract:Background: Ibutilide may result in chemical cardioversion of atrial fibrillation and facilitates transthoracic cardioversion by lowering the defibrillation energy requirement. Whether routine pretreatment with Ibutilide increases or decreases the cost of cardioversion is unknown. The purpose of this study was to compare the cost of outpatient transthoracic cardioversion of atrial fibrillation with and without Ibutilide pretreatment.Methods: Using a model based on published literature and hospital accounting information, a hypothetical group of 100 patients with atrial fibrillation and a left ventricular ejection fraction >0.30 underwent 2 strategies of outpatient cardioversion: transthoracic cardioversion with and without routine pretreatment with 1 mg Ibutilide, and with and without involvement of an anesthesiologist for sedation. If transthoracic cardioversion was unsuccessful in patients who did not receive Ibutilide, transthoracic cardioversion was repeated after administration of Ibutilide.Results: ...
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Facilitating transthoracic cardioversion of atrial fibrillation with Ibutilide pretreatment.
The New England journal of medicine, 1999Co-Authors: Hakan Oral, Bradley P. Knight, Gregory F. Michaud, Joseph Souza, Rajiva Goyal, S A Strickberger, Fred MoradyAbstract:Background Atrial fibrillation cannot always be converted to sinus rhythm by transthoracic electrical cardioversion. We examined the effect of Ibutilide, a class III antiarrhythmic agent, on the energy requirement for atrial defibrillation and assessed the value of this agent in facilitating cardioversion in patients with atrial fibrillation that is resistant to conventional transthoracic cardioversion. Methods One hundred patients who had had atrial fibrillation for a mean (±SD) of 117±201 days were randomly assigned to undergo transthoracic cardioversion with or without pretreatment with 1 mg of Ibutilide. We designed a step-up protocol in which shocks at 50, 100, 200, 300, and 360 J were used for transthoracic cardioversion. If transthoracic cardioversion was unsuccessful in a patient who had not received Ibutilide pretreatment, Ibutilide was administered and transthoracic cardioversion attempted again. Results Conversion to sinus rhythm occurred in 36 of 50 patients who had not received Ibutilide (72 ...
Hakan Oral - One of the best experts on this subject based on the ideXlab platform.
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comparison of amiodarone versus Ibutilide for the prevention of immediate recurrences of atrial fibrillation during pulmonary vein isolation
American Journal of Cardiology, 2002Co-Authors: Hakan Oral, Hiroshi Tada, Frank Pelosi, Mehmet Ozaydin, Aman Chugh, Sohail Hassan, Christoph Scharf, Steve W K Lai, Radmira Greenstein, Bradley P. KnightAbstract:During segmental ostial ablation for pulmonary vein isolation, pulmonary vein potentials are easily identified during sinus rhythm or left atrial pacing. Therefore, maintenance of atrial fibrillation (AF) during the procedure is desirable. However, cardioversion is occasionally followed by an immediate recurrence of AF. This study compared the efficacy of Ibutilide and amiodarone in preventing immediate recurrences of AF in patients who underwent pulmonary vein isolation. The subjects of this study were 25 patients (mean age 56 ± 10 years) who underwent pulmonary vein isolation for AF who had an immediate recurrence of AF within 60 seconds after 2 transthoracic cardioversions. The patients were randomized to receive an infusion of either 300 mg of amiodarone over 10 minutes or 1 mg of Ibutilide over 5 minutes. Cardioversion was repeated 15 minutes after the drug infusion. If immediate recurrences of AF occurred 2 more times, the alternative study drug was administered, and cardioversion was repeated. Immediate recurrences of AF were suppressed by amiodarone in 8 of 10 patients (80%), and by Ibutilide in 9 of 15 patients (60%, p = 0.4). After crossover, immediate recurrence of AF was suppressed in 2 of 6 patients (33%) by amiodarone, and in 1 of 2 patients (50%) by Ibutilide (p = 0.6). Ibutilide and amiodarone, when used alone or in combination, prevented immediate recurrences of AF in 20 of 25 patients (80%). There were no adverse drug effects. Ibutilide and amiodarone were equally effective in suppressing immediate recurrences of AF. Overall, immediate recurrences of AF can be prevented by amiodarone and/or Ibutilide in 80% of patients.
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Effects of verapamil and Ibutilide on atrial fibrillation and postfibrillation atrial refractoriness
Journal of cardiovascular electrophysiology, 2002Co-Authors: Christian Sticherling, William Hsu, Hiroshi Tada, C B S Anton Bares, Hakan Oral, Frank Pelosi, Bradley P. Knight, S. Adam Strickberger, Fred MoradyAbstract:VerapamilandIbutilide. Introduction: Early recurrence of atrial e brillation (AF) after cardioversion may be related to shortening of the atrial effective refractory period (ERP). This study compared the effects of verapamil and Ibutilide on AF cycle length (AFCL), atrial ERP, and susceptibility to recurrent AF. Methods and Results: In 33 adults, the atrial ERP was measured at basic drive CLs of 350 and 500 msec before and after a brief episode of pacing-induced AF. During AF, verapamil, Ibutilide, or saline was infused in 11 patients each. Shortening of the post-AF atrial ERP was attenuated by verapamil and prevented by Ibutilide. AFCL shortened by 32 6 21 msec in the verapamil group (P 10 minutes was induced more often in the verapamil group than in the Ibutilide group (26% vs 0%; P 5 0.01). Another 10 patients received verapamil or Ibutilide in the absence of AF. Atrial ERP was unchanged after verapamil and prolonged after Ibutilide. Conclusion: Verapamil shortens AFCL and impedes the conversion of induced AF, whereas Ibutilide prolongs AFCL and does not impede the early conversion of induced AF. Ibutilide is more effective than verapamil in preventing post-AF shortening of the atrial ERP and reducing the susceptibility toward
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Cost analysis of transthoracic cardioversion of atrial fibrillation with and without Ibutilide pretreatment.
Journal of cardiovascular pharmacology and therapeutics, 2000Co-Authors: Hakan Oral, Christian Sticherling, Frank Pelosi, Bradley P. Knight, Michael H. Kim, Robert L. Baker, Steven P. Chough, Kristina Wasmer, Gregory F. Michaud, A. Mark FendrickAbstract:Background: Ibutilide may result in chemical cardioversion of atrial fibrillation and facilitates transthoracic cardioversion by lowering the defibrillation energy requirement. Whether routine pretreatment with Ibutilide increases or decreases the cost of cardioversion is unknown. The purpose of this study was to compare the cost of outpatient transthoracic cardioversion of atrial fibrillation with and without Ibutilide pretreatment.Methods: Using a model based on published literature and hospital accounting information, a hypothetical group of 100 patients with atrial fibrillation and a left ventricular ejection fraction >0.30 underwent 2 strategies of outpatient cardioversion: transthoracic cardioversion with and without routine pretreatment with 1 mg Ibutilide, and with and without involvement of an anesthesiologist for sedation. If transthoracic cardioversion was unsuccessful in patients who did not receive Ibutilide, transthoracic cardioversion was repeated after administration of Ibutilide.Results: ...
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Facilitating transthoracic cardioversion of atrial fibrillation with Ibutilide pretreatment.
The New England journal of medicine, 1999Co-Authors: Hakan Oral, Bradley P. Knight, Gregory F. Michaud, Joseph Souza, Rajiva Goyal, S A Strickberger, Fred MoradyAbstract:Background Atrial fibrillation cannot always be converted to sinus rhythm by transthoracic electrical cardioversion. We examined the effect of Ibutilide, a class III antiarrhythmic agent, on the energy requirement for atrial defibrillation and assessed the value of this agent in facilitating cardioversion in patients with atrial fibrillation that is resistant to conventional transthoracic cardioversion. Methods One hundred patients who had had atrial fibrillation for a mean (±SD) of 117±201 days were randomly assigned to undergo transthoracic cardioversion with or without pretreatment with 1 mg of Ibutilide. We designed a step-up protocol in which shocks at 50, 100, 200, 300, and 360 J were used for transthoracic cardioversion. If transthoracic cardioversion was unsuccessful in a patient who had not received Ibutilide pretreatment, Ibutilide was administered and transthoracic cardioversion attempted again. Results Conversion to sinus rhythm occurred in 36 of 50 patients who had not received Ibutilide (72 ...
Kenneth A Ellenbogen - One of the best experts on this subject based on the ideXlab platform.
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Clinical and electrophysiologic effects of calcium channel blockers in patients receiving Ibutilide.
American heart journal, 2002Co-Authors: Mark A. Wood, Bruce S Stambler, David M. Gilligan, Chris Brown-mahoney, Fatemeh Nematzadeh, Kenneth A EllenbogenAbstract:Abstract Background Ibutilide is indicated for the acute termination of atrial fibrillation and atrial flutter. Recent work concludes that Ibutilide activates a late inward sodium current that is blocked by nifedipine. Because calcium channel blockers are commonly used in patients with atrial fibrillation, it is important to exclude an antagonistic effect on Ibutilide in the clinical setting. Methods We performed a retrospective electrocardiographic (ECG) review of patients enrolled in 3 clinical trials of Ibutilide (2 atrial fibrillation conversion protocols and 1 ventricular tachycardia suppression protocol) to determine clinical efficacy and ECG effects of Ibutilide in patients receiving and not receiving calcium channel blockers. Calcium channel blockers were administered as clinically indicated. A meta-analysis of the effects of calcium channel blockers on the conversion efficacy of atrial fibrillation and atrial flutter by Ibutilide was also performed for studies in the literature. Results One hundred thirty patients were included in the ECG analysis (106 from atrial fibrillation protocols and 24 from the ventricular tachycardia protocol). Sixty-eight of the 130 patients were taking calcium channel blockers at the time of Ibutilide administration. There were no differences in the QT or QTc intervals, conversion rate for atrial fibrillation or atrial flutter, or suppression of ventricular tachycardia between patients taking and not taking calcium channel blockers. In the meta-analysis of 4 studies, there was no difference in the conversion rates between patients taking (52%, n = 221) and not taking (45%, n = 402) calcium channel blockers ( P =.09). Conclusions In the clinical setting, the concomitant use of calcium channel blockers does not alter the ECG effects or efficacy of Ibutilide for the treatment of atrial or ventricular arrhythmias. (Am Heart J 2002;143:176-80.)
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antiarrhythmic actions of intravenous Ibutilide compared with procainamide during human atrial flutter and fibrillation electrophysiological determinants of enhanced conversion efficacy
Circulation, 1997Co-Authors: Bruce S Stambler, Mark A. Wood, Kenneth A EllenbogenAbstract:Background The selective class III antiarrhythmic agent Ibutilide prolongs action potential duration and terminates atrial flutter (AFL) and fibrillation (AF), but the mechanism of its antiarrhythmic efficacy in humans has not been fully characterized. This study compared the antiarrhythmic effects of Ibutilide with the class IA agent procainamide in humans during AFL and AF. Antiarrhythmic drug actions and electrophysiological characteristics of AFL and AF that enhanced pharmacological termination were investigated. Methods and Results Right atrial monophasic action potentials were recorded during 148 episodes of AFL (n=89) or AF (n=59) in 136 patients treated with intravenous Ibutilide (n=73) or placebo (n=22) as participants in randomized, double-blinded comparative studies or intravenous procainamide (n=53) in a concurrent open-label study. The conversion rates in AFL with Ibutilide, procainamide, and placebo were 64% (29 of 45 patients), 0% (0 of 33), and 0% (0 of 11), respectively, whereas in AF the rates were 32% (9 of 28), 5% (1 of 20), and 0% (0 of 11), respectively. In AFL, Ibutilide increased atrial monophasic action potential duration (MAPD) more (30% versus 18%, P <.001) and prolonged atrial cycle length (CL) less (16% versus 26%, P <.001) than procainamide. Ibutilide shortened and procainamide prolonged action potential diastolic interval during AFL (−12% versus 51%, P <.001). Ibutilide increased MAPD/CL ratio, whereas procainamide tended to decrease this ratio (13% versus −6%, P <.01). In AF, Ibutilide and procainamide induced similar increases in atrial CL (48% versus 45%), but Ibutilide induced a greater increase in MAPD (52% versus 37%, P <.05). Independent electrophysiological predictors of pharmacological arrhythmia termination were increase in MAPD/CL ratio ( P =.005) in AFL and longer baseline mean MAPD ( P =.011) in AF. Termination of AFL with Ibutilide was characterized by significant increases in beat-to-beat atrial CL, MAPD, and diastolic interval variability. Ibutilide was significantly more effective in converting AF when the mean atrial CL was ≥160 ms (64% versus 0%, P <.001) or MAPD was ≥125 ms (57% versus 0%, P =.002) at baseline. Conclusions Enhanced conversion efficacy of Ibutilide compared with procainamide in AFL is correlated with a relatively greater prolongation of atrial MAPD than atrial CL, and termination of AFL by Ibutilide is characterized by oscillations in atrial CL and MAPD. Conversion of AF by Ibutilide is enhanced by a longer baseline mean atrial CL or MAPD.
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Acute hemodynamic effects of intravenous Ibutilide in patients with or without reduced left ventricular function.
The American journal of cardiology, 1997Co-Authors: Bruce S Stambler, Kenneth A Ellenbogen, Karen J. Beckman, Alan H. Kadish, John Camm, Kim T. Perry, James T. VanderlugtAbstract:Many antiarrhythmic agents have adverse hemodynamic effects which limit their use in patients with impaired ventricular function or during tachyarrhythmias. Ibutilide is an intravenous, selective class III antiarrhythmic agent that is effective for conversion of atrial fibrillation or flutter. This multicenter, randomized, placebo-controlled, dose-ranging study evaluated the effects of intravenous Ibutilide on hemodynamic parameters during invasive monitoring in 47 patients with or without reduced left ventricular ejection fraction (LVEF) > 35% or < or = 35%. Patients received either placebo or Ibutilide as a 10-minute loading and a 30-minute maintenance infusion using 1 of the following dosing regimens: placebo then placebo (n = 12); 0.01 then 0.002 mg/kg (n = 12); 0.02 then 0.004 mg/kg (n = 12); or 0.03 then 0.006 mg/kg (n = 11). Ibutilide significantly increased QT and QTc intervals in a dose-related manner with mean increases ranging from 51 to 99 ms, but did not alter the PR interval or QRS duration. During Ibutilide infusion, a few small but statistically significant changes from baseline in several hemodynamic variables were present. However, the changes in cardiac output, pulmonary artery or capillary wedge pressures, blood pressure, or heart rate in patients receiving Ibutilide were not significantly different from the changes in patients receiving placebo. Thus, Ibutilide did not cause clinically important adverse hemodynamic effects, even in patients with depressed ventricular function. One patient developed 2 episodes of nonsustained torsades de pointes during Ibutilide. These results demonstrate that with careful monitoring for proarrhythmia, Ibutilide can be used safely from a hemodynamic standpoint in the acute treatment of arrhythmias, even in patients with reduced ventricular function.
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efficacy of intravenous Ibutilide for rapid termination of atrial fibrillation and atrial flutter a dose response study
Journal of the American College of Cardiology, 1996Co-Authors: Kenneth A Ellenbogen, Mark A. Wood, Bruce S Stambler, Kimberly T. Perry, Philip T Sager, Robert C Wesley, Marc D Meissner, Robert G Zoble, Linda K Wakefield, James T VanderlugttAbstract:Abstract Objectives. Currently available antiarrhythmic drugs have limited efficacy for short-term, rapid termination of atrial fibrillation and atrial flutter. Background. Ibutilide fumarate is an investigational class III antiarrhythmic agent that prolongs repolarization by increasing the slow inward sodium current and by blocking the delayed rectifier current. It can be administered intravenously and has a rapid onset of electrophysiologic effects. Methods. The efficacy and safety of Ibutilide were studied in 200 patients with atrial flutter >3 b in duration or atrial fibrillation 3 h to 90 days in duration. Patients were randomized to receive a single intravenous dose of placebo or an infusion of Ibutilide fumarate at 0.005, 0.010, 0.015, or 0.025 mg/kg body weight over 10 min. Conversion was defined as termination of the atrial arrhythmia during or within 60 min after infusion. Forty-one patients received placebo and 159 received Ibutilide (0.005 mg/kg [n = 41], 0.010 mg/kg [n = 40], 0.015 mg/kg [n = 38] or 0.025 mg/kg [n = 40]). Results. The arrhythmia terminated in 34% of drug-treated patients. The rates of successful arrhythmia termination were 3% for placebo and 12%, 33%, 45% and 46%, respectively, for 0.005-, 0.010-, 0.015- and 0.025-mg/kg Ibutilide. The placebo and 0.005-mg/kg Ibutilide groups had lower success rates than all other dose groups (p Conclusions. These data demonstrate that Ibutilide is able to rapidly terminate atrial fibrillation and atrial flutter.
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comparative efficacy of intravenous Ibutilide versus procainamide for enhancing termination of atrial flutter by atrial overdrive pacing
American Journal of Cardiology, 1996Co-Authors: Mark A. Wood, Bruce S Stambler, Kenneth A EllenbogenAbstract:This study compares the influence of intravenous Ibutilide, a class III antiarrhythmic agent, with procainamide, a class IA antiarrhythmic agent, and with placebo on its ability to terminate atrial flutter using rapid atrial pacing. Fifty-nine episodes of atrial flutter in 54 patients who failed to terminate with an intravenous infusion of Ibutilide, procainamide, or placebo alone underwent attempts at pacing termination using a standard protocol of burst atrial overdrive pacing. Atrial flutter cycle length and atrial monophasic action potential duration recorded from the right atrium during atrial flutter were measured at baseline and following infusion of Ibutilide, procainamide, or placebo. Both Ibutilide and procainamide significantly enhanced (p <0.001) pacing-induced termination of atrial flutter compared with placebo. Pacing converted 2 of 11 patients (18%) who received placebo, 13 of 15 patients (87%) who received Ibutilide, and 29 of 33 patients (88%) who received procainamide to sinus rhythm. Ibutilide and procainamide compared with placebo markedly reduced (p <0.001) the incidence of pacing-induced atrial fibrillation. The atrial flutter cycle length was prolonged significantly less (p <0.001), and the atrial monophasic action potential duration was increased significantly more (p <0.001) by Ibutilide than by procainamide. Although the electrophysiologic changes induced by these antiarrhythmic agents contributed to facilitating pacing-induced termination, neither tachycardia cycle length nor action potential duration were useful predictors of the ability of pacing to terminate atrial flutter. In conclusion, despite differing electrophysiologic effects, the use of intravenous Ibutilide or procainamide enhances the termination of atrial flutter by atrial overdrive pacing.
Bruce S Stambler - One of the best experts on this subject based on the ideXlab platform.
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Clinical and electrophysiologic effects of calcium channel blockers in patients receiving Ibutilide.
American heart journal, 2002Co-Authors: Mark A. Wood, Bruce S Stambler, David M. Gilligan, Chris Brown-mahoney, Fatemeh Nematzadeh, Kenneth A EllenbogenAbstract:Abstract Background Ibutilide is indicated for the acute termination of atrial fibrillation and atrial flutter. Recent work concludes that Ibutilide activates a late inward sodium current that is blocked by nifedipine. Because calcium channel blockers are commonly used in patients with atrial fibrillation, it is important to exclude an antagonistic effect on Ibutilide in the clinical setting. Methods We performed a retrospective electrocardiographic (ECG) review of patients enrolled in 3 clinical trials of Ibutilide (2 atrial fibrillation conversion protocols and 1 ventricular tachycardia suppression protocol) to determine clinical efficacy and ECG effects of Ibutilide in patients receiving and not receiving calcium channel blockers. Calcium channel blockers were administered as clinically indicated. A meta-analysis of the effects of calcium channel blockers on the conversion efficacy of atrial fibrillation and atrial flutter by Ibutilide was also performed for studies in the literature. Results One hundred thirty patients were included in the ECG analysis (106 from atrial fibrillation protocols and 24 from the ventricular tachycardia protocol). Sixty-eight of the 130 patients were taking calcium channel blockers at the time of Ibutilide administration. There were no differences in the QT or QTc intervals, conversion rate for atrial fibrillation or atrial flutter, or suppression of ventricular tachycardia between patients taking and not taking calcium channel blockers. In the meta-analysis of 4 studies, there was no difference in the conversion rates between patients taking (52%, n = 221) and not taking (45%, n = 402) calcium channel blockers ( P =.09). Conclusions In the clinical setting, the concomitant use of calcium channel blockers does not alter the ECG effects or efficacy of Ibutilide for the treatment of atrial or ventricular arrhythmias. (Am Heart J 2002;143:176-80.)
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Conversion efficacy and safety of intravenous Ibutilide compared with intravenous procainamide in patients with atrial flutter or fibrillation.
Journal of the American College of Cardiology, 1998Co-Authors: Annabelle S. Volgman, James T. Vanderlugt, Bruce S Stambler, Peter A. Carberry, William R. Lewis, George H. Dunn, Kimberly T. Perry, Peter R. KoweyAbstract:Objectives. This multicenter study compared the efficacy and safety of Ibutilide versus procainamide for conversion of recent-onset atrial flutter or fibrillation. Background. Ibutilide fumarate is an intravenous (IV) class III antiarrhythmic agent that has been shown to be significantly more effective than placebo in the pharmacologic conversion of atrial flutter and fibrillation to sinus rhythm. Procainamide is commonly used for conversion of recent-onset atrial fibrillation to normal sinus rhythm. Methods. One hundred twenty-seven patients (age range 22 to 92 years) with atrial flutter or fibrillation of 3 h to 90 days’ (mean 21 days) duration were randomized to receive either two 10-min IV infusions of 1 mg of Ibutilide fumarate, separated by a 10-min infusion of 5% dextrose in sterile water, or three successive 10-min IV infusions of 400 mg of procainamide hydrochloride. Results. Of the 127 patients, 120 were evaluated for efficacy: 35 (58.3%) of 60 in the Ibutilide group compared with 11 (18.3%) of 60 in the procainamide group had successful termination within 1.5 h of treatment (p < 0.0001). Seven patients were found to have violated the protocol and were not included in the final evaluation. In the patients with atrial flutter, Ibutilide had a significantly higher success rate than procainamide (76% [13 of 17] vs. 14% [3 of 22], p = 0.001). Similarly, in the atrial fibrillation group, Ibutilide had a significantly higher success rate than procainamide (51% [22 of 43] vs. 21% [8 of 38], p = 0.005). One patient who received Ibutilide, which was found to be a protocol violation, had sustained polymorphic ventricular tachycardia requiring direct current cardioversion. Seven patients who received procainamide became hypotensive. Conclusions. This study establishes the superior efficacy of Ibutilide over procainamide when administered to patients to convert either atrial fibrillation or atrial flutter to sinus rhythm. Hypotension was the major adverse effect seen with procainamide. A low incidence of serious proarrhythmia was seen with the administration of Ibutilide occurring at the end of infusion.
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antiarrhythmic actions of intravenous Ibutilide compared with procainamide during human atrial flutter and fibrillation electrophysiological determinants of enhanced conversion efficacy
Circulation, 1997Co-Authors: Bruce S Stambler, Mark A. Wood, Kenneth A EllenbogenAbstract:Background The selective class III antiarrhythmic agent Ibutilide prolongs action potential duration and terminates atrial flutter (AFL) and fibrillation (AF), but the mechanism of its antiarrhythmic efficacy in humans has not been fully characterized. This study compared the antiarrhythmic effects of Ibutilide with the class IA agent procainamide in humans during AFL and AF. Antiarrhythmic drug actions and electrophysiological characteristics of AFL and AF that enhanced pharmacological termination were investigated. Methods and Results Right atrial monophasic action potentials were recorded during 148 episodes of AFL (n=89) or AF (n=59) in 136 patients treated with intravenous Ibutilide (n=73) or placebo (n=22) as participants in randomized, double-blinded comparative studies or intravenous procainamide (n=53) in a concurrent open-label study. The conversion rates in AFL with Ibutilide, procainamide, and placebo were 64% (29 of 45 patients), 0% (0 of 33), and 0% (0 of 11), respectively, whereas in AF the rates were 32% (9 of 28), 5% (1 of 20), and 0% (0 of 11), respectively. In AFL, Ibutilide increased atrial monophasic action potential duration (MAPD) more (30% versus 18%, P <.001) and prolonged atrial cycle length (CL) less (16% versus 26%, P <.001) than procainamide. Ibutilide shortened and procainamide prolonged action potential diastolic interval during AFL (−12% versus 51%, P <.001). Ibutilide increased MAPD/CL ratio, whereas procainamide tended to decrease this ratio (13% versus −6%, P <.01). In AF, Ibutilide and procainamide induced similar increases in atrial CL (48% versus 45%), but Ibutilide induced a greater increase in MAPD (52% versus 37%, P <.05). Independent electrophysiological predictors of pharmacological arrhythmia termination were increase in MAPD/CL ratio ( P =.005) in AFL and longer baseline mean MAPD ( P =.011) in AF. Termination of AFL with Ibutilide was characterized by significant increases in beat-to-beat atrial CL, MAPD, and diastolic interval variability. Ibutilide was significantly more effective in converting AF when the mean atrial CL was ≥160 ms (64% versus 0%, P <.001) or MAPD was ≥125 ms (57% versus 0%, P =.002) at baseline. Conclusions Enhanced conversion efficacy of Ibutilide compared with procainamide in AFL is correlated with a relatively greater prolongation of atrial MAPD than atrial CL, and termination of AFL by Ibutilide is characterized by oscillations in atrial CL and MAPD. Conversion of AF by Ibutilide is enhanced by a longer baseline mean atrial CL or MAPD.
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Acute hemodynamic effects of intravenous Ibutilide in patients with or without reduced left ventricular function.
The American journal of cardiology, 1997Co-Authors: Bruce S Stambler, Kenneth A Ellenbogen, Karen J. Beckman, Alan H. Kadish, John Camm, Kim T. Perry, James T. VanderlugtAbstract:Many antiarrhythmic agents have adverse hemodynamic effects which limit their use in patients with impaired ventricular function or during tachyarrhythmias. Ibutilide is an intravenous, selective class III antiarrhythmic agent that is effective for conversion of atrial fibrillation or flutter. This multicenter, randomized, placebo-controlled, dose-ranging study evaluated the effects of intravenous Ibutilide on hemodynamic parameters during invasive monitoring in 47 patients with or without reduced left ventricular ejection fraction (LVEF) > 35% or < or = 35%. Patients received either placebo or Ibutilide as a 10-minute loading and a 30-minute maintenance infusion using 1 of the following dosing regimens: placebo then placebo (n = 12); 0.01 then 0.002 mg/kg (n = 12); 0.02 then 0.004 mg/kg (n = 12); or 0.03 then 0.006 mg/kg (n = 11). Ibutilide significantly increased QT and QTc intervals in a dose-related manner with mean increases ranging from 51 to 99 ms, but did not alter the PR interval or QRS duration. During Ibutilide infusion, a few small but statistically significant changes from baseline in several hemodynamic variables were present. However, the changes in cardiac output, pulmonary artery or capillary wedge pressures, blood pressure, or heart rate in patients receiving Ibutilide were not significantly different from the changes in patients receiving placebo. Thus, Ibutilide did not cause clinically important adverse hemodynamic effects, even in patients with depressed ventricular function. One patient developed 2 episodes of nonsustained torsades de pointes during Ibutilide. These results demonstrate that with careful monitoring for proarrhythmia, Ibutilide can be used safely from a hemodynamic standpoint in the acute treatment of arrhythmias, even in patients with reduced ventricular function.
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efficacy of intravenous Ibutilide for rapid termination of atrial fibrillation and atrial flutter a dose response study
Journal of the American College of Cardiology, 1996Co-Authors: Kenneth A Ellenbogen, Mark A. Wood, Bruce S Stambler, Kimberly T. Perry, Philip T Sager, Robert C Wesley, Marc D Meissner, Robert G Zoble, Linda K Wakefield, James T VanderlugttAbstract:Abstract Objectives. Currently available antiarrhythmic drugs have limited efficacy for short-term, rapid termination of atrial fibrillation and atrial flutter. Background. Ibutilide fumarate is an investigational class III antiarrhythmic agent that prolongs repolarization by increasing the slow inward sodium current and by blocking the delayed rectifier current. It can be administered intravenously and has a rapid onset of electrophysiologic effects. Methods. The efficacy and safety of Ibutilide were studied in 200 patients with atrial flutter >3 b in duration or atrial fibrillation 3 h to 90 days in duration. Patients were randomized to receive a single intravenous dose of placebo or an infusion of Ibutilide fumarate at 0.005, 0.010, 0.015, or 0.025 mg/kg body weight over 10 min. Conversion was defined as termination of the atrial arrhythmia during or within 60 min after infusion. Forty-one patients received placebo and 159 received Ibutilide (0.005 mg/kg [n = 41], 0.010 mg/kg [n = 40], 0.015 mg/kg [n = 38] or 0.025 mg/kg [n = 40]). Results. The arrhythmia terminated in 34% of drug-treated patients. The rates of successful arrhythmia termination were 3% for placebo and 12%, 33%, 45% and 46%, respectively, for 0.005-, 0.010-, 0.015- and 0.025-mg/kg Ibutilide. The placebo and 0.005-mg/kg Ibutilide groups had lower success rates than all other dose groups (p Conclusions. These data demonstrate that Ibutilide is able to rapidly terminate atrial fibrillation and atrial flutter.
Peter R. Kowey - One of the best experts on this subject based on the ideXlab platform.
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Conversion efficacy and safety of intravenous Ibutilide compared with intravenous procainamide in patients with atrial flutter or fibrillation.
Journal of the American College of Cardiology, 1998Co-Authors: Annabelle S. Volgman, James T. Vanderlugt, Bruce S Stambler, Peter A. Carberry, William R. Lewis, George H. Dunn, Kimberly T. Perry, Peter R. KoweyAbstract:Objectives. This multicenter study compared the efficacy and safety of Ibutilide versus procainamide for conversion of recent-onset atrial flutter or fibrillation. Background. Ibutilide fumarate is an intravenous (IV) class III antiarrhythmic agent that has been shown to be significantly more effective than placebo in the pharmacologic conversion of atrial flutter and fibrillation to sinus rhythm. Procainamide is commonly used for conversion of recent-onset atrial fibrillation to normal sinus rhythm. Methods. One hundred twenty-seven patients (age range 22 to 92 years) with atrial flutter or fibrillation of 3 h to 90 days’ (mean 21 days) duration were randomized to receive either two 10-min IV infusions of 1 mg of Ibutilide fumarate, separated by a 10-min infusion of 5% dextrose in sterile water, or three successive 10-min IV infusions of 400 mg of procainamide hydrochloride. Results. Of the 127 patients, 120 were evaluated for efficacy: 35 (58.3%) of 60 in the Ibutilide group compared with 11 (18.3%) of 60 in the procainamide group had successful termination within 1.5 h of treatment (p < 0.0001). Seven patients were found to have violated the protocol and were not included in the final evaluation. In the patients with atrial flutter, Ibutilide had a significantly higher success rate than procainamide (76% [13 of 17] vs. 14% [3 of 22], p = 0.001). Similarly, in the atrial fibrillation group, Ibutilide had a significantly higher success rate than procainamide (51% [22 of 43] vs. 21% [8 of 38], p = 0.005). One patient who received Ibutilide, which was found to be a protocol violation, had sustained polymorphic ventricular tachycardia requiring direct current cardioversion. Seven patients who received procainamide became hypotensive. Conclusions. This study establishes the superior efficacy of Ibutilide over procainamide when administered to patients to convert either atrial fibrillation or atrial flutter to sinus rhythm. Hypotension was the major adverse effect seen with procainamide. A low incidence of serious proarrhythmia was seen with the administration of Ibutilide occurring at the end of infusion.
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safety and risk benefit analysis of Ibutilide for acute conversion of atrial fibrillation flutter
American Journal of Cardiology, 1996Co-Authors: Peter R. Kowey, James T. Vanderlugt, John R. LudererAbstract:Safety data were reviewed from several controlled clinical trials of Ibutilide, a new class III antiarrhythmic drug recently approved for the acute interruption of atrial fibrillation and flutter. Noncardiovascular adverse effects of Ibutilide were similar in frequency to those with placebo. Cardiovascular adverse effects occurred in 24.9% of 586 Ibutilide-treated patients as compared with 22.2% of 108 sotalol-treated patients, and 7.1% of 127 patients who received placebo. Polymorphous ventricular tachycardia, diagnosed as torsades de pointes, was more common with Ibutilide than with placebo or sotalol treatment. It occurred in 4.3% of patients, including 1.7% whose torsades de pointes was sustained and required cardioversion. In the Ibutilide group, 4.9% of patients had nonsustained monomorphic ventricular tachycardia compared with 3.7% of patients who received sotalol and 0.8% of patients who received placebo. All of the sustained arrhythmias except 1 occurred within 1 hour of the end of Ibutilide infusion, and all were successfully terminated without sequelae. In a multiple logistic regression analysis, bradycardia, low body weight, and history of congestive heart failure were predictive of the occurrence of torsades de pointes. Hypotension, conduction block, bradycardia, and all other cardiovascular adverse effects all occurred at similar rates in the Ibutilide- and placebo-treated groups. For patients who failed to convert while receiving Ibutilide, there was no decrease in the efficiency of cardioversion, nor was there an increase in the mean energy requirements for subsequent electrical cardioversion. Analysis of a 3-month follow-up study showed that patients receiving Ibutilide had similar outcomes compared with patients receiving placebo. One placebo-treated patient died. Other than torsades de pointes, Ibutilide has a very good safety profile. Under the proper clinical conditions, this complication of Ibutilide therapy can be rapidly diagnosed and effectively treated.
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Safety and Risk/Benefit Analysis of Ibutilide for Acute Conversion of Atrial Fibrillation/Flutter
The American Journal of Cardiology, 1996Co-Authors: Peter R. Kowey, James T. Vanderlugt, John R. LudererAbstract:Safety data were reviewed from several controlled clinical trials of Ibutilide, a new class III antiarrhythmic drug recently approved for the acute interruption of atrial fibrillation and flutter. Noncardiovascular adverse effects of Ibutilide were similar in frequency to those with placebo. Cardiovascular adverse effects occurred in 24.9% of 586 Ibutilide-treated patients as compared with 22.2% of 108 sotalol-treated patients, and 7.1% of 127 patients who received placebo. Polymorphous ventricular tachycardia, diagnosed as torsades de pointes, was more common with Ibutilide than with placebo or sotalol treatment. It occurred in 4.3% of patients, including 1.7% whose torsades de pointes was sustained and required cardioversion. In the Ibutilide group, 4.9% of patients had nonsustained monomorphic ventricular tachycardia compared with 3.7% of patients who received sotalol and 0.8% of patients who received placebo. All of the sustained arrhythmias except 1 occurred within 1 hour of the end of Ibutilide infusion, and all were successfully terminated without sequelae. In a multiple logistic regression analysis, bradycardia, low body weight, and history of congestive heart failure were predictive of the occurrence of torsades de pointes. Hypotension, conduction block, bradycardia, and all other cardiovascular adverse effects all occurred at similar rates in the Ibutilide- and placebo-treated groups. For patients who failed to convert while receiving Ibutilide, there was no decrease in the efficiency of cardioversion, nor was there an increase in the mean energy requirements for subsequent electrical cardioversion. Analysis of a 3-month follow-up study showed that patients receiving Ibutilide had similar outcomes compared with patients receiving placebo. One placebo-treated patient died. Other than torsades de pointes, Ibutilide has a very good safety profile. Under the proper clinical conditions, this complication of Ibutilide therapy can be rapidly diagnosed and effectively treated.