Antiarrhythmic Actions of Intravenous Ibutilide Compared With Procainamide During Human Atrial Flutter and Fibrillation: Electrophysiological Determinants of Enhanced Conversion Efficacy
Abstract
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 > or = 160 ms (64% versus 0%, P<.001) or MAPD was > or = 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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Dofetilide and ibutilide, pure class III AADs, are very effective for interrupting AFL intravenously, while class Ia and Ic drugs have little or no effect.
“Dofetilide and ibutilide, pure class III AADs, are very effective for interrupting AFL in intravenous administration, while Class Ia and Ic drugs have little or no effect.138 -142,149”
From European Heart Rhythm Association (EHRA) consensus document on the management of supraventricular arrhythmias, endorsed by Heart Rhythm Society (HRS), Asia-Pacific Heart Rhythm Society (APHRS), and Sociedad Latinoamericana de Estimulacion Cardiaca y Electrofisiologia (SOLAECE) (2017) · cites this paper as [140]
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- Authors
- Stambler, B. S., Wood, M. A., & Ellenbogen, K. A.
- Affiliations
- Harvard University (US)
- Venue
- Circulation
- Published
- 1997-12-16
- Volume
- 96
- Issue
- 12
- Pages
- 4298-4306
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2060841225
- Cited by
- 156
- References
- 35
- Citations by year
- 2025: 3 · 2024: 3 · 2023: 4 · 2022: 1 · 2020: 3 · 2019: 2 · 2018: 1 · 2017: 2 · 2016: 4 · 2015: 1 · 2014: 1 · 2013: 4 · 2012: 6
- FWCI
- 6.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Arrhythmias and Treatments
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Keywords
- ibutilide, procainamide, atrial flutter, atrial fibrillation, antiarrhythmic drugs, class III antiarrhythmic agents, monophasic action potential duration, atrial cycle length, intravenous administration
- MeSH terms
- Adult, Aged, Aged, 80 and over, Anti-Arrhythmia Agents, Atrial Fibrillation, Atrial Flutter, Electrophysiology, Female, Humans, Injections, Intravenous, Male, Middle Aged, Procainamide, Sulfonamides, Treatment Outcome
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