Role of Ibutilide in Atrial Fibrillation Cardioversion
Abstract & commentary
Synopsis: Ibutilide enhances the efficacy of transthoracic cardioversion among patients with atrial fibrillation.
Source: Oral H, et al. N Engl J Med 1999;340: 1849-1854.
Oral and colleagues at the university of Michigan evaluated the potential ability of ibutilide to facilitate cardioversion in patients with atrial fibrillation. They enrolled 100 consecutive patients referred for elective cardioversion. Fifty patients were randomly assigned to undergo transthoracic cardioversion without ibutilide pretreatment, whereas the other 50 patients underwent transthoracic cardioversion after an infusion of 1 mg of ibutilide. The 50 patients in the two groups were well matched with regard to age, gender, body size, etiology of heart disease, and duration of atrial fibrillation. There were slightly more patients on either amiodarone or a class I antiarrhythmic agent in the control group compared to the ibutilide pretreatment group (29 vs 21). Drug administration was not placebo controlled and not double blind. Only 1 mg of ibutilide rather than the usually recommended dose of two 1-mg infusions was used. Cardioversion was performed after fentanyl and midazolam sedation using adhesive 12-cm patch electrodes. A step-up atrial defibrillation testing protocol was used for cardioversion that used shocks of 50, 100, 200, 300, and 360 joules.
Among the 50 patients who were given ibutilide before the initial cardioversion attempt, 10 had restoration of sinus rhythm on ibutilide alone and the remaining 40 were all restored to sinus rhythm by transthoracic DC shock. The mean energy requirement in the patients who underwent shock was 160 ± 80 joules. Among the 50 patients who did not receive ibutilide pretreatment, 36 were converted with a mean energy of 228 ± 93 joules, whereas 14 remained in atrial fibrillation. These patients then received 1 mg of ibutilide and underwent a second cardioversion attempt. All 14 were then restored to sinus rhythm. There was a trend toward a greater success rate with ibutilide alone in patients with shorter duration of atrial fibrillation (24 ± 43 vs 122 ± 179 days) but this trend did not reach statistical significance. There were no significant differences between the two groups of patients with regard to age, weight, type or presence of structural heart disease, concurrent drug therapy, left atrial size, or left ventricular ejection fraction.
Proarrhythmia was noted in three patients who received ibutilide. Two of 64 patients developed sustained polymorphic ventricular tachycardia and required a transthoracic cardioversion. Both of these patients had ejection fractions below 30%. Neither was on another antiarrhythmic drug that prolongs the QT interval. A third patient, whose ejection fraction is not reported, had a single episode of polymorphic ventricular tachycardia 10 minutes after the completion of the ibutilide infusion. As expected, the QT interval was significantly prolonged by ibutilide infusion. No other electrocardiographic changes were noted.
When the recurrence of atrial fibrillation was analyzed, there was no difference between the two groups. Fifty-seven percent of patients who were randomly assigned to transthoracic cardioversion alone were free of recurrent arrhythmias at the six-month follow-up point as compared to 64% of patients who received ibutilide. Age, duration of atrial fibrillation, presence of structural heart disease, concomitant drug therapy, left atrial size, and left atrial ejection fraction did not predict recurrence of atrial fibrillation.
Oral et al conclude that ibutilide enhances the efficacy of transthoracic cardioversion among patients with atrial fibrillation. They, however, suggest that the drug should be restricted to patients with good ejection fractions due to the occurrence of proarrhythmia in two low ejection fraction patients in this series.
Comment by John P. DiMarco, MD, PhD
Ibutilide is a relatively new antiarrhythmic drug that is available for conversion of episodes of atrial fibrillation and atrial flutter. The recommended dose is 1 mg intravenously followed by a 10-minute observation period and then a second mg if cardioversion has not occurred. The drug by itself has a reasonable success rate in patients with atrial flutter and a modest success rate (20-40%) among patients with atrial fibrillation. This paper illustrates that ibutilide may have a greater value in facilitating a cardioversion rather than being used as the only therapy. Several features in this report, however, deserve comment.
The study was apparently performed in an open label fashion without placebo control. It should have been relatively easy to provide placebo in this study. Although conversion to sinus rhythm should be an objective end point, one wonders why Oral et al didn’t use a double-blind, controlled protocol. As Oral et al also mention, it should be noted that 14 of the patients in this group of 100 had been referred for possible intra-atrial cardioversion. This probably accounts for a high proportion of cardioversion failures in the control group. However, the fact that all of the patients treated with ibutilide were converted with the initial sequence of shocks after receiving the drug is impressive. Unfortunately, this reviewer’s own experience has included several patients who failed to convert even after ibutilide infusion and the multicenter trials on ibutilide also included cardioversion failures.
The fact that three of 64 patients who received ibutilide developed polymorphic ventricular tachycardia is in agreement with data from the clinical studies. Oral et al argue that this occurs only in low ejection fraction patients. This may be correct but the statement cannot be supported on this limited amount of data. However, it would be prudent to be particularly cautious in patients with low ejection fractions until further experience has been obtained.
Other class III antiarrhythmic drugs seem to have beneficial effects on defibrillation threshold. Only six patients in this study were being treated with sotalol. Even though no adverse events occurred in these patients, I believe caution should be used in combining a drug such as ibutilide with sotalol, a drug that produces both bradycardia and QT prolongation.
These data are of great interest. Based on this study, I think a reasonable protocol would be to attempt two or three transthoracic shocks first. If the patient does not convert, ibutilide could be administered and another series of shocks administered during the same visit to the laboratory. The sequential use of ibutilide in this fashion would minimize the costs, the risk of proarrhythmia, and the need for prolonged monitoring in most patients.
The best use of ibutilide in patients with atrial tachyarrhythmias is:
a. pharmacologic cardioversion in heart failure patients.
b. to enhance electrical cardioversion.
c. to prevent proarrhythmia during DC shock.
d. for pharmacologic cardioversion.
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