Ibutilide for the Conversion of Atrial Arrhythmias
abstract & commentary
Synopsis: Ibutilide is a useful treatment alternative for the conversion of atrial arrhythmias that occur after cardiac surgery.
Source: VanderLugt JT, et al. Circulation 1999;100: 369-375.
This double-blind, placebo-controlled, multicenter study was designed to assess the efficacy of ibutilide fumarate for the conversion of atrial flutter and atrial fibrillation in the early postoperative period after cardiac surgery. Patients were eligible for the study if they had atrial fibrillation or atrial flutter of longer than one hour and less than three days duration within 1-7 days of a cardiac surgical procedure for coronary or valvular heart disease. Patients were required to be hemodynamically stable and free of heart failure or angina at the time of enrollment. Patients with heart rates of less than 60 bpm were not eligible for inclusion. Patients were randomized to receive 10-minute intravenous infusions of either placebo or 0.25, 0.5, or 1.0 mg of ibutilide. There was a downward dosage adjustment for patients who weighed less than 60 kg. Patient were observed for 10 minutes after the end of the first infusion and, if they did not convert to sinus rhythm or suffer an adverse effect, a second infusion of the original dose over 10 minutes was repeated. The infusion was discontinued at the time of arrhythmia termination if there was hypotension, an increase in the QTc to greater than 600 msec, or the appearance of new ventricular arrhythmias. Patients were then observed off other antiarrhythmic drugs for 24 hours to determine the duration of maintenance of sinus rhythm. The prespecified end point for the trial was conversion of the atrial arrhythmia for any period within 90 minutes after the start of the first infusion.
A total of 302 patients were randomized. Of these, 76% were male, 201 had atrial fibrillation, and 101 had atrial flutter. The surgical procedures included coronary artery surgery alone in 69%, valvular surgery alone in 20%, and combined valve and coronary surgery in 11%. Thirty-one percent of the patients had an ejection fraction of less than 40%. By 90 minutes after the start of the first infusion, 13 of 84 (15%) placebo-treated patients and 41%, 47%, and 58% of the low, intermediate, and high-dose ibutilide groups converted to sinus rhythm. Patients with atrial flutter were more likely to convert with ibutilide compared to those with atrial fibrillation. Conversion was also more common among patients with coronary artery bypass grafting than it was among those with valvular surgery. The mean time to conversion was between 36 minutes for the 0.25-mg group and 23 minutes for the 1-mg group. Of the 104 patients successfully converted with ibutilide, 65 (63%) remained in sinus rhythm for 24 hours. Ibutilide prolonged the QT and QTc intervals, but prolongation of the QTc did not predict those who were to convert. The success rate was not statistically different between patient groups based on ejection fraction or treatment with beta adrenergic or calcium channel blocking agents. There was a trend toward increased benefit in patients treated with digoxin; 65% of digoxin-treated patients vs. 31% of patients not treated with digoxin who received 1 mg of ibutilide converted to sinus rhythm.
Noncardiovascular adverse events were uncommon with frequencies that did not differ between the placebo and ibutilide groups. Ibutilide did not have a significant effect on blood pressure. There were more ventricular arrhythmias in patients treated with ibutilide. Arrhythmias observed included ventricular premature depolarizations, nonsustained monomorphic or polymorphic ventricular tachycardia, and sustained ventricular tachycardia. Three patients who received ibutilide developed nonsustained polymorphic ventricular tachycardia and two had sustained polymorphic ventricular tachycardia, for an overall incidence of 2.3%. There was also one case of polymorphic ventricular tachycardia in the placebo group, but this occurred 27 hours after the initial infusion during treatment with procainamide. All sustained arrhythmias were successfully treated with cardioversion, magnesium, and/or pacing.
VanderLugt and associates conclude that ibutilide is a useful treatment alternative for the conversion of atrial arrhythmias that occur after cardiac surgery.
Comment by John P. DiMarco, MD, PhD
Atrial fibrillation and atrial flutter are common complications of cardiac surgery, both for coronary artery disease and valvular heart disease. Although rarely life-threatening, these arrhythmias may markedly slow the process of recuperation after the procedure and can significantly prolong hospital stay. In the absence of heart failure or preprocedure atrial arrhythmias, the duration of postoperative atrial arrhythmias usually is self-limited. The peak time for occurrence is between day two and day eight after cardiac surgery, with resolution within 30 days after the surgical procedure.
Management of atrial arrhythmias after cardiac surgery is often a significant clinical problem. If the ventricular rate can be controlled and the patient is asymptomatic, it is often better just to treat with AV nodal blocking agents, anticoagulation, and time. Many of the patients will have resolved the atrial fibrillation within two or three weeks after the surgery and no specific further drug therapy will be needed. If the atrial arrhythmia is associated with persistent symptoms that delay or preclude discharge, a cardioversion strategy is usually used. Since atrial fibrillation may recur, repeated transthoracic electrical cardioversion is not a particularly attractive option. Pharmacologic conversion is therefore attractive if it can be accomplished safely. Use of ibutilide has the advantage that the drug may be used on more than one occasion if atrial fibrillation recurs over a period of several days. Pharmacologic conversion does not require anesthesia or sedation for an electrical cardioversion.
As shown in this paper, an ibutilide infusion has a reasonably high rate of efficacy, particularly for atrial flutter, which is the more difficult arrhythmia to manage, and an acceptable rate of complications. However, use of ibutilide does require careful monitoring and I would recommend it be used only in a closely monitored setting—either a procedure room or an intensive care unit, where continuous observation of changes in rhythm can be maintained.
Many cardiologists prefer a prophylactic approach to the problem of atrial arrhythmias after cardiac surgery. Beta adrenergic blockers have been shown to be effective and some recent studies have shown efficacy with oral or intravenous amiodarone. However, atrial arrhythmias still occur and cardioversion is often necessary. Either intravenous ibutilide, as used in this paper, or oral propafenone, if ventricular function is normal and revascularization was complete, is probably the drug of choice.
Postcardiac surgery, the IV infusion of ibutilide for atrial flutter, or fibrillation results in:
a. successful cardioversion about half the time.
b. a higher conversion rate in flutter.
c. a higher conversion rate after bypass vs. valve surgery.
d. All of the above
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