Ibutilide Fumarate for the Conversion of Atrial Arrhythmias After Cardiac Surgery - Ibutilide Fumarate for the Conversion of Atrial Arrhythmias After Cardiac Surgery

Jan 27, 2005
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Date Published:
01/01/1999
Date Updated:
01/27/2005
Original Posted Date:
01/27/2005
References

Description:

The goal of this double-blind, placebo-controlled, randomized study was to evaluate the safety and efficacy of ibutilide in conversion of atrial arrhythmias among patients following cardiac surgery.

Hypothesis:

Ibutilide may be both safe and efficacious in converting atrial arrhythmias among postoperative cardiac surgery patients.

Study Design

Study Design:

Patients Enrolled: 302
Mean Follow Up: 72 hours
Female: 24
Mean Ejection Fraction: 49% had a normal ejection fraction; 31% had an ejection fraction <40%.

Patient Populations:

  • 18 years or older
  • Weight <300 pounds
  • Males or postmenopausal/surgically sterile females
  • Atrial fibrillation or atrial flutter persisting longer than one hour and less than three days following coronary artery or cardiac valvular surgery
  • Sinus rhythm at the time of surgery
  • Corrected QT interval ≤440 ms

Exclusions:

  • Prior exposure to ibutilide
  • History of torsades de pointes
  • Hemodynamic instability
  • Congestive heart failure
  • Heart rate <60 bpm
  • Myocardial infarction within 30 days
  • Severe hepatic impairment, hyperthyroidism, or electrolyte abnormality
  • Treatment with pressor drugs other than low-dose dopamine or dobutamine
  • Treatment with any class I or III antiarrhythmic drug within five half-lives of enrollment

Primary Endpoints:

Conversion of the atrial arrhythmia to sinus rhythm for any period of time within 90 minutes after initiating ibutilide or placebo infusion

Secondary Endpoints:

Cardiovascular adverse events included hypotension, QT prolongation, brady- or tachyarrhythmias, or congestive heart failure. Noncardiovascular adverse events included nausea, constipation, vomiting, fever, and diaphoresis. Adverse events were monitored for 72 hours after initial infusion.

Drug/Procedures Used:

  • Placebo
  • 0.25 mg of ibutilide fumarate
  • 0.50 mg of ibutilide fumarate
  • 1.0 mg of ibutilide fumarate
The dose was repeated if unsuccessful after 10 minutes. Those weighing less than 60 kg were randomized to placebo, 0.0025, 0.005, or 0.01 mg/kg.

Principal Findings:

  • Ibutilide at 0.25, 0.5, and 1.0 mg was associated with conversion to sinus rhythm at 90 minutes of 40%, 47%, and 57% compared to a 15% conversion rate in the placebo group (p=0.0001).
  • Those with atrial flutter had higher rates of conversion compared to those with atrial fibrillation (78% vs. 44% in the 1 mg group).
  • Higher doses of ibutilide were more often associated with lower time to conversion (23, 33, and 36 minutes for the 1, 0.5, and 0.25 mg ibutilide groups, respectively).
  • Polymorphic ventricular tachycardia occurred in 2.3% and 1.2% of the ibutilide-treated patients and placebo group, respectively.
  • Of those converted to sinus rhythm, 63% of those in the ibutilide-treated groups and 62% of those in the placebo group remained in sinus rhythm for 24 hours.
  • There was no significant difference in noncardiovascular adverse events.
  • There was a reduction in heart rate of 1.5 bpm and 15.4 bpm in the placebo and 1 mg ibutilide groups, respectively (p<0.05).
  • Polymorphic ventricular tachcardia was more common (2.3% vs. 1.2% in the ibutilide and placebo groups, respectively).

Interpretation:

Among patients who develop atrial fibrillation or atrial flutter following cardiac surgery, ibutilide treatment was associated with a higher rate of conversion to sinus rhythm and with increased rates of polymorphic ventricular tachycardia within 72 hours.

References:

VanderLugt JT, Mattioni T, Denker S, et al. Efficacy and safety of ibutilide fumarate for the conversion of atrial arrhythmias after cardiac surgery. Circulation 1999;100:369-75.

Keywords: Tachycardia, Ventricular, Cardiac Surgical Procedures, Heart Rate, Atrial Flutter, Sulfonamides


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