45
48
At 24 hours†
2
12
28
42
43
Atrial flutter
Initially*
0
14
30
58
55
At 24 hours†
0
14
30
58
50
Atrial Fibrillation
Initially*
5
10
35
32
40
At 24 hours†
5
10
25
26
35
PERCENT OF PATIENTS WHO CONVERTED (Second Trial)
Ibutilide
Placebo 1.0 mg/0.5 mg 1.0 mg/1.0 mg
n 86 86 94
* Percent of patients who converted within 90 minutes after the start of infusion. † Percent of patients who remained in sinus rhythm 24 hours after dosing.
Both
Initially*
2
43
44
At 24 hours†
2
34
37
Atrial flutter
Initially*
2
48
63
At 24 hours†
2
45
59
Atrial Fibrillation
Initially*
2
38
25
At 24 hours†
2
21
17
The numbers of patients who remained in the converted rhythm at the end of 24 hours were slightly less than those patients who converted initially, but the difference between conversion rates for ibutilide compared to placebo was still statistically significant. In long-term follow-up, approximately 40% of all patients remained recurrence free, usually with chronic prophylactic treatment, 400 to 500 days after acute treatment, regardless of the method of conversion.
Patients with more recent onset of arrhythmia had a higher rate of conversion. Response rates were 42% and 50% for patients with onset of atrial fibrillation/flutter for less than 30 days in the two efficacy studies compared to 16% and 31% in those with more chronic arrhythmias.
Ibutilide was equally effective in patients below and above 65 years of age and in men and women. Female patients constituted about 20% of patients in controlled studies.
Post-cardiac Surgery
In a double-blind, parallel group study, 302 patients with atrial fibrillation (n=201) or atrial flutter (n=101) that occurred 1 to 7 days after coronary artery bypass graft or valvular surgery and lasted 1 hour to 3 days were randomized to receive two 10-minute infusions of placebo, or 0.25, 0.5 or 1 mg of ibutilide fumarate. Among patients with atrial flutter, conversion rates at 1.5 hours were: placebo, 4%; 0.25 mg ibutilide fumarate, 56%; 0.5 mg ibutilide fumarate, 61%; and 1 mg ibutilide fumarate, 78%. Among patients with atrial fibrillation, conversion rates at 1.5 hours were: placebo, 20%; 0.25 mg ibutilide fumarate, 28%; 0.5 mg ibutilide fumarate, 42%, and 1 mg ibutilide fumarate, 44%. The majority of patients (53% and 72% in the 0.5 mg and 1 mg dose groups, respectively) converted to sinus rhythm remained in sinus rhythm for 24 hours. Patients were not given other antiarrhythmic drugs within 24 hours of ibutilide fumarate infusion in this study.
INDICATIONS AND USAGE
Ibutilide fumarate injection is indicated for the rapid conversion of atrial fibrillation or atrial flutter of recent onset to sinus rhythm. Patients with atrial arrhythmias of longer duration are less likely to respond to ibutilide fumarate injection. The effectiveness of ibutilide has not been determined in patients with arrhythmias of more than 90 days in duration.
CONTRAINDICATIONS
Ibutilide fumarate injection is contraindicated in patients who have previously demonstrated hypersensitivity to ibutilide fumarate or any of the other product componen
