al infarction, and angina were excluded. About two thirds had cardiovascular symptoms, and the majority of patients had left atrial enlargement, decreased left ventricular ejection fraction, a history of valvular disease, or previous history of atrial fibrillation or flutter. Electrical cardioversion was allowed 90 minutes after the infusion was complete. Patients could be given other antiarrhythmic drugs 4 hours postinfusion.
Results of the first two studies are shown in the tables below. Conversion of atrial flutter/ fibrillation usually (70% of those who converted) occurred within 30 minutes of the start of infusion and was dose related. The latest conversion seen was at 90 minutes after the start of the infusion. Most converted patients remained in normal sinus rhythm for 24 hours. Overall responses in these patients, defined as termination of arrhythmias for any length of time during or within 1 hour following completed infusion of randomized dose, were in the range of 43% to 48% at doses above 0.0125 mg/kg (vs 2% for placebo). Twenty-four hour responses were similar. For these atrial arrhythmias, ibutilide was more effective in patients with flutter than fibrillation ( ≥ 48% vs ≤ 40%).
PERCENT OF PATIENTS WHO CONVERTED (First Trial)
Ibutilide
Placebo 0.005 mg/kg 0.01 mg/kg 0.015 mg/kg 0.025 mg/kg
n 41 41 40 38 40
* Percent of patients who converted within 70 minutes after the start of infusion. † Percent of patients who remained in sinus rhythm 24 hours after dosing.
Both Initially* 2 12 33 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 i |
