Symptoms at the Time of Arrhythmia Recurrence in Patients
Background: Azimilide is a new antiarrhythmic agent being developed for the management for atrial fibrillation and flutter (AF). Four randomized, placebo-controlled, double-blind trials have been performed that investigated the effect of azimilide on time to first recurrence of symptomatic AF. This paper examines the data collected during those studies regarding the symptoms reported by patients at the time of AF recurrence.
Methods: At the time that patients reported their first documented symptomatic recurrence of arrhythmia, they were systematically asked whether or not they were experiencing any of the following 6 symptoms: palpitation, fatigue, chest pain, shortness of breath, dizziness, or sweating. Patients were required to answer yes or no. A symptom score was created varying from 0 to 6, in increasing order of number of symptoms reported. This was compared for patients receiving either of 2 doses of azimilide or placebo. The relationship between the number of symptoms, heart rate at time of arrhythmia recurrence and treatment was analyzed.
Results: In 2 separate studies, azimilide at a dose of 125 mg/day significantly reduced the number of symptoms at the time of arrhythmia recurrence compared to placebo. On the other hand, in 2 studies, the dose of 100 mg/day did not significantly reduce symptom burden. The individual symptoms significantly reduced by azimilide125 mg/day were fatigue, shortness of breath, chest pain and dizziness. Palpitations and sweating were not significantly reduced. Modeling of heart rate at the time of arrhythmia recurrence, symptoms and treatment indicated that a small reduction in heart rate with azimilide accounted for only a small part of the symptom reduction. There was another effect of azimilide: an average reduction of 0.38 symptoms (P < .01) that was independent of heart rate.
Conclusion: Azimilide (125 mg/day) reduces the number of symptoms reported at the time of AF recurrence.
Azimilide is a new antiarrhythmic agent that is being developed for the control of atrial fibrillation and flutter (AF). It is a Vaughan-Williams Class III agent that lengthens action potential duration without affecting Phase 0. On the basis of promising preclinical studies, a series of double-blind, placebo-controlled, randomized trials were performed to evaluate the efficacy of a range of doses of azimilide against recurrence of arrhythmia in patients with AF and with supraventricular tachycardia. These trials have been completed and reported. The main findings are that doses of azimilide of 100 mg/day and 125 mg/day significantly increase the time to symptomatic AF recurrence in these patients, and doses below this do not have a significant effect.
The paradigm for the design of most recent trials evaluating treatments to control arrhythmia recurrence in patients with AF has been measurement and modeling of time to first recurrence. This approach is efficient and practical but it neglects several important aspects in the clinical management of these patients. Most patients are relatively unconcerned about the time to first recurrence. Their concerns include the overall frequency of AF attacks, the duration of those attacks and the accompanying symptoms. Thus it is important to consider these other aspects of symptoms related to AF.
During the 4 completed double-blind, placebo-controlled trials of azimilide, presence of symptoms was assessed systematically at the time of arrhythmia recurrence. The purpose of this paper is to present our analysis of these data.
Background: Azimilide is a new antiarrhythmic agent being developed for the management for atrial fibrillation and flutter (AF). Four randomized, placebo-controlled, double-blind trials have been performed that investigated the effect of azimilide on time to first recurrence of symptomatic AF. This paper examines the data collected during those studies regarding the symptoms reported by patients at the time of AF recurrence.
Methods: At the time that patients reported their first documented symptomatic recurrence of arrhythmia, they were systematically asked whether or not they were experiencing any of the following 6 symptoms: palpitation, fatigue, chest pain, shortness of breath, dizziness, or sweating. Patients were required to answer yes or no. A symptom score was created varying from 0 to 6, in increasing order of number of symptoms reported. This was compared for patients receiving either of 2 doses of azimilide or placebo. The relationship between the number of symptoms, heart rate at time of arrhythmia recurrence and treatment was analyzed.
Results: In 2 separate studies, azimilide at a dose of 125 mg/day significantly reduced the number of symptoms at the time of arrhythmia recurrence compared to placebo. On the other hand, in 2 studies, the dose of 100 mg/day did not significantly reduce symptom burden. The individual symptoms significantly reduced by azimilide125 mg/day were fatigue, shortness of breath, chest pain and dizziness. Palpitations and sweating were not significantly reduced. Modeling of heart rate at the time of arrhythmia recurrence, symptoms and treatment indicated that a small reduction in heart rate with azimilide accounted for only a small part of the symptom reduction. There was another effect of azimilide: an average reduction of 0.38 symptoms (P < .01) that was independent of heart rate.
Conclusion: Azimilide (125 mg/day) reduces the number of symptoms reported at the time of AF recurrence.
Azimilide is a new antiarrhythmic agent that is being developed for the control of atrial fibrillation and flutter (AF). It is a Vaughan-Williams Class III agent that lengthens action potential duration without affecting Phase 0. On the basis of promising preclinical studies, a series of double-blind, placebo-controlled, randomized trials were performed to evaluate the efficacy of a range of doses of azimilide against recurrence of arrhythmia in patients with AF and with supraventricular tachycardia. These trials have been completed and reported. The main findings are that doses of azimilide of 100 mg/day and 125 mg/day significantly increase the time to symptomatic AF recurrence in these patients, and doses below this do not have a significant effect.
The paradigm for the design of most recent trials evaluating treatments to control arrhythmia recurrence in patients with AF has been measurement and modeling of time to first recurrence. This approach is efficient and practical but it neglects several important aspects in the clinical management of these patients. Most patients are relatively unconcerned about the time to first recurrence. Their concerns include the overall frequency of AF attacks, the duration of those attacks and the accompanying symptoms. Thus it is important to consider these other aspects of symptoms related to AF.
During the 4 completed double-blind, placebo-controlled trials of azimilide, presence of symptoms was assessed systematically at the time of arrhythmia recurrence. The purpose of this paper is to present our analysis of these data.