Cardiovascular Drugs and Therapy 4: 573-578, 1990 © Kluwer Academic Publishers, Boston. Printed in U.S.A.
Efficacy of Encainide in Supraventricular Arrhythmias P e t e r E. Pool university of California, san DiegoSchool of Medicine; North County CardiologyResearchLaboratory, Encinitas, CA, USA
Summary. This review summarizes the data from all the studies conducted in the United States and Europe that have evaluated the efficacy of encainide in patients with a variety of supraventricular arrhythmias. Using clinical criteria of efficacy, encainide was found to be effective or partially effective in 77% of patients evaluated by electrophysiologic means. Similar levels of efficacy were observed in patients with AV as well as A V nodal reentry arrhythmias. Patients with other forms of supraventricular arrhythmias in smaller series also experienced comparable degrees of efficacy. Encainide was discontinued because of intolerance by 8% of the patients in these studies: 6% because of side effects and 2% because of proarrhythmia.
Key Words. encainide, supraventricular arrhythmias, atrial flutter/fibrillation, A V nodal reentry tachycardia, AV reentry tachycardia, electrophysiology, quinidine
Encainide is a Class IC antiarrhythmic agent that results in a marked slowing of intracardiac conduction with only minimal effects on repolarization. It has been shown to be effective for the therapy of ventricular as well as supraventricular arrhythmias. The following is a review of data (on file at Bristol-Myers) from all the studies that have been conducted in the United States and Europe to evaluate encainide for the control of supraventricular arrhythmias (SVT). Many of the patients reviewed in this report have appeared in data published by the investigators who participated in the regulatory approval process for encainide [1-20].
arrhythmias, and a few with SVT that could not be determined by electrophysiologic studies. The reasons for treatment were relief of symptoms (palpitations, dizziness, syncope, angina, and congestive heart failure) and/or to prevent the occurrence of a more serious event, such as atrial fibrillation with a rapidly conducting accessory pathway, sudden cardiac death, or cardiomyopathy in children with junctional ectopic tachycardia. In electrophysiologic studies, which were conducted in most of the patients, encainide was considered to be effective if SVT was terminated (an uncommon situation) or if the SVT could not be induced after having been induced during the control period. Encainide was considered to be partially effective when the accessory p a t h w a y - - o r in the case of AVNR patients, the AV n o d e - - w a s completely blocked, when the effective refractory period of that pathway was prolonged significantly, or if SVT that had been sustained was no longer sustained when it was induced. Clinically encainide was considered to be effective when the SVT was completely eliminated or occurred only rarely, for instance, a change from almost once a day to twice or less a year. It was considered to be partially effective when the SVT was reduced to a level where both the physician and patient felt that the improvement was sufficient to warrant continuation of treatment. Results P a t i e n t s with A VRT
Patients and Methods
A total of 324 patients were included in the studies covered in the main body of this report, and an additional 48 patients who were studied more recently are covered separately. Patients were those with AV reentry (AVR) of the W P W or Mahaim type (the largest group), but also included AV nodal reentry (AVNR), atrial flutter and/or fibrillation, pediatric junctional ectopic tachycardia, symptomatic premature atrial contractions, automatic supraventricular
The first major trial in the United States was a multicenter, open titration trial with 78 primarily AVRT patients using electrophysiologic studies. All patients had a history of chronic recurrent supraventricular tachycardia. After control electrophysiologic study, encainide was administered IV at a dose of 0.9 mg/kg
Address for correspondenceand reprint requests: Dr. Peter E. Pool, North County Cardiology Research Laboratory, 1087 Devonshire Dr., # 300, Encinitas, CA 92024, USA. 573
574
Pool
over 15 minutes. At the conclusion of initial studies, oral encainide was begun at a dose of 25 mg q6h and increased at 48-hour intervals by 40 to 100 mg/day until anterograde conduction in the accessory pathway was eliminated, as determined by loss of the delta wave on the standard ECG; until an adverse reaction occurred; or until a total dose of 300 mg/day was reached. Patients were evaluated at 3-month intervals for symptoms of recurrent arrhythmias or drug toxicity. The electrophysiologic data showed a clear-cut prolongation of all of the following: the AH and HV intervals (p < .01), the accessory pathway in both the antegrade and retrograde directions (p < .03, p < .04), antegrade AV nodal refractoriness (p < .01), and the shortest cycle length with one-to-one conduction in both directions through the accessory pathway (p < .01). This marked action of encainide on the accessory pathway is one of its important properties. The percentage of WPW patients in whom the accessory pathway was completely blocked was 59% in the antegrade direction and 22% in the retrograde direction. In the electrophysiologic studies, encainide was effective in 49% and partially effective in 38%, so that the response rate was 87%. Clinically, over a mean duration of nearly 2 years, encainide was effective in 67% and partially effective in 19%, for an overall response rate of 86%. As for the predictive nature of the electrophysiologic studies, 94% of the patients in whom encainide was effective or partially effective by electrophysiologic studies also had a long-term favorable clinical response, but a favorable long-term clinical response was also observed in four patients in whom encainide was ineffective by electrophysiologic studies. One can argue whether this is true predictive ability or just an outstanding result relative to electrophysiologic and clinical response. Similar results were obtained in a European trial with 65 predominantly AVRT patients, which was similar in most respects to the U.S. study. Electrophysiologic study was carried out with doses of 0.52.0 mg/kg encainide IV. This was followed with oral dosing beginning at 25 mg tid and advancing up to 500 rag/day, with an average dose of 141 mg/day for an average follow-up of 21.2 months. In this study, the overall electrophysiologic response, including effective and partially effective, was 86%, and in the 2-year clinical phase encainide was effective or partially effective in 76% of the patients. In these two studies and several other similar studies, there were a total of 168 AVRT patients (161 WPW, 5 Mahaim, 1 LGL, and 1 combination), of whom 99 were evaluated with electrophysiologic studies and 142 were followed clinically for an average period of 1.5 years. The overall response rate in the 99
Symptoms
7 6 5 4 o~ c
3
2 o
1
•
0
r-
g sv-r
Allprior Previous hislory 3-month Baseline • . p
Efficacy of Encainide in Supraventricular Arrhythmias P e t e r E. Pool university of California, san DiegoSchool of Medicine; North County CardiologyResearchLaboratory, Encinitas, CA, USA
Summary. This review summarizes the data from all the studies conducted in the United States and Europe that have evaluated the efficacy of encainide in patients with a variety of supraventricular arrhythmias. Using clinical criteria of efficacy, encainide was found to be effective or partially effective in 77% of patients evaluated by electrophysiologic means. Similar levels of efficacy were observed in patients with AV as well as A V nodal reentry arrhythmias. Patients with other forms of supraventricular arrhythmias in smaller series also experienced comparable degrees of efficacy. Encainide was discontinued because of intolerance by 8% of the patients in these studies: 6% because of side effects and 2% because of proarrhythmia.
Key Words. encainide, supraventricular arrhythmias, atrial flutter/fibrillation, A V nodal reentry tachycardia, AV reentry tachycardia, electrophysiology, quinidine
Encainide is a Class IC antiarrhythmic agent that results in a marked slowing of intracardiac conduction with only minimal effects on repolarization. It has been shown to be effective for the therapy of ventricular as well as supraventricular arrhythmias. The following is a review of data (on file at Bristol-Myers) from all the studies that have been conducted in the United States and Europe to evaluate encainide for the control of supraventricular arrhythmias (SVT). Many of the patients reviewed in this report have appeared in data published by the investigators who participated in the regulatory approval process for encainide [1-20].
arrhythmias, and a few with SVT that could not be determined by electrophysiologic studies. The reasons for treatment were relief of symptoms (palpitations, dizziness, syncope, angina, and congestive heart failure) and/or to prevent the occurrence of a more serious event, such as atrial fibrillation with a rapidly conducting accessory pathway, sudden cardiac death, or cardiomyopathy in children with junctional ectopic tachycardia. In electrophysiologic studies, which were conducted in most of the patients, encainide was considered to be effective if SVT was terminated (an uncommon situation) or if the SVT could not be induced after having been induced during the control period. Encainide was considered to be partially effective when the accessory p a t h w a y - - o r in the case of AVNR patients, the AV n o d e - - w a s completely blocked, when the effective refractory period of that pathway was prolonged significantly, or if SVT that had been sustained was no longer sustained when it was induced. Clinically encainide was considered to be effective when the SVT was completely eliminated or occurred only rarely, for instance, a change from almost once a day to twice or less a year. It was considered to be partially effective when the SVT was reduced to a level where both the physician and patient felt that the improvement was sufficient to warrant continuation of treatment. Results P a t i e n t s with A VRT
Patients and Methods
A total of 324 patients were included in the studies covered in the main body of this report, and an additional 48 patients who were studied more recently are covered separately. Patients were those with AV reentry (AVR) of the W P W or Mahaim type (the largest group), but also included AV nodal reentry (AVNR), atrial flutter and/or fibrillation, pediatric junctional ectopic tachycardia, symptomatic premature atrial contractions, automatic supraventricular
The first major trial in the United States was a multicenter, open titration trial with 78 primarily AVRT patients using electrophysiologic studies. All patients had a history of chronic recurrent supraventricular tachycardia. After control electrophysiologic study, encainide was administered IV at a dose of 0.9 mg/kg
Address for correspondenceand reprint requests: Dr. Peter E. Pool, North County Cardiology Research Laboratory, 1087 Devonshire Dr., # 300, Encinitas, CA 92024, USA. 573
574
Pool
over 15 minutes. At the conclusion of initial studies, oral encainide was begun at a dose of 25 mg q6h and increased at 48-hour intervals by 40 to 100 mg/day until anterograde conduction in the accessory pathway was eliminated, as determined by loss of the delta wave on the standard ECG; until an adverse reaction occurred; or until a total dose of 300 mg/day was reached. Patients were evaluated at 3-month intervals for symptoms of recurrent arrhythmias or drug toxicity. The electrophysiologic data showed a clear-cut prolongation of all of the following: the AH and HV intervals (p < .01), the accessory pathway in both the antegrade and retrograde directions (p < .03, p < .04), antegrade AV nodal refractoriness (p < .01), and the shortest cycle length with one-to-one conduction in both directions through the accessory pathway (p < .01). This marked action of encainide on the accessory pathway is one of its important properties. The percentage of WPW patients in whom the accessory pathway was completely blocked was 59% in the antegrade direction and 22% in the retrograde direction. In the electrophysiologic studies, encainide was effective in 49% and partially effective in 38%, so that the response rate was 87%. Clinically, over a mean duration of nearly 2 years, encainide was effective in 67% and partially effective in 19%, for an overall response rate of 86%. As for the predictive nature of the electrophysiologic studies, 94% of the patients in whom encainide was effective or partially effective by electrophysiologic studies also had a long-term favorable clinical response, but a favorable long-term clinical response was also observed in four patients in whom encainide was ineffective by electrophysiologic studies. One can argue whether this is true predictive ability or just an outstanding result relative to electrophysiologic and clinical response. Similar results were obtained in a European trial with 65 predominantly AVRT patients, which was similar in most respects to the U.S. study. Electrophysiologic study was carried out with doses of 0.52.0 mg/kg encainide IV. This was followed with oral dosing beginning at 25 mg tid and advancing up to 500 rag/day, with an average dose of 141 mg/day for an average follow-up of 21.2 months. In this study, the overall electrophysiologic response, including effective and partially effective, was 86%, and in the 2-year clinical phase encainide was effective or partially effective in 76% of the patients. In these two studies and several other similar studies, there were a total of 168 AVRT patients (161 WPW, 5 Mahaim, 1 LGL, and 1 combination), of whom 99 were evaluated with electrophysiologic studies and 142 were followed clinically for an average period of 1.5 years. The overall response rate in the 99
Symptoms
7 6 5 4 o~ c
3
2 o
1
•
0
r-
g sv-r
Allprior Previous hislory 3-month Baseline • . p
