Combination propranolol and bepridil therapy in stable angina pectoris

William H. Frishman, Shlomo Charlap, D. John Farnham, Henry S. Sawin, Eric L. Michelson, Michael H. Crawford, Robert DiBianco, John B. Kostis, Stephen R. Zellner, David D. Michie, Richard J. Katz, Syed M. Mohiuddin, Udho Thadani

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

The safety and efficacy of bepridil plus propranolol therapy were investigated in a placebo-controlled, parallel-design, double-blind trial in 56 patients who were not responding to propranolol alone. Patients entering the study were receiving an average propranolol dosage of 131 mg/day (range 20 to 240). For the first 2 weeks of the study they were given placebo in addition to their propranolol dose, and then were randomized to receive continued placebo plus propranolol or bepridil plus propranolol therapy. The bepridil dosage was adjusted over the 8 weeks of active treatment to an average of 273 mg/day (range 200 to 400). The double-blind treatment period was followed by a 3-week washout period during which all patients received propranolol and placebo. The effects of treatment on the frequency of angina attacks, nitroglycerin consumption, exercise performance (treadmill-modified Bruce protocol) and Holter electrocardiogram (ECG) were assessed. Propranolol and bepridil plasma levels also were obtained. Improved antianginal efficacy and reduced nitroglycerin consumption were noted when bepridil was added to propranolol (p <0.01). During 8 weeks of combination treatment, exercise tolerance increased 1.0 ± 1.2 minutes from a baseline of 7.3 ± 2.2 with bepridil plus propranolol compared with an increase of 0.02 ± 1.3 minutes from a baseline of 7.6 ± 2.9 with placebo plus propranolol (p <0.01). With bepridil plus propranolol, there were also increases in exercise time to onset of angina (p <0.04), exercise time to 1-mm electrocardiographic ST-segment depression (p <0.06) and total work (p <0.03) compared with placebo plus propranolol therapy. Resting heart rate was reduced a maximum of 2 beats/min with combination treatment compared with propranolol alone, and no differences in blood pressure between treatment groups were observed. There were no clinically significant rhythm changes on Holter ECG with combination treatment, and bepridil treatment had no effect on plasma propranolol levels. Bepridil did prolong the QTc interval on resting ECG by a mean of 37 ± 39 millisecond. Adverse effects were mild with bepridil plus propranolol and greater in frequency than those with placebo plus propranolol. With cessation of bepridil, patients returned toward the angina frequency and exercise tolerance levels seen at baseline with propranolol alone. The addition of bepridil to propranolol provided safe and effective antianginal therapy in patients whose angina was not controlled by propranolol alone.

Original languageEnglish
JournalAmerican Journal of Cardiology
Volume55
Issue number7
DOIs
StatePublished - Mar 15 1985

Fingerprint

Bepridil
Stable Angina
Propranolol
Therapeutics
Placebos
Electrocardiography
Exercise Tolerance
Nitroglycerin
Exercise

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Frishman, W. H., Charlap, S., Farnham, D. J., Sawin, H. S., Michelson, E. L., Crawford, M. H., ... Thadani, U. (1985). Combination propranolol and bepridil therapy in stable angina pectoris. American Journal of Cardiology, 55(7). https://doi.org/10.1016/0002-9149(85)90805-7

Combination propranolol and bepridil therapy in stable angina pectoris. / Frishman, William H.; Charlap, Shlomo; Farnham, D. John; Sawin, Henry S.; Michelson, Eric L.; Crawford, Michael H.; DiBianco, Robert; Kostis, John B.; Zellner, Stephen R.; Michie, David D.; Katz, Richard J.; Mohiuddin, Syed M.; Thadani, Udho.

In: American Journal of Cardiology, Vol. 55, No. 7, 15.03.1985.

Research output: Contribution to journalArticle

Frishman, WH, Charlap, S, Farnham, DJ, Sawin, HS, Michelson, EL, Crawford, MH, DiBianco, R, Kostis, JB, Zellner, SR, Michie, DD, Katz, RJ, Mohiuddin, SM & Thadani, U 1985, 'Combination propranolol and bepridil therapy in stable angina pectoris', American Journal of Cardiology, vol. 55, no. 7. https://doi.org/10.1016/0002-9149(85)90805-7
Frishman WH, Charlap S, Farnham DJ, Sawin HS, Michelson EL, Crawford MH et al. Combination propranolol and bepridil therapy in stable angina pectoris. American Journal of Cardiology. 1985 Mar 15;55(7). https://doi.org/10.1016/0002-9149(85)90805-7
Frishman, William H. ; Charlap, Shlomo ; Farnham, D. John ; Sawin, Henry S. ; Michelson, Eric L. ; Crawford, Michael H. ; DiBianco, Robert ; Kostis, John B. ; Zellner, Stephen R. ; Michie, David D. ; Katz, Richard J. ; Mohiuddin, Syed M. ; Thadani, Udho. / Combination propranolol and bepridil therapy in stable angina pectoris. In: American Journal of Cardiology. 1985 ; Vol. 55, No. 7.
@article{b923029f3a3b4b8c9874a2b6bdf44e88,
title = "Combination propranolol and bepridil therapy in stable angina pectoris",
abstract = "The safety and efficacy of bepridil plus propranolol therapy were investigated in a placebo-controlled, parallel-design, double-blind trial in 56 patients who were not responding to propranolol alone. Patients entering the study were receiving an average propranolol dosage of 131 mg/day (range 20 to 240). For the first 2 weeks of the study they were given placebo in addition to their propranolol dose, and then were randomized to receive continued placebo plus propranolol or bepridil plus propranolol therapy. The bepridil dosage was adjusted over the 8 weeks of active treatment to an average of 273 mg/day (range 200 to 400). The double-blind treatment period was followed by a 3-week washout period during which all patients received propranolol and placebo. The effects of treatment on the frequency of angina attacks, nitroglycerin consumption, exercise performance (treadmill-modified Bruce protocol) and Holter electrocardiogram (ECG) were assessed. Propranolol and bepridil plasma levels also were obtained. Improved antianginal efficacy and reduced nitroglycerin consumption were noted when bepridil was added to propranolol (p <0.01). During 8 weeks of combination treatment, exercise tolerance increased 1.0 ± 1.2 minutes from a baseline of 7.3 ± 2.2 with bepridil plus propranolol compared with an increase of 0.02 ± 1.3 minutes from a baseline of 7.6 ± 2.9 with placebo plus propranolol (p <0.01). With bepridil plus propranolol, there were also increases in exercise time to onset of angina (p <0.04), exercise time to 1-mm electrocardiographic ST-segment depression (p <0.06) and total work (p <0.03) compared with placebo plus propranolol therapy. Resting heart rate was reduced a maximum of 2 beats/min with combination treatment compared with propranolol alone, and no differences in blood pressure between treatment groups were observed. There were no clinically significant rhythm changes on Holter ECG with combination treatment, and bepridil treatment had no effect on plasma propranolol levels. Bepridil did prolong the QTc interval on resting ECG by a mean of 37 ± 39 millisecond. Adverse effects were mild with bepridil plus propranolol and greater in frequency than those with placebo plus propranolol. With cessation of bepridil, patients returned toward the angina frequency and exercise tolerance levels seen at baseline with propranolol alone. The addition of bepridil to propranolol provided safe and effective antianginal therapy in patients whose angina was not controlled by propranolol alone.",
author = "Frishman, {William H.} and Shlomo Charlap and Farnham, {D. John} and Sawin, {Henry S.} and Michelson, {Eric L.} and Crawford, {Michael H.} and Robert DiBianco and Kostis, {John B.} and Zellner, {Stephen R.} and Michie, {David D.} and Katz, {Richard J.} and Mohiuddin, {Syed M.} and Udho Thadani",
year = "1985",
month = "3",
day = "15",
doi = "10.1016/0002-9149(85)90805-7",
language = "English",
volume = "55",
journal = "American Journal of Cardiology",
issn = "0002-9149",
publisher = "Elsevier Inc.",
number = "7",

}

TY - JOUR

T1 - Combination propranolol and bepridil therapy in stable angina pectoris

AU - Frishman, William H.

AU - Charlap, Shlomo

AU - Farnham, D. John

AU - Sawin, Henry S.

AU - Michelson, Eric L.

AU - Crawford, Michael H.

AU - DiBianco, Robert

AU - Kostis, John B.

AU - Zellner, Stephen R.

AU - Michie, David D.

AU - Katz, Richard J.

AU - Mohiuddin, Syed M.

AU - Thadani, Udho

PY - 1985/3/15

Y1 - 1985/3/15

N2 - The safety and efficacy of bepridil plus propranolol therapy were investigated in a placebo-controlled, parallel-design, double-blind trial in 56 patients who were not responding to propranolol alone. Patients entering the study were receiving an average propranolol dosage of 131 mg/day (range 20 to 240). For the first 2 weeks of the study they were given placebo in addition to their propranolol dose, and then were randomized to receive continued placebo plus propranolol or bepridil plus propranolol therapy. The bepridil dosage was adjusted over the 8 weeks of active treatment to an average of 273 mg/day (range 200 to 400). The double-blind treatment period was followed by a 3-week washout period during which all patients received propranolol and placebo. The effects of treatment on the frequency of angina attacks, nitroglycerin consumption, exercise performance (treadmill-modified Bruce protocol) and Holter electrocardiogram (ECG) were assessed. Propranolol and bepridil plasma levels also were obtained. Improved antianginal efficacy and reduced nitroglycerin consumption were noted when bepridil was added to propranolol (p <0.01). During 8 weeks of combination treatment, exercise tolerance increased 1.0 ± 1.2 minutes from a baseline of 7.3 ± 2.2 with bepridil plus propranolol compared with an increase of 0.02 ± 1.3 minutes from a baseline of 7.6 ± 2.9 with placebo plus propranolol (p <0.01). With bepridil plus propranolol, there were also increases in exercise time to onset of angina (p <0.04), exercise time to 1-mm electrocardiographic ST-segment depression (p <0.06) and total work (p <0.03) compared with placebo plus propranolol therapy. Resting heart rate was reduced a maximum of 2 beats/min with combination treatment compared with propranolol alone, and no differences in blood pressure between treatment groups were observed. There were no clinically significant rhythm changes on Holter ECG with combination treatment, and bepridil treatment had no effect on plasma propranolol levels. Bepridil did prolong the QTc interval on resting ECG by a mean of 37 ± 39 millisecond. Adverse effects were mild with bepridil plus propranolol and greater in frequency than those with placebo plus propranolol. With cessation of bepridil, patients returned toward the angina frequency and exercise tolerance levels seen at baseline with propranolol alone. The addition of bepridil to propranolol provided safe and effective antianginal therapy in patients whose angina was not controlled by propranolol alone.

AB - The safety and efficacy of bepridil plus propranolol therapy were investigated in a placebo-controlled, parallel-design, double-blind trial in 56 patients who were not responding to propranolol alone. Patients entering the study were receiving an average propranolol dosage of 131 mg/day (range 20 to 240). For the first 2 weeks of the study they were given placebo in addition to their propranolol dose, and then were randomized to receive continued placebo plus propranolol or bepridil plus propranolol therapy. The bepridil dosage was adjusted over the 8 weeks of active treatment to an average of 273 mg/day (range 200 to 400). The double-blind treatment period was followed by a 3-week washout period during which all patients received propranolol and placebo. The effects of treatment on the frequency of angina attacks, nitroglycerin consumption, exercise performance (treadmill-modified Bruce protocol) and Holter electrocardiogram (ECG) were assessed. Propranolol and bepridil plasma levels also were obtained. Improved antianginal efficacy and reduced nitroglycerin consumption were noted when bepridil was added to propranolol (p <0.01). During 8 weeks of combination treatment, exercise tolerance increased 1.0 ± 1.2 minutes from a baseline of 7.3 ± 2.2 with bepridil plus propranolol compared with an increase of 0.02 ± 1.3 minutes from a baseline of 7.6 ± 2.9 with placebo plus propranolol (p <0.01). With bepridil plus propranolol, there were also increases in exercise time to onset of angina (p <0.04), exercise time to 1-mm electrocardiographic ST-segment depression (p <0.06) and total work (p <0.03) compared with placebo plus propranolol therapy. Resting heart rate was reduced a maximum of 2 beats/min with combination treatment compared with propranolol alone, and no differences in blood pressure between treatment groups were observed. There were no clinically significant rhythm changes on Holter ECG with combination treatment, and bepridil treatment had no effect on plasma propranolol levels. Bepridil did prolong the QTc interval on resting ECG by a mean of 37 ± 39 millisecond. Adverse effects were mild with bepridil plus propranolol and greater in frequency than those with placebo plus propranolol. With cessation of bepridil, patients returned toward the angina frequency and exercise tolerance levels seen at baseline with propranolol alone. The addition of bepridil to propranolol provided safe and effective antianginal therapy in patients whose angina was not controlled by propranolol alone.

UR - http://www.scopus.com/inward/record.url?scp=0021960213&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0021960213&partnerID=8YFLogxK

U2 - 10.1016/0002-9149(85)90805-7

DO - 10.1016/0002-9149(85)90805-7

M3 - Article

VL - 55

JO - American Journal of Cardiology

JF - American Journal of Cardiology

SN - 0002-9149

IS - 7

ER -