Circulation, Vol 82, 1962-1972, Copyright © 1990 by American Heart Association
PH Stone, RS Gibson, SP Glasser, MA DeWood, JD Parker, DT Kawanishi, MH Crawford, FC Messineo, TL Shook and K Raby
Episodes of transient myocardial ischemia during ambulatory activities are
common in patients with stable coronary artery disease and who are often
asymptomatic. Selection of therapy for episodes of asymptomatic ischemia is
limited by a lack of direct comparative studies. To determine the most
effective monotherapy for patients with stable angina and a high frequency
of asymptomatic ischemic episodes, propranolol-LA (mean daily dose, 293
mg), diltiazem-SR (mean daily dose, 350 mg), nifedipine (mean daily dose,
79 mg) were each compared with placebo, each for 2 weeks, in a randomized,
double-blinded, crossover trial. Entry criteria were a positive exercise
treadmill test during placebo therapy characterized by 1.0 mm or more ST
segment depression and angina pectoris, and six or more episodes of
transient ST segment depression of 1.0 mm or more on a 48-hour ambulatory
electrocardiogram. One hundred ninety-four patients were screened, 63 were
eligible and received randomized therapy, of which 56 patients completed at
least two of the four treatment periods and were included in an
intent-to-treat analysis. Fifty patients completed all four treatment
phases and were included in the protocol-completed analysis. Anti-ischemia
efficacy was assessed by 48-hour ambulatory electrocardiographic
monitoring, exercise treadmill tests, and anginal diaries. Ninety-four
percent of all episodes of ambulatory ischemia were asymptomatic. Compared
with placebo, only propranolol was associated with a marked reduction in
all manifestations of asymptomatic ischemia during ambulatory
electrocardiographic monitoring (2.3 versus 1.0 episodes/24 hr; mean
duration of ischemia per 24 hours, 43.6 versus 5.7 minutes; both p less
than 0.0001). Diltiazem's reduction of the frequency of episodes compared
with placebo (2.3 versus 1.9 episodes/24 hr) was associated with a trend (p
= 0.08) in the protocol-completed analysis and with a significant reduction
in the intent-to-treat analysis (p = 0.03). Nifedipine had no significant
effect on any measured variable of ambulatory ischemia. The dosages of
medication used may have been excessive for some patients, and a more
beneficial effect may have been evident at a lower dose. In contrast to the
marked effects of the active agents on ambulatory asymptomatic ischemia,
the effects on exercise performance and angina pectoris were slight. The
active agents modestly improved treadmill exercise duration time until 1 mm
ST segment depression (3%), and only propranolol and diltiazem had
significant effects. Only diltiazem significantly prolonged the total
exercise time. Anginal frequency was significantly decreased by both
propranolol and diltiazem.(ABSTRACT TRUNCATED AT 400 WORDS)
ARTICLES
Comparison of propranolol, diltiazem, and nifedipine in the treatment of ambulatory ischemia in patients with stable angina. Differential effects on ambulatory ischemia, exercise performance, and anginal symptoms. The ASIS Study Group
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
This article has been cited by other articles:
 |
|
 |
|
  F. Enseleit and F. Duru Long-term continuous external electrocardiographic recording: a review. Europace, April 1, 2006; 8(4): 255 - 266. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E Biagini, A F L Schinkel, J J Bax, V Rizzello, R T van Domburg, B J Krenning, M Bountioukos, C Pedone, E C Vourvouri, C Rapezzi, et al. Long term outcome in patients with silent versus symptomatic ischaemia during dobutamine stress echocardiography Heart, June 1, 2005; 91(6): 737 - 742. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. R. Chaitman, S. L. Skettino, J. O. Parker, P. Hanley, J. Meluzin, J. Kuch, C. J. Pepine, W. Wang, J. J. Nelson, D. A. Hebert, et al. Anti-ischemic effects and long-term survival during ranolazine monotherapy in patients with chronic severe angina J. Am. Coll. Cardiol., April 21, 2004; 43(8): 1375 - 1382. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. F. Cohn, K. M. Fox, and C. Daly Silent Myocardial Ischemia Circulation, September 9, 2003; 108(10): 1263 - 1277. [Full Text] [PDF]
|
|
|
|
 |
|
 A Jain, V Wadehra, and A D Timmis Management of stable angina Postgrad. Med. J., June 1, 2003; 79(932): 332 - 336. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Cice, A. Di Benedetto, A. D'Andrea, S. D'Isa, L. Ferrara, P. E. Russo, A. Iacono, and R. Calabro Sustained-Release Diltiazem Reduces Myocardial Ischemic Episodes in End-Stage Renal Disease: A Double-Blind, Randomized, Crossover, Placebo-Controlled Trial J. Am. Soc. Nephrol., April 1, 2003; 14(4): 1006 - 1011. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Pelter, M. G. Adams, and B. J. Drew Association of Transient Myocardial Ischemia With Adverse In-Hospital Outcomes for Angina Patients Treated in a Telemetry Unit or a Coronary Care Unit Am. J. Crit. Care., July 1, 2002; 11(4): 318 - 325. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Maxwell, M. P. Zapien, G. L. Pearce, G. MacCallum, and P. H. Stone Randomized trial of a medical food for the dietary management of chronic, stable angina J. Am. Coll. Cardiol., January 2, 2002; 39(1): 37 - 45. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. E Newby and K. A A Fox Unstable angina: the first 48 hours and later in-hospital management Br. Med. Bull., October 1, 2001; 59(1): 69 - 87. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Picano and on behalf of the PISA study group Dipyridamole in chronic stable angina pectoris. A randomized, double blind, placebo-controlled, parallel group study Eur. Heart J., October 1, 2001; 22(19): 1785 - 1793. [Abstract] [PDF]
|
|
|
|
 |
|
 D. R. Abernethy and J. B. Schwartz Calcium-Antagonist Drugs N. Engl. J. Med., November 4, 1999; 341(19): 1447 - 1457. [Full Text] [PDF]
|
|
|
|
|
|
M. H. Crawford, S. J. Bernstein, P. C. Deedwania, J. P. DiMarco, K. J. Ferrick, A. Garson Jr, L. A. Green, H. L. Greene, M. J. Silka, P. H. Stone, et al. ACC/AHA guidelines for ambulatory electrocardiography: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the Guidelines for Ambulatory Electrocardiography) developed in collaboration with the North American Society for Pacing and Electrophysiology J. Am. Coll. Cardiol., September 1, 1999; 34(3): 912 - 948. [Full Text] [PDF]
|
|
|
|
|
|
R. R. Arora, T. M. Chou, D. Jain, B. Fleishman, L. Crawford, T. McKiernan, and R. W. Nesto The multicenter study of enhanced external counterpulsation (MUST-EECP): effect of EECP on exercise-induced myocardial ischemia and anginal episodes J. Am. Coll. Cardiol., June 1, 1999; 33(7): 1833 - 1840. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D de Bono Investigation and management of stable angina: revised guidelines 1998 Heart, May 1, 1999; 81(5): 546 - 555. [Full Text]
|
|
|
|
 |
|
 W. B. Stason, C. H. Schmid, D. Niedzwiecki, G. W. Whiting, J.-F. Caubet, D. Cory, D. Luo, S. D. Ross, and T. C. Chalmers Safety of Nifedipine in Angina Pectoris : A Meta-Analysis Hypertension, January 1, 1999; 33(1): 24 - 31. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Tzivoni, H. Kadr, S. Braat, W. Rutsch, J. A. Ramires, and I. Kobrin Efficacy of Mibefradil Compared With Amlodipine in Suppressing Exercise-Induced and Daily Silent Ischemia : Results of a Multicenter, Placebo-Controlled Trial Circulation, October 21, 1997; 96(8): 2557 - 2564. [Abstract] [Full Text]
|
|
|
|
|
|
M. Chiariello and C. Indolfi Silent Myocardial Ischemia in Patients With Diabetes Mellitus Circulation, June 15, 1996; 93(12): 2089 - 2091. [Full Text]
|
|
|
|
 |
|
 North of England Stable Angina Guideline Developme North of England evidence based guidelines development project: summary version of evidence based guideline for the primary care management of stable angina BMJ, March 30, 1996; 312(7034): 827 - 832. [Full Text]
|
|