Effect of amlodipine, atenolol and their combination on myocardial ischemia during treadmill exercise and ambulatory monitoring. Canadian Amlodipine/Atenolol in Silent Ischemia Study (CASIS) Investigators.
OBJECTIVE
This study compared the effects of amlodipine, atenolol and their combination on ischemia during treadmill testing and 48-h ambulatory monitoring.


BACKGROUND
It is not known whether anti-ischemic drugs exert similar effects on ischemia during ambulatory monitoring and exercise treadmill testing.


METHODS
Patients with stable coronary artery disease and ischemia during treadmill testing and ambulatory monitoring were randomized to receive amlodipine (n = 51) or atenolol (n = 49). Each group underwent a counterbalanced, crossover evaluation of single drug and placebo, followed by evaluation of the combination.


RESULTS
Amlodipine and the combination prolonged exercise time to 0.1-mV ST segment depression by 29% and 34%, respectively (p < 0.001) versus 3% for atenolol (p = NS). During ambulatory monitoring, the frequency of ischemic episodes decreased by 28% with amlodipine (p = 0.083 [NS]), by 57% with atenolol (p < 0.001) and by 72% with the combination (p < 0.05 vs. both single drugs; p < 0.001 vs. placebo). Suppression of ischemia during exercise testing and ambulatory monitoring was similar in patients with and without exercise-induced angina. Exercise time to angina improved by 29% with amlodipine (p < 0.01), by 16% with atenolol (p < 0.05) and by 39% with the combination (p < 0.005 vs. placebo, atenolol and amlodipine). In patients with angina, total exercise time improved by 16% with amlodipine (p < 0.001), by 4% with atenolol (p = NS) and by 19% with the combination (p < 0.05 vs. placebo and either single drug). In those patients without angina, no therapy significantly improved total exercise time.


CONCLUSIONS
Ischemia during treadmill testing was more effectively suppressed by amlodipine, whereas ischemia during ambulatory monitoring was more effectively suppressed by atenolol. The combination was more effective than either single drug in both settings.
Davies
R F
RF
University of Ottawa Heart Institute, Ontario, Canada.
Habibi
H
H
Klinke
W P
WP
Dessain
P
P
Nadeau
C
C
Phaneuf
D C
DC
Lepage
S
S
Raman
S
S
Herbert
M
M
Foris
K
K
D017311:Amlodipine / Q000494:pharmacology / Q000627:therapeutic use*; D001262:Atenolol / Q000494:pharmacology / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004359:Drug Therapy, Combination; D015716:Electrocardiography, Ambulatory; D005080:Exercise Test; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D013997:Time Factors
D017311:Amlodipine; D001262:Atenolol