Combination of calcium channel blockers and beta-adrenoceptor blockers for patients with exercise-induced angina pectoris: a double-blind parallel-group comparison of different classes of calcium channel blockers. Netherlands Working Group on Cardiovascular Research (WCN).
OBJECTIVE
The combination of calcium channel blockers and beta-adrenoceptor blockers is more effective for the treatment of exercise-induced angina pectoris than beta-adrenoceptor blocker monotherapy. As ischaemia in exercise-induced angina is preceded by increase in heart rate, calcium channel blockers with negative chronotropic properties may perform better for this purpose than nonchronotropic compounds.


METHODS
A 335 patient double-blind parallel-group study comparing 14 day treatment with amlodipine 5 and 10 mg, with diltiazem 200 and 300 mg, and mibefradil 50 and 100 mg added to baseline beta-adrenoceptor blocker treatment was performed. Exercise testing (ETT) was performed by bicycle ergometry.


RESULTS
Although none of the calcium channel blockers improved duration of exercise or amount of workload, all significantly delayed onset of 1 mm ST-segment depression on ETT (P<0.001 for any treatment vs baseline). In addition, mibefradil, both low and high dose treatment, produced the longest delays (low dose: different from diltiazem and amlodipine by 24.1 and 29.8 s, respectively, P<0. 003 and <0.001; high dose: different from diltiazem and amlodipine by 33.7 and 37.0 s, respectively, P<0.001 and <0.001). These effects were linearly correlated with the reduction in rate pressure product (RPP). Serious symptoms of dizziness occurred significantly more frequently on mibefradil (P<0.05), and 19 patients on mibefradil withdrew from trial.


CONCLUSIONS
Calcium channel blockers with negative chronotropic properties provide greater delay of ischaemia in patients with exercise-induced angina, but the concomitant risk of intolerable dizziness attenuates this benefit.
Van Der Vring
J A
JA
Merwede Hospital, Dodrecht, Sleidrecht, The Netherlands.
Daniëls
M C
MC
Holwerda
N J
NJ
Withagen
P J
PJ
Schelling
A
A
Cleophas
T J
TJ
Hendriks
M G
MG
D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D017311:Amlodipine / Q000009:adverse effects / Q000627:therapeutic use; D000787:Angina Pectoris / Q000188:drug therapy* / Q000503:physiopathology; D001562:Benzimidazoles / Q000009:adverse effects / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000627:therapeutic use*; D004110:Diltiazem / Q000009:adverse effects / Q000627:therapeutic use; D004244:Dizziness / Q000139:chemically induced; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D015444:Exercise / Q000502:physiology*; D005080:Exercise Test / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D020748:Mibefradil; D008875:Middle Aged; D018570:Risk Assessment; D013764:Tetrahydronaphthalenes / Q000009:adverse effects / Q000627:therapeutic use
D000319:Adrenergic beta-Antagonists; D001562:Benzimidazoles; D002121:Calcium Channel Blockers; D013764:Tetrahydronaphthalenes; D017311:Amlodipine; D020748:Mibefradil; D004110:Diltiazem