Combination of calcium channel blockers and beta-blockers for patients with exercise-induced angina pectoris: Beneficial effect of calcium channel blockers largely determined by their effect on heart rate

The combination of calcium channel blockers and beta-blockers is more effec tive for the treatment of exercise-induced angina pectoris than beta-blocke r monotherapy. As ischemia in exercise-induced angina is essentially preced ed by an increase in heart rate, calcium channel blockers with a negative c hronotropic property may perform better for this purpose than nonchronotrop ic compounds. A 335-patient, 10-week, double-blind, parallel-group comparis on of amlodipine 5 mg and 10 mg, diltiazem 200 mg and 300 mg, and mibefradi l 50 mg and 100 mg treatment added to baseline beta-blocker treatment was p erformed. Exercise testing (ETT) was performed by bicycle ergometry. All of the calcium channels blockers significantly delayed the onset of 1 mm ST-s egment depression on ETT(p < 0.001 for any treatment vs. baseline). In addi tion, mibefradil, in bath low- and high-dose treatments, produced the large st delays (low dose: different from diltiazem and amlodipine by 24.1 and 29 .8 seconds, respectively: p < 0.003 and < 0.001; high dose: different from diltiazem and amlodipine by 33.7 and 37.0 seconds, respectively p < 0.001 a nd < 0.001). A stepwise logistic regression analysis revealed that this ben eficial effect of calcium channel blockers was largely dependent an their e ffect on heart rate. Serious symptoms of dizziness likewise occurred signif icantly more frequently on mibefradil (p < 0.05 vs. diltiazem) and urged no fewer than 19 patients on mibefradil to withdraw from the trial. The autho rs conclude that calcium channel blockers with a negative chronotropic prop erty provide a better delay of ischemia in patients with exercise-induced a ngina, but the concomitant risk of intolerable dizziness may reduce this be nefit. (C) 1999 the American College of Clinical Pharmacology.