Combination of calcium channel blockers and beta-adrenoceptor blockers forpatients with exercise-induced angina pectoris: a double-blind parallel-group comparison of different classes of calcium channel blockers

Aims The combination of calcium channel blockers and P-adrenoceptor blocker s is more effective for the treatment of exercise-induced angina pectoris t han P-adrenoceptor blocker monotherapy. As ischaemia in exercise-induced an gina is preceded by increase in heart rate, calcium channel blockers with n egative chronotropic properties may perform better for this purpose than no nchronotropic compounds. Methods A 335 patient double-blind parallel-group study comparing 14 day tr eatment with amlodipine 5 and 10 mg, with diltiazem 200 and 300 mg, and mib efradil 50 and 100 mg added to baseline P-adrenoceptor blocker treatment wa s 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 add ition, mibefradil, both low and high dose treatment, produced the longest d elays (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). Th ese effects were linearly correlated with the reduction in rate pressure pr oduct (RPP). Serious symptoms of dizziness occurred significantly more freq uently on mibefradil (P < 0.05), and 19 patients on mibefradil withdrew fro m 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 .