Mibefradil added to beta-blockers delayed the onset of 1 mm ST-segment depression significantly more than diltiazem or amlodipine (up to 37.0 s difference, P<0.001), but increased dizziness.
RCT (n=335)
Double-blind
Do calcium channel blockers with negative chronotropic properties delay ischaemia more effectively than nonchronotropic calcium channel blockers when added to beta-blockers in patients with exercise-induced angina?
Calcium channel blockers with negative chronotropic properties provide a greater delay of ischaemia in exercise-induced angina when added to beta-blockers, but this benefit is attenuated by a higher risk of intolerable dizziness.
p-value: p=<0.001
AIMS: 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.
Vring et al. (Sat,) conducted a rct in Exercise-induced angina pectoris (n=335). Mibefradil, diltiazem, or amlodipine vs. Baseline beta-blocker treatment (and active comparison between CCBs) was evaluated on Onset of 1 mm ST-segment depression on exercise testing (p=<0.001). Mibefradil added to beta-blockers delayed the onset of 1 mm ST-segment depression significantly more than diltiazem or amlodipine (up to 37.0 s difference, P<0.001), but increased dizziness.
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