Combination of calcium channel blockers and β‐adrenoceptor blockers for patients with exercise‐induced angina pectoris: a double‐blind parallel‐group comparison of different classes of calcium channel blockers

Abstract

Aims The combination of calcium channel blockers and b-adrenoceptor blockers is more effective for the treatment of exercise-induced angina pectoris than b-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 b-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.

Resting Heart Rate in Cardiovascular Disease

“…4). Regression analysis showed that the beneficial anti-ischemic effect of the drugs was largely dependent on their effect on HR (22). Mortality in patients with heart failure.…”

The Role of Ivabradine in the Management of Angina Pectoris

“…Previous attempts to optimise heart rate control by adding non-dihydropyridine calcium antagonists on top of background beta blocker therapy have been unsuccessful due to the development of limiting side-effects [ 43 ] and should therefore be avoided. More recently, in the ASSOCIATE trial, ivabradine (5 to 7.5 mg BD) as add-on therapy in patients already established on beta blockers was effective in significantly improving exercise duration and time to both electrocardiographic evidence of ischaemia and symptomatic angina on treadmill exercise testing (Fig.…”

A Double-Blind, Parallel-Group Study of Amlodipine versus Long-Acting Nitrate in the Management of Elderly Patients with Stable Angina

“…The combination use of calcium channel blockers and β-blockers in the treatment of angina has been investigated [17, 20, 21, 22]. In a study undertaken to compare the effects of amlodipine, atenolol and the combination in patients with stable angina pectoris, the two individual agents alone were as effective as their combination in terms of time to onset of S–T depression >1 mm, time to onset of angina, total exercise time and maximum achieved workload [17].…”