Effect of metoprolol and amlodipine on myocardial total ischaemic burden in patients with stable angina pectoris

Abstract

A randomized double-blind cross-over study to assess the effect on myocardial total ischaemic burden and the anti-anginal efficacy of the beta-1-blocker metoprolol given as metoprolol CR/Zok versus the calcium channel blocker amlodipine, both given in the recommended and commonly used doses of 100 mg o.d. and 5 mg o.d., respectively. Fifty-two patients with a history of stable exercise-induced angina pectoris and at least six episodes of significant ST-segment depression during 24-h ambulatory electrocardiographic monitoring after 9 days of placebo were included in the study. The patients first completed a 9-day placebo run-in phase with additional administration of a long-acting nitrate during the first 7 days. They then received in a randomized sequence metoprolol CR/Zok and amlodipine each for 4 weeks. During placebo treatment and at the end of each phase of active treatment the patients' clinical progress was assessed and a 24-h ECG monitor performed. Forty-seven patients completed the two 4-week treatment periods. Five patients withdrew from the study. The number of ischaemic episodes during 24 h was 30.4 at baseline with placebo, which was reduced significantly by both treatments (P<0.005) to 6.8 episodes after metoprolol and 15.8 episodes after amlodipine treatment (P<0.001 for the difference between the treatment groups). Metoprolol and amlodipine reduced the total duration of ischaemic episodes from 86.0 min to 15-1 and 48.3 min with a mean episode duration of 1.1 and 2.6 min, respectively. Twenty patients on metoprolol (42.6%) and four on amlodipine (8.4%) showed no ST-segment depression at the end of treatment. Baseline heart rate of 80 b.p.m. decreased by 11.1 b.p.m. after metoprolol and increased by 4b.p.m. after amlodipine. Anginal attacks were reduced from 14.8 attacks per week at baseline to 2.4 attacks on metoprolol and 4.4 attacks on amlodipine treatment. For all variables the observed changes from baseline were significant after either treatment (P<0.005) with a significantly more pronounced effect in favour of metoprolol (P<0.0001). Ten patients reported nine different adverse events during metoprolol treatment. On amlodipine, 12 patients were affected by 11 different symptoms leading to three treatment withdrawals. On metoprolol one patient withdrew due to adverse events. Both drugs reduce total ischaemic burden by reducing ischaemic episodes and antianginal attacks, with a significantly greater effect from metoprolol 100 mg o.d. as compared to amlodipine 5 mg o.d.