EFFECT OF METOPROLOL AND AMLODIPINE ON MYOCARDIAL TOTAL ISCHEMIC BURDEN IN PATIENTS WITH STABLE ANGINA-PECTORIS

Objective: A randomized double-blind cross-over study to assess the ef fect on myocardial total ischaemic burden and the anti-anginal efficac y of the beta-1-blocker metoprolol given as metoprolol CR/Zok versus t he calcium channel blocker amlodipine, both given in the recommended a nd commonly used doses of 100 mg o.d. and 5 mg o.d., respectively. Met hod: Fifty-two patients with a history of stable exercise-induced angi na pectoris and at least six episodes of significant ST-segment depres sion during 24-h ambulatory electrocardiographic monitoring after 9 da ys 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 rando mized sequence metoprolol CR/Zok and amlodipine each for 4 weeks. Duri ng placebo treatment and at the end of each phase of active treatment the patients' clinical progress was assessed and a 24-h ECG monitor pe rformed. Results: Forty-seven patients completed the two 4-week treatm ent periods. Five patients withdrew from the study. The number of isch aemic episodes during 24 h was 30.4 at baseline with placebo, which wa s reduced significantly by both treatments (P<0.005) to 6.8 episodes a fter metoprolol and 15.8 episodes after amlodipine treatment (P<0.001 for the difference between the treatment groups). Metoprolol and amlod ipine reduced the total duration of ischaemic episodes from 86.0 min t o 15.1 and 48.3 min with a mean episode duration of 1.1 and 2.6 min, r espectively. Twenty patients on metoprolol (42.6%) and four on amlodip ine (8.4%) showed no ST-segment depression at the end of treatment. Ba seline heart rate of 80 b.p.m. decreased by II lb.p.m. after metoprolo l and increased by 4 b.p.m. after amlodipine. Anginal attacks were red uced from 14.8 attacks per week at baseline to 2.4 attacks on metoprol ol and 4 4 attacks on amlodipine treatment. For all variables the obse rved changes from baseline were significant after either treatment (P< 0.005) with a significantly more pronounced effect in favour of metopr olol (P<0.0001). Ten patients reported nine different adverse events d uring metoprolol treatment. On amlodipine, 12 patients were affected b y II different symptoms leading to three treatment withdrawals. On met oprolol one patient withdrew due to adverse events. Conclusion: Both d rugs reduce total ischaemic burden by reducing ischaemic episodes and antianginal attacks, with a significantly greater effect from metoprol ol 100 mg o.d. as compared to amlodipine 5 mg o.d.