Abstract
Objective: To compare the effect of two sustained-release formulations of metoprolol — metoprolol succinate controlled-release formulation with zero-order kinetics (M CR/Zok) and metoprolol tartrate conventional sustained-release formulation (M ret.) — on total ischaemic burden in patients with stable angina pectoris.
Patients and Methods: This randomised, double-blind, crossover study involved 52 patients with stable angina pectoris and at least six proven ST-segment depressions on 24-hour ambulatory ECG. After a 9-day placebo washout phase, patients were randomised to receive either M CR/Zok 95mg once daily for 4 weeks and then M ret. 200mg once daily for 4 weeks, or the same drugs in the reverse order. ST-segment parameters, cardiological and haemodynamic parameters were evaluated from 24-hour ambulatory ECG recordings.
Results: M CR/Zok and M ret. significantly reduced the median number of ischaemic episodes per 24 hours from 19.15 with placebo to 2.07 with M CR/Zok and 3.74 with M ret. For placebo, M CR/Zok and M ret., the total duration of ischaemia was 39.12, 2.58 and 4.42 minutes, respectively, and the maximum episode duration was 7.5, 1.0 and 1.0 minutes, respectively. The maximum ST-segment depression was 1.65mm with placebo and 1.10mm with M CR/Zok and M ret. The number of angina attacks per 30 days was reduced compared with the placebo phase, from a median of 10.0 to 2.14 with M CR/Zok and 2.68 with M ret. Correspondingly, the number of units of short-acting nitrates consumed fell from 6.67 to 2.14 with M CR/Zok and 2.18 with M ret. M CR/Zok and M ret. lowered the average heart rate from 80.0 to 69.0 and 72.0 beats/min, respectively. All these decreases were significant relative to placebo (p < 0.001), but (with the exception of heart rate) there was no significant difference between M CR/Zok and M ret. for any parameter. 19 patients experienced adverse events with placebo, 24 with M CR/Zok and 30 with M ret.
Conclusion: Our results show that M CR/Zok 95 mg/day or M ret. 200 mg/day taken once daily have similar efficacy on total ischaemic burden in patients with stable angina pectoris. M CR/Zok tends to be better tolerated.
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Bongers, V., Sabin, G.V. Comparison of the Effect of Two Metoprolol Formulations on Total Ischaemic Burden. Clin. Drug Investig. 17, 103–110 (1999). https://doi.org/10.2165/00044011-199917020-00004
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DOI: https://doi.org/10.2165/00044011-199917020-00004