Comparison of the effect of two metoprolol formulations on total ischaemicburden

Objective: To compare the effect of two sustained-release formulations of m etoprolol - metoprolol succinate controlled-release formulation with zero-o rder kinetics (M CR/Zok) and metoprolol tartrate conventional sustained-rel ease formulation (M ret.) - on total ischaemic burden in patients with stab le angina pectoris. Patients and Methods: This randomised, double-blind, crossover study involv ed 52 patients with stable angina pectoris and at least six proven ST-segme nt depressions on 24-hour ambulatory EGG. After a 9-day placebo washout pha se, patients were randomised to receive either M CR/Zok 95 mg once daily fo r 4 weeks and then M ret. 200mg once daily for 4 weeks, or the same drugs i n 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 isc haemic 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 o f 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 S T-segment depression was 1.65 mm with placebo and 1.10 mm 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 wit h M ret. Correspondingly, the number of units of short-acting nitrates cons umed 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 exper ienced 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 t aken once daily have similar efficacy on total ischaemic burden in patients with stable angina pectoris. M CR/Zok tends to be better tolerated.