Background: The objective of this study was to compare the efficacy and tolerability of molsidomine prolonged-release 16 mg once-a-day (o.a.d.) with 8 mg twice-a-day (b.i.d.) and placebo in patients with stable angina pectoris.
Methods: After a run-in placebo period of 7 days, the two formulations were compared acutely and then chronically (2 weeks) using cycloergometric tests and a randomized, multicenter, double-blind, double-dummy, crossover design in 533 patients. The quality of life was assessed using the frequency of anginal crises and nitrate sublingual tablets consumption.
Results: Both formulations significantly improved exercise test parameters compared with placebo, being it after acute drug intake or after a 2-week treatment period and independently of spontaneous diurnal variation in exercise tolerance. Noninferiority of molsidomine 16 mg compared with 8 mg was demonstrated with a statistically significant superiority of the 16-mg formulation from 14 to 24 h postintake. Both treatments reduced incidence of anginal attacks and use of sublingual isosorbide dinitrate tablets. Tolerability of active drugs was satisfactory, the incidence of drug-related headache being not significantly different from placebo. Only hypotension was significantly more frequent with molsidomine 16 mg than with placebo, pretrial diastolic blood pressure being significantly lower in these patients than in those who did not develop hypotension during the study.
Conclusions: Both molsidomine formulations were effective in controlling patients' angina, did not induce any habituation and were well tolerated. However, the once-daily 16-mg formulation tended to provide better 24-h protection against myocardial ischemia than the 8-mg b.i.d. formulation.