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[4 different nitrate preparations with regard to the possible development of tolerance in long-term treatment]
Abstract:
Thirty-two hospitalized patients with angiographically-documented coronary artery disease and stable angina pectoris (NYHA class III) were randomly assigned to one of four treatment groups. After a one-week washout period, baseline examinations (systolic time intervals, blood pressure and exercise ECG) were performed. The patients were then treated with either 20 mg isosorbide dinitrate in sustained-release form (sustained-release ISDN), 20 mg isosorbide 5-mononitrate (IS 5-MN), 2.5 mg buccal nitroglycerin in sustained-release form (NTGB) or 6.5 mg oral nitroglycerin in sustained-release form (NTGO) and one hour thereafter, the heart rate, blood pressure and systolic time intervals were determined. Subsequently, the patients were treated with the respective nitrates four times daily for two weeks. On the seventh and 14th days, the heart rate, blood pressure and systolic time intervals were again determined before and after the first dose of the day. Additionally, after the first dose on the 14th day, an exercise ECG was performed. The effect of the nitrates on the venous capacitance system is reflected by the increase in the PEP/LVET ratio where NTGO and NTGB elicited marked actions and those of sustained-release ISDN and IS 5-MN were of a lesser extent. An effect on systolic and diastolic blood pressure at rest and during exercise could be documented only after administration of NTGB. The anti-ischemic effect of the nitrates was based on the reduction of ST-segment depression during exercise; after two weeks of treatment, sustained-release ISDN and IS 5-MN were associated with complete tolerance development while NTGO continued to exert a slight, and NTGB a clear reduction in ST-segment depression. Personal protocols documented that nitrate consumption and rate of anginal attacks during longterm treatment were unaffected by sustained-release ISDN, IS 5-MN and NTGO, but were reduced by 50% while on treatment with NTGB.