Abrupt withdrawal of isosorbide-5-mononitrate in Durules (Imdur) after long term treatment in patients with stable angina pectoris

Abstract

In a single-blind study of 6 weeks' duration, 32 patients with stable angina pectoris, who had been receiving controlled-release, Durules, isosorbide-5-mononitrate (Imdur) 60 to 180 mg daily for at least 1 year, were assessed after abrupt withdrawal of the nitrate. After 2 weeks of placebo treatment nitrate therapy was re-instituted, and the patients followed for another 2 weeks. The possibility of development of tolerance and rebound phenomena was also investigated. Three patients experienced severe anginal symptoms necessitating hospitalization when controlled-release isosorbide-5-mononitrate was withdrawn abruptly. Patients complained of more severe anginal symptoms during the placebo period, experienced more frequent anginal attacks and used more glyceryl trinitrate tablets than during active treatment. ST segment changes during exercise were more pronounced with placebo. After controlled-release isosorbide-5-mononitrate was re-introduced, these variables indicated significant improvement. On the other hand, no deterioration occurred in exercise performance during the placebo phase. Responsiveness to glyceryl trinitrate was maintained, as shown by comparisons of exercise tests performed after the long term treatment and during the placebo phase. Controlled-release isosorbide-5-mononitrate retains a beneficial effect in patients with angina pectoris during prolonged use, although some attenuation of the effect is seen. Abrupt withdrawal of the drug is not recommended because of the possibility of severe exacerbation of anginal symptoms, although no clearcut rebound phenomena were seen.