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European Heart Journal 1988 9(12):1339-1347;
Copyright © 1988 by the European Society of Cardiology.
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© 1988 The European Society of Cardiology

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

N. REHNQVIST1, G. OLSSON1, J. ENGVALL2, U. ROSENQVIST2, G. NYBERG3, A. ÅBERG3, G. ULVENSTAM3, A. UUSITALO4, O. KEYRILÄINEN4, P. REINIKAINEN4, R. HÄRKÖNEN5 and B. NILSSON6

1Danderyd Hospital Sweden
2Oskarshamn Hospital Sweden
3Östra Hospital GÖteborg, Sweden
4Tampere University Central Hospital Finland
5North Karelia Central Hospital Joensuu, Finland
6AB Hässle Sweden

Received 22 January 1988; revised 28 June 1988; .

Abstract

In a single-blind study of 6 weeks' duration, 32 patients with stable angina pectoris, who hadbeen receiving controlled-release, Durules®, isosorbide-5-monoitrate (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 antoher 2 weeks. The possibility of developemnt of tolerance and rebound phenomena was also investigated.

Three patietns experienced severe anginal symptoms necessitating hospitalization when controlled-release isosorbide-5-monoitrate was withdrawn abruptly.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 comoparisons 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 withdrawarl of the drug is not recommended because of the possibility of severe exacerbation of anginal symptoms, although no clearcut rebound phenomena were seen.

Key Words: Controlled-release isosorbide-5-monoitrate, • Angina pectoris, • abrupt withdrawal, • tolerance.


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