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SEPTEMBER 2001:    Contents

Clin. Cardiol. 24, 608–614 (2001)

Continuous Long-Term Dosing with Oral Slow-Release Isosorbide Dinitrate Does Not Reduce Incidence of Cardiac Events in Patients with Healed Myocardial Infarction

Ken Kanamasa, M.D., Takahiro Hayashi, M.D., Toshihiko Takenaka, M.D., Akio Kimura, M.D., Akiko Ikeda, M.D., Kinji Ishikawa, M.D., on behalf of the secondary prevention group

The First Department of Internal Medicine, Kinki University School of Medicine, Osaka, Japan

Summary

Background: In the short term, isosorbide dinitrate (ISDN) is considered to be therapeutically effective. The long-term effects of treatment with slow-release ISDN are less clear.

Hypothesis: The study was undertaken to investigate the effects of continuous, long-term dosing with oral slow-release ISDN on the incidence of cardiac events in patients with healed myocardial infarction (MI). The study was carried out in accordance with the intention-to-treat principle.

Methods: In all, 1,102 in- and outpatients, of either gender, with healed MI were randomly divided into groups treated with ISDN (n = 470) and not treated with ISDN (n = 632). Patients in the ISDN group received a continuous regimen of 20 mg of oral, long-acting ISDN three times a day, after meals. The mean observation period was 15.0 ± 18.5 months. The primary endpoints were nonfatal and fatal recurrent MI, death from congestive heart failure, and sudden death.

Results: There were no significant differences in the baseline characteristics of the patients in the ISDN and no-treatment groups; nevertheless, significantly more patients in the ISDN group experienced cardiac events. In the ISDN group, 35 patients (7.4%) experienced cardiac events during the observation period, versus only 28 patients (4.4%) in the no-treatment group (p<0.05; odds ratio 1.74; 95% confidence interval 1.04–2.90).

Conclusion: Continuous long-term dosing with oral, slow-release ISDN does not reduce and probably increases the incidence of cardiac events among patients with healed MI.

Key words: isosorbide dinitrate, cardiac events, myocardial infarction, nitrate tolerance

Address for reprints:
Ken Kanamasa, M.D.
The First Department of Internal Medicine
Kinki University School of Medicine
Ohno-Higashi 377-2, Osakasayama
Osaka, 589-8511, Japan
e-mail: kanamasa@med.kindai.ac.jp

Received: August 15, 2000
Accepted with revision: December 26, 2000