Continuous long-term dosing with oral slow-release isosorbide dinitrate does not reduce incidence of cardiac events in patients with healed myocardial infarction.
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.


OBJECTIVE
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).


CONCLUSIONS
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.
Kanamasa
K
K
The First Department of Internal Medicine, Kinki University School of Medicine, Osaka, Japan. kanamasa@med.kindai.ac.jp
Hayashi
T
T
Takenaka
T
T
Kimura
A
A
Ikeda
A
A
Ishikawa
K
K
D000284:Administration, Oral; D000328:Adult; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006331:Heart Diseases / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D015994:Incidence; D007548:Isosorbide Dinitrate / Q000008:administration & dosage* / Q000627:therapeutic use*; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000401:mortality; D016019:Survival Analysis; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000627:therapeutic use*
D003692:Delayed-Action Preparations; D014665:Vasodilator Agents; D007548:Isosorbide Dinitrate