Intermittent nitrate therapy for prior myocardial infaraction does not induce rebound angina nor reduce cardiac events.
OBJECTIVE
Long-term nitrate therapy for ischemic heart disease may cause drug tolerance which diminishes its beneficial effects; consequently, intermittent administration of nitrates is recommended. With this regimen, however, the potential occurrence of rebound angina during the nitrate-free intervals is a source of concern.


METHODS
We carried out a retrospective study of 606 patients to determine whether rebound angina occurred when conventional continuous nitrate administration was replaced by intermittent administration as part of a long-term therapy protocol for prior myocardial infarction. The subjects were receiving treatment for myocardial infarction and included 293 patients treated with nitrates (Nitrate group) and 313 patients who were not (No-nitrate group). The former included 186 patients who received intermittent nitrate administration (Intermittent group) and 107 patients who received continuous administration (Continuous group). The mean period of observation was 4.3 +/- 1.6 months.


RESULTS
There were no cases of rebound angina in the Intermittent group. Cardiac events occurred in one case in the No-nitrate group (0.3%), in 4 cases in the Continuous group (3.7%) and in 2 cases in the Intermittent group (1.1%). The incidence of cardiac events was thus significantly increased in the Continuous group compared to the No-nitrate group (p < 0.05; odds ratio 9.06; 95% CI 1.41-58.28). The Intermittent group did not significantly differ from the No-nitrate group in the incidence of cardiac events.


CONCLUSIONS
It is concluded that intermittent administration of nitrates does not cause rebound angina and is therefore safe. A randomized controlled trial is needed to find the long-term effect on cardiac events.
Ishikawa
K
K
First Department of Medicine, Kinki University School of Medicine, Osakasayama, Osaka.
Yamamoto
T
T
Kanamasa
K
K
Hayashi
T
T
Takenaka
T
T
Kimura
A
A
Miyataka
M
M
Yabushita
H
H
Kitayama
K
K
D000279:Administration, Cutaneous; D000284:Administration, Oral; D000368:Aged; D000787:Angina Pectoris / Q000517:prevention & control*; D002317:Cardiovascular Agents / Q000627:therapeutic use; D003329:Coronary Vasospasm / Q000453:epidemiology; D003692:Delayed-Action Preparations; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004361:Drug Tolerance; D017079:Exercise Tolerance; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000401:mortality / Q000517:prevention & control; D006801:Humans; D007548:Isosorbide Dinitrate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000401:mortality; D005996:Nitroglycerin / Q000008:administration & dosage / Q000627:therapeutic use*; D012008:Recurrence; D012189:Retrospective Studies; D016896:Treatment Outcome
D002317:Cardiovascular Agents; D003692:Delayed-Action Preparations; D005996:Nitroglycerin; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate