Long-term nitrate treatment increases cardiac events in patients with healed myocardial infarction. Secondary Prevention Group.
BACKGROUND
Nitrates dilate coronary arteries, ameliorate myocardial ischemia, minimize left ventricular remodeling, and reduce mortality in patients with acute myocardial infarction. However, the effects of long-term treatment with nitrates on cardiac events in patients with healed myocardial infarction are not known.


RESULTS
A total of 1,002 patients with healed myocardial infarction (789 male and 213 female) were randomly divided into 2 groups: treatment with nitrates or nontreatment. The mean observation period was 18.0 +/- 19.9 months. Primary end points were nonfatal and fatal recurrent myocardial infarction, death from congestive heart failure, and sudden death. Baseline characteristics of the 2 groups were also compared to determine any effects on outcome. Among the 621 cases treated with nitrates, 41 cases (6.6%) experienced cardiac events during the observation period, whereas only 12 of the 381 cases that were not treated with nitrates (3.1%) had cardiac events. This difference was statistically significant (p < 0.05; odds ratio 2.17; 95% confidence interval 1.13-4.19). There were no differences in the incidence of noncardiac death or being lost to follow-up between the 2 groups. Although the precise mechanism of this increase in the occurrence of cardiac events by long-term treatment with nitrates is not clear, nitrate tolerance with possible rebound and neurohormonal effects may be involved.


CONCLUSIONS
Long-term treatment with nitrates increased cardiac events in patients with healed myocardial infarction.
Ishikawa
K
K
First Department of Medicine, Kinki University, School of Medicine, Osaka, Japan.
Kanamasa
K
K
Ogawa
I
I
Takenaka
T
T
Naito
T
T
Kamata
N
N
Yamamoto
T
T
Nakai
S
S
Hama
J
J
Oyaizu
M
M
Kimura
A
A
Yamamoto
K
K
Aso
N
N
Arai
M
M
Yabushita
H
H
Katori
Y
Y
D000368:Aged; D016757:Death, Sudden, Cardiac / Q000209:etiology*; D004311:Double-Blind Method; D004361:Drug Tolerance; D005260:Female; D006333:Heart Failure / Q000209:etiology*; D006801:Humans; D007548:Isosorbide Dinitrate / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000209:etiology; D009566:Nitrates / Q000008:administration & dosage*; D005996:Nitroglycerin / Q000008:administration & dosage*; D016017:Odds Ratio; D012008:Recurrence; D013997:Time Factors; D014665:Vasodilator Agents / Q000008:administration & dosage*
D009566:Nitrates; D014665:Vasodilator Agents; D005996:Nitroglycerin; D007548:Isosorbide Dinitrate