title: Long-term nitrate treatment increases cardiac events in patients with healed myocardial infarction. Secondary Prevention Group.
abstract: 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.
authors.affiliation: First Department of Medicine, Kinki University, School of Medicine, Osaka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ishikawa
authors.forename: K
authors.initials: K
authors.lastname: Kanamasa
authors.forename: I
authors.initials: I
authors.lastname: Ogawa
authors.forename: T
authors.initials: T
authors.lastname: Takenaka
authors.forename: T
authors.initials: T
authors.lastname: Naito
authors.forename: N
authors.initials: N
authors.lastname: Kamata
authors.forename: T
authors.initials: T
authors.lastname: Yamamoto
authors.forename: S
authors.initials: S
authors.lastname: Nakai
authors.forename: J
authors.initials: J
authors.lastname: Hama
authors.forename: M
authors.initials: M
authors.lastname: Oyaizu
authors.forename: A
authors.initials: A
authors.lastname: Kimura
authors.forename: K
authors.initials: K
authors.lastname: Yamamoto
authors.forename: N
authors.initials: N
authors.lastname: Aso
authors.forename: M
authors.initials: M
authors.lastname: Arai
authors.forename: H
authors.initials: H
authors.lastname: Yabushita
authors.forename: Y
authors.initials: Y
authors.lastname: Katori
mesh_terms: 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*
chemical_list: D009566:Nitrates; D014665:Vasodilator Agents; D005996:Nitroglycerin; D007548:Isosorbide Dinitrate