title: Comparison of the degree of hemodynamic tolerance during intravenous infusion of nitroglycerin versus nicorandil in patients with congestive heart failure.
abstract: BACKGROUND
  Continuous exposure to organic nitrates is associated with substantial tachyphylaxis. This study compares the development of tolerance during continuous intravenous treatment with nitroglycerin versus nicorandil over a 24-hour period.
  
  
  RESULTS
  Twenty patients with congestive heart failure and pulmonary capillary wedge pressure (PCWP) > or = 18 mm Hg were randomly assigned to nitroglycerin or nicorandil in a double-blind, crossover study. Doses were titrated to obtain a reduction of PCWP of at least 30% and then maintained. The mean pretreatment PCWP for nitroglycerin was 25.4 +/- 6.7 mm Hg, decreasing to 19.0 +/- 6.8 mm Hg at 24 hours. The values for nicorandil were 24.3 +/- 6.3 mm Hg and 15.6 +/- 4.5 mm Hg, respectively. Between-treatment difference was significant (p < 0.01). The difference between the minimal PCWP value and the 24-hour PCWP value for nitroglycerin was 5.1 mm Hg vs 1.4 mm Hg for nicorandil (p < 0.005). The mean systemic vascular resistance was 1418 +/- 355 dynes.sec.cm-5 before nitroglycerin infusion, decreasing to 1312 +/- 353 dynes.sec.cm-5 at 24 hours. Corresponding values for nicorandil were 1420 +/- 366 dynes.sec.cm-5 and 967 +/- 274 dynes.sec.cm-5. Between-treatment difference was significant (p = 0.005). Tachyphylaxis developed in 12 (60%) patients during nitroglycerin infusion versus three patients (15%) during nicorandil infusion.
  
  
  CONCLUSIONS
  This study demonstrates that intravenous nicorandil administration results in significantly less hemodynamic tolerance over a 24-hour period compared with nitroglycerin. This finding may represent a clinical advantage for nicorandil in the short-term treatment of patients with congestive heart failure.
authors.affiliation: Cardiovascular Division, Central Hospital in Rogaland, Norway.
authors.forename: A I
authors.initials: AI
authors.lastname: Larsen
authors.forename: L
authors.initials: L
authors.lastname: Gøransson
authors.forename: T
authors.initials: T
authors.lastname: Aarsland
authors.forename: J F
authors.initials: JF
authors.lastname: Tamby
authors.forename: K
authors.initials: K
authors.lastname: Dickstein
mesh_terms: D000368:Aged; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D020108:Nicorandil; D005996:Nitroglycerin / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D014665:Vasodilator Agents; D009536:Niacinamide; D020108:Nicorandil; D005996:Nitroglycerin