COMPARISON OF THE DEGREE OF HEMODYNAMIC TOLERANCE DURING INTRAVENOUS-INFUSION OF NITROGLYCERIN VERSUS NICORANDIL IN PATIENTS WITH CONGESTIVE-HEART-FAILURE

Background Continuous exposure to organic nitrates is associated with substantial tachyphylaxis. This study compares the development of tole rance during continuous intravenous treatment with nitroglycerin versu s nicorandil over a 24-hour period, Methods and Results Twenty patient s with congestive heart failure and pulmonary capillary wedge pressure (PCWP) greater than or equal to 18 mm Hg were randomly assigned to ni troglycerin or nicorandil in a double-blind, crossover study. Doses we re titrated to obtain a reduction of PCWP of at least 30% and then mai ntained. 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 n icorandil were 24.3 +/- 6.3 mm Hg and 15.6 +/- 4.5 mm Hg, respectively . Between-treatment difference was significant (p < 0.01). The differe nce between the minimal PCWP value and the 24-hour PCWP value For nitr oglycerin was 5.1 mm Hg vs 1.4 mm Hg for nicorandil (p < 0.005), The m ean systemic vascular resistance was 1418 +/- 355 dynes.sec.cm(-5) bef ore nitroglycerin infusion, decreasing to 1312 +/- 353 dynes.sec.cm(-5 ) at 24 hours. Corresponding values for nicorandil were 1420 +/- 366 d ynes.sec.cm(-5) and 967 +/- 274 dynes.sec.cm(-5). Between-treatment di fference was significant (p = 0.005). Tachyphylaxis developed in 12 (6 0%) patients during nitroglycerin infusion versus three patients (15%) during nicorandil infusion. Conclusion This study demonstrates that i ntravenous nicorandil administration results in significantly less hem odynamic 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.