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 tolerance during continuous intravenous treatment with nitroglycerin versus nicorandil over a 24-hour period. Methods and Results Twenty patients with congestive heart failure and pulmonary capillary wedge pressure (PCWP) ≥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. Conclusion 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. (Am Heart J 1997;134:435-41.)