Dose requirements and hemodynamic effects of transdermal nitroglycerin compared with placebo in patients with congestive heart failure.

Abstract

The dose requirements and duration of effect of transdermal nitroglycerin in patients with heart failure are not clearly established. In a 1st series of 8 patients with chronic heart failure transdermal nitroglycerin ws given in incremental doses until pulmonary capillary wedge pressure fell at least 30% within 4 h in 3 consecutive patients. A single dose of 60 mg/24 h (120 cm2) was the minimal effective dose. Transdermal nitroglycerin or placebo was then given as a single application of 60 mg/24 h in random double-blind fashion to 15 additional patients with heart failure (8 received transdermal nitroglycerin and 7 received placebo); hemodynamics were monitored for up to 24 h. After administration of transdermal nitroglycerin, the control pulmonary capillary wedge pressure of 22 .+-. 7 mm Hg fell by 6 .+-. 6 mm Hg at 2 h (P < 0.05) and reached maximal reduction of 8 .+-. 6 mm Hg (P < 0.01) at 4 h. The reduction in wedge pressure remained significant through 12 h but was no longer statistically significant by 18 h after administration of the drug. Transdermal nitroglycerin also significantly reduced pulmonary arterial and right atrial pressures and pulmonary vascular resistance from 4 through 12 h but did not affect systemic hemodynamics. No significant hemodynamic changes occurred after administration of placebo. Thus transdermal nitroglycerin is an effective vasodilator in patients with heart failure, but a dose of at least 60 mg/24 h is needed. Even with this dose, hemodynamic effects do not last beyond 18 h, suggesting altered absorption or development of tolerance.