Sustained beneficial hemodynamic effects of low transdermal nitroglycerin doses compared with placebo in patients with congestive heart failure

In an attempt to resolve some of the controversies concerning the dose requirements and duration of effects of transdermal nitroglycerin (NTG) in patients with heart failure (CHF), the short‐term hemodynamic responses to transdermal NTG, in a 20 cm2 self‐adhesive patch (10 mg/24 h), were evaluated in 10 patients with severe chronic CHF using a randomized, within‐patient, double‐blind, placebo‐controlled cross‐over trial. Serial hemodynamic measurements over 24 h revealed sustained effects that began 1 h after the application of nitroglycerin patch and fully persisted throughout the study. The peak effect occurred at 4 h with the pulmonary capillary wedge pressure decreasing from 33.7±8.4 to 21.4±9 mmHg (mean ± SD) (p>0.05) and the cardiac index increasing from 2.5±0.6 to 3±0.6 1/min/m2 (p>0.01). Transdermal nitroglycerin also significantly reduced pulmonary arterial and right atrial pressures (from 43.5±9.5 to 31 ±11.4 and from 7.4±6.6 to 3.8±4.7 at peak effect, respectively) as well as pulmonary and systemic vascular resistances (from 10.7±6.6 to 6.5±3.2 and from 26.2±5.1 to 22.5±5.7, respectively). There was no change in heart rate or systemic arterial pressure. These beneficial hemodynamic responses persisted for 24 h. No rebound deterioration occurred upon withdrawal of the nitroglycerin. No significant hemodynamic changes occurred during placebo treatment period. Thus, low doses (10 mg/24 h) of transdermal nitroglycerin induce significant hemodynamic benefit that is sustained for 24 h in patients with heart failure. The lack of attenuation of the effects with this dose suggests that larger doses may in fact promote the development of tolerance.