Effects of 5′-Phosphodiesterase Four-Week Long Inhibition With Sildenafil in Patients With Chronic Heart Failure: A Double-Blind, Placebo-Controlled Clinical Trial

Abstract Background The effects of chronic inhibition of 5′-phosphodiesterase with sildenafil on functional capacity, ventilatory efficiency, oxygen uptake, pulmonary hypertension, and endothelial function in chronic heart failure (CHF) are unknown. Methods We conducted a randomized, double-blind, p...

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Bibliographic Details
Published in:Journal of cardiac failure 2008-04, Vol.14 (3), p.189-197
Main Authors: Behling, Alice, MD, ScD, Rohde, Luis E., MD, ScD, Colombo, Fernanda C., MD, ScD, Goldraich, Livia A., MD, Stein, Ricardo, MD, ScD, Clausell, Nadine, MD, PhD
Format: Article
Language:English
Subjects:
Administration, Oral
Adult
Aged
Area Under Curve
Cardiovascular
Chronic Disease
Dose-Response Relationship, Drug
Double-Blind Method
Drug Administration Schedule
Endothelial function
Exercise Test
Female
Follow-Up Studies
Heart Failure - diagnosis
Heart Failure - drug therapy
Heart Failure - enzymology
Heart Failure - mortality
Hemodynamics - drug effects
Hemodynamics - physiology
Humans
Male
Middle Aged
Multivariate Analysis
Phosphodiesterase Inhibitors - administration & dosage
Phosphoric Diester Hydrolases - metabolism
Piperazines - administration & dosage
Plethysmography
Probability
pulmonary hypertension
Purines - administration & dosage
Reference Values
Risk Assessment
Severity of Illness Index
sildenafil
Sildenafil Citrate
Sulfones - administration & dosage
Survival Rate
Time Factors
Treatment Outcome
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Summary:Abstract Background The effects of chronic inhibition of 5′-phosphodiesterase with sildenafil on functional capacity, ventilatory efficiency, oxygen uptake, pulmonary hypertension, and endothelial function in chronic heart failure (CHF) are unknown. Methods We conducted a randomized, double-blind, placebo-controlled trial to assess the acute (1 hour after 50 mg by mouth) and chronic (4 weeks after 50 mg 3 times per day by mouth) effects of sildenafil in outpatients with CHF. The outcomes were cardiopulmonary exercise test parameters (chronic effect), echocardiographic-derived pulmonary artery systolic pressure, and plethysmography-derived forearm blood flow (acute and chronic effects). Results Nineteen patients with CHF (48 ± 12 years) with an ejection fraction of 28% ± 6% were studied. Patients who received sildenafil (n = 11) showed improved maximal oxygen uptake, ventilatory efficiency, and oxygen uptake kinetics. Sildenafil decreased pulmonary artery systolic pressure levels at 60 minutes and at 4 weeks compared with changes after placebo ( P = .004 for group and time interaction). Improvement in ventilatory efficiency was positively associated with reductions in pulmonary artery systolic pressure. Patients allocated to placebo demonstrated a trend toward decreased forearm blood flow after reactive hyperemia, whereas this remained unchanged in patients allocated to sildenafil. Conclusions Sildenafil administration for 4 weeks in stable outpatients with CHF improves functional capacity, ventilatory efficiency, oxygen uptake kinetics, and pulmonary hypertension. These effects may be mediated in part by improvements in endothelial function.
ISSN:1071-9164
1532-8414
DOI:10.1016/j.cardfail.2007.11.006