PDE5-Inhibition With Sildenafil in Chronic Heart Failure
Summary
To test the hypothesis that long-term PDE5-inhibition by overexpressing the nitric oxide pathway is beneficial in chronic heart failure patients.
Double-blind and placebo-controlled trial. Primary end-points: quality of life and exercise performance
Description
In chronic heart failure (CHF), endothelial function (EF) deterioration and muscle underperfusion elicit ergoreflex exercise oversignaling, hyperventilation and breathlessness. PDE5 inhibition, by improving EF, might be beneficial. We tested this hypothesis in a long-term therapeutic trial. CHF patients were randomly assigned to placebo (23 cases, group 1) or sildenafil (23 cases, group 2) in addition to their current antifailure therapy, for 6 months. In group 2 and not in group 1, assessments at 3 and 6 months showed the following changes: reduction of systolic pulmonary artery pressure (-25.2 and –29.0 %), ergoreflex effect on ventilation (-66.6 and -72.5%), ventilation to CO2 production slope (VE/VCO2, -14.0 and -16.0%) and breathlessness (-29.6 and -27.1%); increase of brachial artery flow-mediated dilatation (FMD, +57.6 and +67.0%), peak exercise O2 uptake (peak VO2, +25.0 and +26.3%) and ratio of VO2 to work rate changes (VO2WR, +20.7 and +22.0%). These changes were significant at p<0.01. In group 2 and not in group 1, a significant correlation was found, at 3 and 6 months, between changes in FMD and those in ergoreflex VE. Changes in ergoreflex correlated with those in peak VO2 and VE/VCO2 slope. No remarkable side effects were noted, but flushing in 3 patients.
In CHF, benefits of sildenafil are sustained and consist of improvement in EF, modulation in ergoreflex signaling, attenuation in exercise hyperventilation and breathlessness, increase in aerobic efficiency and exercise performance. Thus, sildenafil can affect peripheral mechanisms of breathlessness and may be viewed as an effective and safe adjunct to the therapeutic armamentarium of CHF.
Study Design
Allocation: Randomized, Control: Placebo Control, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment
Conditions
Heart Failure
Intervention
sildenafil
Location
Marco Guazzi, MD, PhD University of Milano
Milano
Italy
20141
Status
Completed
Source
University of Milan
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00407446
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Heart Failure
A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION.
Cardiomegaly
Enlargement of the HEART, usually indicated by a cardiothoracic ratio above 0.50. Heart enlargement may involve the right, the left, or both HEART VENTRICLES or HEART ATRIA. Cardiomegaly is a nonspecific symptom seen in patients with chronic systolic heart failure (HEART FAILURE) or several forms of CARDIOMYOPATHIES.
Heart Failure, Diastolic
Heart failure caused by abnormal myocardial relaxation during DIASTOLE leading to defective cardiac filling.
Heart Failure, Systolic
Heart failure caused by abnormal myocardial contraction during SYSTOLE leading to defective cardiac emptying.
Cardiotonic Agents
Agents that have a strengthening effect on the heart or that can increase cardiac output. They may be CARDIAC GLYCOSIDES; SYMPATHOMIMETICS; or other drugs. They are used after MYOCARDIAL INFARCT; CARDIAC SURGICAL PROCEDURES; in SHOCK; or in congestive heart failure (HEART FAILURE).
Clinical Trials
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PubMed Articles
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