da-8159 and Chronic-Disease

Impaired nitric oxide-mediated pulmonary vascular tone is commonly found in heart failure with reduced ejection fraction (HFrEF), and is associated with derangement of left ventricular (LV) hemodynamics and decreased exercise capacity, which may be reversed by PDE5 inhibitor. This study investigated the effects of a new, long-acting PDE5 inhibitor on LV hemodynamics and exercise capacity in HFrEF.. Patients with chronic HFrEF on optimal medical therapy for >30 days before enrollment were randomly assigned to placebo or udenafil at a dose of 50mg 2x/day for the first 4 weeks followed by 100mg 2x/day for the next 8 weeks. All patients underwent cardiopulmonary exercise echocardiography before and after the 12-week treatment.. Improvement of subjective functional capacity was more frequently reported in the udenafil group (P = 0.002). Also, a higher increase in peak VO2 (Δpeak VO2, 21.6% (6.9 ~ 106.4%) vs 1.9% (-15.7 ~ 21.0%) in the placebo group, P = 0.04) and a larger decrease in ventilatory efficiency were observed in the udenafil group (Δ-6.4 ± 9.7 vs Δ1.9 ± 12.1 in the placebo group, P = 0.03). Regarding LV systolic function, the extent of increment in LV ejection fraction was significantly greater in the udenafil group (6.6 ± 6.4% vs 2.3 ± 4.8% in the placebo group, P = 0.02). In the udenafil group, an echocardiographic surrogate of LV filling pressure was more prominently decreased (P = 0.006) along with a significant reverse remodeling of left atrial volume index (57 ± 25mL at baseline to 44 ± 23 at 12th week, P = 0.04) and a progressive fall in B-type natriuretic peptide level (589 ± 679pg/mL at baseline to 220 ± 225pg/mL at 12th week, P < 0.001), indicating LV diastolic function improvement. Udenafil was well tolerated without excess of adverse events compared to placebo.. Udenafil improves LV systolic/diastolic functions and exercise capacity in conjunction with established conventional pharmacotherapy, without significant adverse events in HFrEF.

Topics: Aged; Chronic Disease; Double-Blind Method; Exercise Test; Exercise Tolerance; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Oxygen Consumption; Phosphodiesterase 5 Inhibitors; Prospective Studies; Pyrimidines; Sulfonamides; Ultrasonography; Ventricular Dysfunction, Left; Ventricular Function, Left

Over the last few years, the use of phosphodiesterase type 5 (PDE5) inhibitors has been expanded to management of various cardiovascular disorders beyond pulmonary arterial hypertension. This study is designed to investigate the ability of udenafil, a newly developed long-acting PDE5 inhibitor, to improve functional capacity and hemodynamic status in a cohort of chronic systolic heart failure (SHF) patients.. Stable, chronic SHF patients will be randomly assigned to placebo (26 patients) or udenafil at a dose of 50 mg twice per day (26 patients) for the first 4 weeks followed by 100 mg twice daily for the next 8 weeks. Eligibility criteria will be age ≥ 18 years, clinical diagnosis of chronic SHF with current New York Heart Association class II to IV symptoms, left ventricular ejection fraction ≤ 40%, and experience of at least one of following during the 12 months prior to study entry: hospitalization for decompensated heart failure, acute treatment with intravenous loop diuretics or hemofiltration, or pulmonary artery systolic pressure ≥ 40 mmHg on transthoracic echocardiography. Pharmacological therapy for SHF will be optimized in all patients at least 30 days before study entry. The primary outcome will be the change of maximal oxygen uptake, assessed by cardiopulmonary exercise testing. Secondary outcomes will include changes in ventilatory efficiency (minute ventilation/carbon dioxide production slope), left ventricular systolic and diastolic parameters, pulmonary artery systolic pressure, plasma concentration of brain natriuretic peptide, occurrence of mortality or hospitalization for heart failure, and the occurrence of any adverse event.. Unique identifier: NCT01646515.

Topics: Biomarkers; Cardiovascular Agents; Chronic Disease; Clinical Protocols; Double-Blind Method; Drug Administration Schedule; Exercise Test; Exercise Tolerance; Heart Failure, Systolic; Hemodynamics; Hospitalization; Humans; Natriuretic Peptide, Brain; Oxygen Consumption; Phosphodiesterase 5 Inhibitors; Prospective Studies; Pyrimidines; Recovery of Function; Republic of Korea; Research Design; Stroke Volume; Sulfonamides; Systole; Time Factors; Treatment Outcome; Ventricular Function, Left