Ursodeoxycholic acid in patients with chronic heart failure: a double-blind, randomized, placebo-controlled, crossover trial.
OBJECTIVE
This study sought to assess the effects of ursodeoxycholic acid (UDCA) on endothelial function and inflammatory markers in patients with chronic heart failure (CHF).


BACKGROUND
Endothelial dysfunction is commonly observed in patients with CHF, and it contributes to the limitation in exercise capacity that accompanies this condition. Bacterial lipopolysaccharide may trigger proinflammatory cytokine release and promote further endothelial dysfunction. UDCA, a bile acid used in the treatment of cholestatic liver disease, has anti-inflammatory and cytoprotective properties and may contribute to the formation of mixed micelles around lipopolysaccharide. These properties may help to improve peripheral blood flow in patients with CHF.


METHODS
We performed a prospective, single-center, double-blind, randomized, placebo-controlled crossover study of UDCA in 17 clinically stable male patients with CHF (New York Heart Association functional class II/III, left ventricular ejection fraction <45%). Patients received in random order 500 mg UDCA twice daily for 4 weeks and placebo for another 4 weeks. The primary endpoint was post-ischemic peak peripheral arm blood flow as assessed by strain-gauge plethysmography.


RESULTS
Sixteen patients completed the study. UDCA was well tolerated in all patients. Compared with placebo, UDCA improved peak post-ischemic blood flow in the arm (+18%, p = 0.038), and a trend for improved peak post-ischemic blood flow in the leg was found (+17%, p = 0.079). Liver function improved: compared with placebo, levels of γ-glutamyl transferase, aspartate transaminase, and soluble tumor necrosis factor α receptor 1 were lower after treatment with UDCA than after placebo (all p < 0.05). There was no change in 6-min walk test or New York Heart Association functional class, and levels of tumor necrosis factor α and interleukin-6 were unchanged or increased compared with placebo.


CONCLUSIONS
UDCA is well tolerated in patients with CHF. UDCA improves peripheral blood flow and is associated with improved markers of liver function.
Applied Cachexia Research, Department of Cardiology, Charité Medical School, Campus Virchow-Klinikum, Berlin, Germany. stephan.von.haehling@web.de.
Stephan
S
von Haehling
Joerg C
JC
Schefold
Ewa A
EA
Jankowska
Jochen
J
Springer
Ali
A
Vazir
Paul R
PR
Kalra
Anja
A
Sandek
Günter
G
Fauler
Tatjana
T
Stojakovic
Michael
M
Trauner
Piotr
P
Ponikowski
Hans-Dieter
HD
Volk
Wolfram
W
Doehner
Andrew J S
AJ
Coats
Philip A
PA
Poole-Wilson
Stefan D
SD
Anker
D000368:Aged; D001647:Bile Acids and Salts / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001783:Blood Flow Velocity / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D017079:Exercise Tolerance / Q000187:drug effects*; D005500:Follow-Up Studies; D006225:Hand / Q000098:blood supply; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D007866:Leg / Q000098:blood supply; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D010991:Plethysmography; D011446:Prospective Studies; D013318:Stroke Volume; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage*
D001647:Bile Acids and Salts; D015415:Biomarkers; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D014580:Ursodeoxycholic Acid