Ursodeoxycholic Acid in Patients With Chronic Heart Failure A Double-Blind, Randomized, Placebo-Controlled, Crossover Trial

作者：von Haehling Stephan^*; Schefold Joerg C; Jankowska Ewa A; Springer Jochen; Vazir Ali; Kalra Paul R; Sandek Anja; Fauler Guenter; Stojakovic Tatjana; Trauner Michael; Ponikowski Piotr; Volk Hans Dieter; Doehner Wolfram; Coats Andrew J S; Poole Wilson Philip A; Anker Stefan D

来源：Journal of the American College of Cardiology, 2012, 59(6): 585-592.

DOI：10.1016/j.jacc.2011.10.880

• blood flow
• cytokines
• heart failure
• inflammation
• ursodeoxycholic acid

Objectives This study sought to assess the effects of ursodeoxycholic acid (UDCA) on endothelial function and inflammatory markers in patients with chronic heart failure (CHF). %26lt;br%26gt;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. %26lt;br%26gt;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 %26lt;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. %26lt;br%26gt;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 gamma-glutamyl transferase, aspartate transaminase, and soluble tumor necrosis factor alpha receptor 1 were lower after treatment with UDCA than after placebo (all p %26lt; 0.05). There was no change in 6-min walk test or New York Heart Association functional class, and levels of tumor necrosis factor alpha and interleukin-6 were unchanged or increased compared with placebo. %26lt;br%26gt;Conclusions UDCA is well tolerated in patients with CHF. UDCA improves peripheral blood flow and is associated with improved markers of liver function.

• 出版日期2012-2-7
• 单位河北医科大学