The nonspecific anti-inflammatory therapy with methotrexate for patients with chronic heart failure

• Published in: The American heart journal Vol. 151; no. 1; pp. 62 - 68
• Main Authors: Gong, Kaizheng, Zhang, Zhengang, Sun, Xiaonin, Zhang, Xin, Li, Aihua, Yan, Junfeng, Luo, Qiuping, Gao, Yang, Feng, Yiliang
• Format: Journal Article
• Language: English
• Published: United States Mosby, Inc 2006; Elsevier Limited
• Subjects: Angina pectoris; Anti-Inflammatory Agents - adverse effects; Anti-Inflammatory Agents - therapeutic use; Cardiovascular disease; Chronic Disease; Cytokines; Cytokines - blood; Drug therapy; Female; Heart attacks; Heart Failure - blood; Heart Failure - drug therapy; Humans; Inflammation Mediators - blood; Male; Methotrexate - adverse effects; Methotrexate - therapeutic use; Middle Aged; Prospective Studies; Single-Blind Method
• ISSN: 0002-8703; 1097-6744
• DOI: 10.1016/j.ahj.2005.02.040

Inflammatory mediators play an important role in the pathogenesis of chronic heart failure (CHF). Methotrexate (MTX) is used in the treatment of inflammatory-mediated diseases (eg, rheumatoid arthritis) because it modulates the expression of numerous inflammatory cytokines. However, no studies have assessed the effects of MTX on plasma levels of inflammatory mediators in patients with CHF. In a prospective, randomized, placebo-controlled, single-blind study, 71 patients receiving conventional treatment were randomly allocated to either MTX group (7.5 mg once a week, n = 35) or placebo group (n = 36) with a follow-up of 12 weeks. The effects of MTX on plasma cytokine expression, left ventricular ejection fraction, left ventricular end-diastolic dimension, New York Heart Association (NYHA) functional class, 6-minute walk test distance, and quality of life (QOL) were determined in patients with CHF. Sixty-two patients completed the study. The circulating levels of inflammatory mediators in patients with CHF were markedly elevated compared with healthy controls ( P ≤ .002). Methotrexate (n = 30) reduced plasma levels of tumor necrosis factor α (−15.6%, P < .05), interleukin 6 (−21.8%, P < .01), monocyte chemoattractant protein-1 (−22.6%, P < .01), soluble intercellular adhesion molecule-1 (−19.2%, P < .05), and C-reactive protein (−27.2%, P < .01) compared with baseline. Furthermore, interleukin 10 (15.8 %, P < .05) and soluble IL-1 receptor antagonist (36.1%, P < .01) expression was increased, whereas improvements in NYHA classification, 6-minute walk test distance, and QOL were found compared with baseline. Monocyte chemoattractant protein-1 expression was lower and soluble IL-1 receptor antagonist expression higher in the MTX than placebo group (n = 32). Furthermore, the left ventricular ejection fraction, left ventricular end-diastolic dimension, and incidence of main adverse cardiac events between the 2 groups were similar. These results suggest that the addition of MTX to conventional therapy for CHF has significant anti-inflammatory effects and improves NYHA functional class, 6-minute walk test distance, and QOL.