The Effects of METhotrexate Therapy on the Physical Capacity of Patients With ISchemic Heart Failure: A Randomized Double-Blind, Placebo-Controlled Trial (METIS Trial)
Received 7 April 2009; received in revised form 20 June 2009; accepted 24 June 2009. published online 06 August 2009.
Abstract
Background
The cytokine hypothesis suggests that there is an association between chronic heart failure (CHF) and inflammation. Methotrexate could improve CHF patients' clinical status, especially those with ischemic etiology.
Methods and Results
METIS is a randomized, double-blinded trial studying 50 patients with ischemic CHF given methotrexate (7.5mg) or placebo, plus folic acid (5mg), for 12 weeks. The primary end point was the difference in 6-minute walk test (6MWT) distance before and after treatment. We also evaluated functional class (NYHA), Short-Form 36 protocol quality of life, C-reactive protein (CRP), incidence of adverse effects, and the combined incidence of death, myocardial infarction, stroke, hospitalization, and need for myocardial revascularization. There was no significant difference between groups in distance covered in the 6MWT: the methotrexate group improved by 24.5±39.5m, the placebo group by 21.3±43.7m (P=.80). The NYHA scores improved in 66.7% of the methotrexate group patients and in 50.0% of the placebo group (P=.2). SF-36 scores indicated improved mental health in the placebo group. There were no significant differences in CRP levels, the combined outcome, or adverse events.
Conclusions
These results show that the methotrexate group tended toward improved NYHA scores and that there were no significant changes in 6MWT results or secondary assessments.
Instituto de Cardiologia do Rio Grande do Sul, Porte Alegro, Brazil
Reprint requests: Daniel Medeiros Moreira, Instituto de Cardiologia do Rio Grande do Sul – Fundação Universitária de Cardiologia; Rua Princesa Isabel, 390, Santana, Porto Alegre, RS – Brazil CEP: 90620-001.
Supported by FAPIC – Fundação de Amparo a Pesquisa do Instituto de Cardiologia do Rio Grande do Sul – Institutional financial support.
ABSTRACT