The Effects of METhotrexate Therapy on the Physical Capacity of Patients With ISchemic Heart Failure: A Randomized Double-Blind, Placebo-Controlled Trial (METIS Trial)

Moreira, Daniel; Vieira, Jefferson L.; Gottschall, Carlos Antônio Mascia

doi:10.1016/j.cardfail.2009.06.439

Cited by 41 publications

(21 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Patients receiving adjuvant therapy with methotrexate had improvements in NYHA class, 6-min walk test, quality of life general scores, physical health score and accompanied decrease of inflammatory cytokines (TNF-a, IL-6 and CRP) when compared with baseline and control subjects. Although these results appeared to demonstrate that methotrexate, when added to conventional therapy, may provide additional benefits in the downregulation of inflammatory effects resulting in improvement in functional status, results were not consistent [45]. Therefore, results may be too preliminary to determine whether any therapeutic benefit through CRP lowering can be achieved with nonspecific immunomodulators in HF.…”

Section: Immunomodulatorscontrasting

confidence: 47%

Predicting therapeutic response in patients with heart failure: the story of C-reactive protein

Huynh

Tassell

Chow

2015

Expert Review of Cardiovascular Therapy

View full text Add to dashboard Cite

Heart failure continues to be a major public health burden in the USA. With markedly high rates of morbidity and mortality upon diagnosis, effective treatment and prognosis are critical in the management of chronic heart failure. Growing evidence now supports the hypothesis that inflammation plays a key role in the progression and worsening of heart failure. Of the various inflammatory mediators identified, C-reactive protein, an acute phase inflammatory marker, has been associated with poor prognosis in patients with heart failure. Several interventional studies have been investigated to explore C-reactive protein modulation and potential treatment options and health outcomes; however, further studies are warranted before C-reactive protein-targeted therapy may be recommended in the management of heart failure.

show abstract

Section: Immunomodulatorscontrasting

confidence: 47%

Predicting therapeutic response in patients with heart failure: the story of C-reactive protein

Huynh

Tassell

Chow

2015

Expert Review of Cardiovascular Therapy

View full text Add to dashboard Cite

show abstract

“…Moreover, methotrexate appears to reduce the incidence of myocardial infarction in patients with rheumatoid arthritis [99,100]. Given this evidence, one of the first studies to use methotrexate in ischemic heart disease was the METIS trial (METhotrexate Therapy Effects in the Physical Capacity of Patients With ISchemic Heart Failure trial), which evaluated low-dose methotrexate in patients with ischemic heart failure (HF) and showed a nonsignificant trend toward improved functional class [101]. Currently, there are two studies aimed at evaluating the use of methotrexate in ischemic heart disease in different situations.…”

Section: Methotrexate and Other Immunomodulating Drugsmentioning

confidence: 99%

Role of Vascular Inflammation in Coronary Artery Disease: Potential of Anti-inflammatory Drugs in the Prevention of Atherothrombosis

Moreira

Silva

Vieira

et al. 2014

Am J Cardiovasc Drugs

Self Cite

100

View full text Add to dashboard Cite

Coronary artery disease (CAD) and acute myocardial infarction (AMI) are inflammatory pathologies, involving interleukins (ILs), such as IL-1β, IL-6 and tumor necrosis factor (TNF)-α, and acute phase proteins production, such as for C reactive protein (CRP). The process begins with retention of low-density lipoprotein (LDL) and its oxidation inside the intima, with the formation of the "foam cells." Toll-like receptors and inflamassomes participate in atherosclerosis formation, as well as in the activation of the complement system. In addition to innate immunity, adaptive immunity is also associated with atherosclerosis through antigen-presenting cells, T and B lymphocytes. AMI also increases the expression of some ILs and promotes macrophage and lymphocyte accumulation. Reperfusion increases the expression of anti-inflammatory ILs (such as IL-10) and generates oxygen free radicals. Although CAD and AMI are inflammatory disorders, the only drugs with anti-inflammatory effect so far widely used in ischemic heart disease are aspirin and statins. Some immunomodulatory or immunosuppressive promising therapies, such as cyclosporine and colchicine, may have benefits in CAD. Methotrexate also has potential cardioprotective anti-inflammatory effects, through increased adenosine levels. The TETHYS trial (The Effects of mETHotrexate Therapy on ST Segment Elevation MYocardial InfarctionS trial) will evaluate low-dose methotrexate in ST elevation AMI. The CIRT (Cardiovascular Inflammation Reduction Trial), in turn, will evaluate low-dose methotrexate in patients with a high prevalence of subclinical vascular inflammation. The CANTOS (The Canakinumab Antiinflammatory Thrombosis Outcomes Study) will evaluate canakinumab in patients with CAD and persistently elevated CRP. The blockage of other potential targets, such as the IL-6 receptor, CC2 chemokine receptor and CD20, could bring benefits in CAD.

show abstract

“…54 Other smaller trials using intravenous immunoglobulin and methotrexate have yielded either mixed results or no benefit. [55][56][57] Another agent, colchicine, was used (n=277) in a blinded study of stable patients with HF, and although it reduced serum proinflammatory cytokines, there was no effect on any clinical indices. 58 With the exception of perhaps pentoxifylline, these nonspecific anti-inflammatory compounds showed little efficacy in chronic HF.…”

Section: Targeting General Inflammation In Chronic Hfmentioning

confidence: 99%

Chronic Heart Failure and Inflammation

Dick

Epelman

2016

Circulation Research

489

331

View full text Add to dashboard Cite

As a greater proportion of patients survive their initial cardiac insult, medical systems worldwide are being faced with an ever-growing need to understand the mechanisms behind the pathogenesis of chronic heart failure (HF). There is a wealth of information about the role of inflammatory cells and pathways during acute injury and the reparative processes that are subsequently activated. We discuss the different causes that lead to chronic HF development and how the sum of initial inflammatory and reparative responses only sets the trajectory for disease progression. Unfortunately, comparatively little is known about the contribution of the immune system once the trajectory has been set, and chronic HF has been established—which clinically represents the majority of patients. It is known that chronic HF is associated with circulating inflammatory cytokines that can predict clinical outcomes, yet the causative role inflammation plays in disease progression is not well defined, and the majority of clinical trials that target aspects of inflammation in patients with chronic HF have largely been negative. This review will present what is currently known about inflammation in chronic HF in both humans and animal models as a means to highlight the gap in our knowledge base that requires further examination.

show abstract

The Effects of METhotrexate Therapy on the Physical Capacity of Patients With ISchemic Heart Failure: A Randomized Double-Blind, Placebo-Controlled Trial (METIS Trial)

Cited by 41 publications

References 32 publications

Predicting therapeutic response in patients with heart failure: the story of C-reactive protein

Predicting therapeutic response in patients with heart failure: the story of C-reactive protein

Role of Vascular Inflammation in Coronary Artery Disease: Potential of Anti-inflammatory Drugs in the Prevention of Atherothrombosis

Chronic Heart Failure and Inflammation

Contact Info

Product

Resources

About