EditorialHow to RECOVER from RENAISSANCE? The significance of the results of RECOVER, RENAISSANCE, RENEWAL and ATTACH
Section snippets
The background in CHF
Plasma levels of inflammatory cytokines (including TNF) are raised in CHF patients, particularly in those in NYHA IV, cardiogenic shock or with cardiac cachexia (reviewed in [9]). Inflammatory cytokines are produced in the heart and can contribute to cardiac dysfunction [10], [11], they directly relate to poor peripheral perfusion [12], body composition [13], and weight changes [14], and the higher the plasma levels of parameters of inflammatory immune activation (like TNF, soluble TNF
Etanercept and infliximab in other disease states
Etanercept is a TNF receptor fusion protein [21], [22] which can be administered sub-cutaneously. The extracellular domain of the human p75 TNF receptor is fused to the Fc region of human IgG1. Infliximab is a chimeric (mouse/human) IgG1 monoclonal antibody that binds to both soluble and transmembrane TNF with high specificity and affinity [24]. Infliximab is given by intravenous application.
Anti-TNF therapies have recently been introduced for the management of rheumatoid arthritis and Crohn’s
The new studies: RENAISSANCE, RECOVER, RENEWAL, ATTACH
On this background, in 1996/1997 the RENAISSANCE, RECOVER and RENEWAL studies were designed. ATTACH followed somewhat later. In Oslo, Milton Packer stated that ATTACH was designed to be a pilot study for a subsequent morbidity/mortality study that would have been similar to the studies on etanercept [5]. The studies’ trial design, baseline patient characteristics and some of the main results are presented in Fig. 1, Fig. 2, and Table 1, Table 2, Table 3, Table 4, Table 5.
The etanercept studies
The king is dead – long live the king !?
Is the cytokine hypothesis [10] dead? We think reports of its death may be premature. Many, of course, have been discouraged by the results as documented above. We think they are not entirely surprising [39]. The cytokine hypothesis may not yet have been tested adequately in the right patients at the right doses !
The inclusion criteria of both trials were broad. In RENAISSANCE/RECOVER patients in NYHA II were allowed into the study. In ATTACH, the very low mortality in the placebo group (2% at
Acknowledgements
SDA is supported with the Vandervell Fellowship (London, UK) and a grant for “Applied Cachexia Research” by the Charité Medical School, Berlin, Germany. AJSC is supported by the Viscount Royston Trust, the British Heart Foundation and the Robert Luff Foundation.
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