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| Year : 2004 | Volume
: 36
| Issue : 4 | Page : 257-258 |
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Anti TNF- therapy in congestive heart failure
Shalini Gupta , CD Tripathi
Department of Pharmacology, VMMC and Safdarjung Hospital, New Delhi - 110029, India
Correspondence Address:
Department of Pharmacology, VMMC and Safdarjung Hospital, New Delhi - 110029, India
[email protected]
How to cite this article:
Gupta S, Tripathi C D. Anti TNF- therapy in congestive heart failure. Indian J Pharmacol 2004;36:257-8 |
Sir,
The review “Anti TNF-a strategy: Present status of this therapeutic paradigm” describes the role of TNF-a antagonists as a potential therapeutic weapon in various clinical conditions. We appreciate the authors for enlightening us on the newer possible indications for this biological agent. The authors have reported that anti TNF-a therapy might benefit patients with congestive heart failure (CHF), and it is likely that official indications for anti TNF-a therapy would increase to include CHF. It is true that serum levels of tumor necrosis factor alpha (TNF-a) are elevated in patients with heart failure and these elevated levels contribute directly to progression of CHF. TNF-a also has established negative inotropic effects. These facts indicating that TNF-a is a deleterious factor in heart failure generated a lot of enthusiasm for the use of anti-TNF-a therapy in the management of heart failure. Several in vitro and in vivo experiments also demonstrated that TNF-a blocking therapy might improve cardiovascular function by reversing some of the deleterious effects of TNF-a. However, clinical trials of TNF-a antagonists for treatment of heart failure have reported controversial results.
Two TNF-a antagonists, Etanercept and Infliximab are approved for clinical use in rheumatoid arthritis and Crohn's disease. Despite the encouraging results of initial small pilot trials with etanercept,[1],[2] the results of large-scale multi-center trials[3],[4] do not demonstrate any clinical benefits and in-fact suggests that TNF-a blocking therapy might adversely affect the course of patients with CHF in a dose dependent manner. The reason why this TNF-a antagonism adversely affects the clinical status in CHF is not clear. It has been suggested that etanercept by making complexes with TNF-a, retains it within the circulation for a longer duration, which may prolong the exposure of cardiac tissue to TNF-a leading to cardiac toxicity.[5] Infliximab can cause cell lysis in the presence of complement when exposed to cells expressing transmembrane TNF-a, an effect that would be undesirable if it occurred in cardiomyocytes in patients with CHF.[6]
Animal experiments and early clinical studies of blocking TNF in patients of heart failure demonstrated promising results. However, large scale, randomized, placebo controlled trials of TNF-a antagonists for treatment of heart failure were stopped early because they failed to demonstrate an improvement in clinical status of heart failure or mortality. The discouraging results of clinical trials and case reports have important pragmatic implications. The prescribing information for etanercept and infliximab now suggests that physicians should exercise caution in the use of these agents in patients with heart failure.
| » References | |  |
| 1. | Deswal A, Bozkurt B, Seta Y, Parilti-Eiswirth S, Hayes FA, Blosch C, et al. Safety and efficacy of a soluble P75 tumor necrosis factor receptor (Enbrel, etanercept) in patients with advanced heart failure. Circulation 1999;99:3224-6.  [PUBMED] [FULLTEXT] |
| 2. | Bozkurt B, Torre-Amione G, Warren MS, Whitmore J, Soran OZ, Feldman AM, et al. Results of targeted antitumor necrosis factor therapy with etanercept (ENBREL) in patients with advanced heart failure. Circulation 2001;103:1044-7. [PUBMED] [FULLTEXT] |
| 3. | Anker SD, Coats AJ. How to RECOVER from RENAISSANCE? The significance of the results of RECOVER, RENAISSANCE, RENEWAL and ATTACH. Int J Cardiol 2002;86:123-30. [PUBMED] [FULLTEXT] |
| 4. | Chung ES, Packer M, Lo KH, Fasanmade AA, Willerson JT. Randomized, double-blind, placebo-controlled, pilot trial of Infliximab, a chimeric monoclonal antibody to tumor necrosis factor-?, in patients with moderate-to-sever heart failure. Results of the anti TNF therapy against congestive heart failure (ATTACH) trial. Circulation 2003;107:3133-40. |
| 5. | Aderka D, Engelmann H, Maor Y Brake-busch C, Wallach D. Stabilisation of bioactivity of tumor necrosis factor by its soluble receptors. J Exp Med 1992;175:323-9. |
| 6. | Scallon BJ, Moore MA, Trinh H, Knight DM, Ghrayeb J. Chimeric anti-TNF-alpha monoclonal antibody cA2 binds recombinant transmembrane TNF-alpha and activates immune effector functions. Cytokine 1995;7:251-9. [PUBMED] [FULLTEXT] |
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