| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 1999;99:3224-3226.)
© 1999 American Heart Association, Inc.
Brief Rapid Communications |
Safety and Efficacy of a Soluble P75 Tumor Necrosis Factor Receptor (Enbrel, Etanercept) in Patients With Advanced Heart Failure
From the Winters Center for Heart Failure Research, Cardiology Section, Department of Medicine, Veterans Administration Medical Center, and Baylor College of Medicine, Houston, Tex; and Immunex Corp, Seattle, Wash (F.A.H., C.B.).
Background—Although previous studies suggested that TNF may contribute to heart failure progression, it is unclear whether antagonizing TNF is beneficial in heart failure patients.
Methods and Results—Eighteen NYHA class III heart failure patients were randomized into a double-blind dose-escalation study to examine the safety and potential efficacy of etanercept, a specific TNF antagonist (Enbrel). Patients received placebo (6 patients) or an escalating dose (1, 4, or 10 mg/m2) of etanercept (12 patients) given as a single intravenous infusion. Safety parameters and patient functional status were assessed at baseline and at days 1, 2, 7, and 14. There were no significant side effects or clinically significant changes in laboratory indices. There was, however, a decrease in TNF bioactivity and a significant overall increase in quality-of-life scores, 6-minute walk distance, and ejection fraction in the cohort that received 4 or 10 mg/m2 of etanercept; there was no significant change in these parameters in the placebo group.
Conclusions—A single intravenous infusion of etanercept was safe and well tolerated in patients with NYHA class III heart failure. These studies provide provisional evidence that suggests that etanercept is sufficient to lower levels of biologically active TNF and may lead to improvement in the functional status of patients with heart failure.
Key Words: tumor necrosis factor • heart failure • etanercept
This article has been cited by other articles:
 |
|
 |
|
  E. Chorianopoulos, M. Rosenberg, C. Zugck, J. Wolf, H. A. Katus, and N. Frey Decreased soluble TWEAK levels predict an adverse prognosis in patients with chronic stable heart failure Eur J Heart Fail, November 1, 2009; 11(11): 1050 - 1056. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Lockett, M. G. Goebl, and M. A. Harrington Transient membrane recruitment of IRAK-1 in response to LPS and IL-1{beta} requires TNF R1 Am J Physiol Cell Physiol, August 1, 2008; 295(2): C313 - C323. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Monden, T. Kubota, T. Tsutsumi, T. Inoue, S. Kawano, N. Kawamura, T. Ide, K. Egashira, H. Tsutsui, and K. Sunagawa Soluble TNF receptors prevent apoptosis in infiltrating cells and promote ventricular rupture and remodeling after myocardial infarction Cardiovasc Res, March 1, 2007; 73(4): 794 - 805. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. S. Hoare, E. J. Birks, C. Bowles, N. Marczin, and M. H. Yacoub In vitro endothelial cell activation and inflammatory responses in end-stage heart failure J Appl Physiol, November 1, 2006; 101(5): 1466 - 1473. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. S Schleithoff, A. Zittermann, G. Tenderich, H. K Berthold, P. Stehle, and R. Koerfer Vitamin D supplementation improves cytokine profiles in patients with congestive heart failure: a double-blind, randomized, placebo-controlled trial. Am. J. Clinical Nutrition, April 1, 2006; 83(4): 754 - 759. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Grundmann, I. Hoefer, S. Ulusans, N. van Royen, S. H. Schirmer, C. K. Ozaki, C. Bode, J. J. Piek, and I. Buschmann Anti-tumor necrosis factor-{alpha} therapies attenuate adaptive arteriogenesis in the rabbit Am J Physiol Heart Circ Physiol, October 1, 2005; 289(4): H1497 - H1505. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. G. Olsson, K. Swedberg, A. L. Clark, K. K. Witte, and J. G.F. Cleland Six minute corridor walk test as an outcome measure for the assessment of treatment in randomized, blinded intervention trials of chronic heart failure: a systematic review Eur. Heart J., April 2, 2005; 26(8): 778 - 793. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K L Hyrich, A J Silman, K D Watson, and D P M Symmons Anti-tumour necrosis factor {alpha} therapy in rheumatoid arthritis: an update on safety Ann Rheum Dis, December 1, 2004; 63(12): 1538 - 1543. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. W. Moe, J. Marin-Garcia, A. Konig, M. Goldenthal, X. Lu, and Q. Feng In vivo TNF-{alpha} inhibition ameliorates cardiac mitochondrial dysfunction, oxidative stress, and apoptosis in experimental heart failure Am J Physiol Heart Circ Physiol, October 1, 2004; 287(4): H1813 - H1820. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. L. Mann, J. J.V. McMurray, M. Packer, K. Swedberg, J. S. Borer, W. S. Colucci, J. Djian, H. Drexler, A. Feldman, L. Kober, et al. Targeted Anticytokine Therapy in Patients With Chronic Heart Failure: Results of the Randomized Etanercept Worldwide Evaluation (RENEWAL) Circulation, April 6, 2004; 109(13): 1594 - 1602. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. D Anker and S. von Haehling Inflammatory mediators in chronic heart failure: an overview Heart, April 1, 2004; 90(4): 464 - 470. [Full Text] [PDF]
|
|
|
|
|
|
P. Bahrmann, U. M. Hengst, B. M. Richartz, and H. R. Figulla Pentoxifylline in ischemic, hypertensive and idiopathic-dilated cardiomyopathy: effects on left-ventricular function, inflammatory cytokines and symptoms Eur J Heart Fail, March 1, 2004; 6(2): 195 - 201. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. E. Chapman and F. G. Spinale Extracellular protease activation and unraveling of the myocardial interstitium: critical steps toward clinical applications Am J Physiol Heart Circ Physiol, January 1, 2004; 286(1): H1 - H10. [Full Text] [PDF]
|
|
|
|
 |
|
 H. Tomasdottir, H. Hjartarson, A. Ricksten, C. Wasslavik, A. Bengtsson, and S.-E. Ricksten Tumor Necrosis Factor Gene Polymorphism Is Associated with Enhanced Systemic Inflammatory Response and Increased Cardiopulmonary Morbidity After Cardiac Surgery Anesth. Analg., October 1, 2003; 97(4): 944 - 949. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. J. Kwon, T. R. Cote, M. S. Cuffe, J. M. Kramer, and M M. Braun Case Reports of Heart Failure after Therapy with a Tumor Necrosis Factor Antagonist Ann Intern Med, May 20, 2003; 138(10): 807 - 811. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Mehra, P. A. Uber, and G. S. Francis Heart failure therapy at a crossroad: are there limits to the neurohormonal model? J. Am. Coll. Cardiol., May 7, 2003; 41(9): 1606 - 1610. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Pasic, W. C. Levy, and M. D. Sullivan Cytokines in Depression and Heart Failure Psychosom Med, March 1, 2003; 65(2): 181 - 193. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P A Henriksen and D E Newby Therapeutic inhibition of tumour necrosis factor {alpha} in patients with heart failure: cooling an inflamed heart Heart, January 1, 2003; 89(1): 14 - 18. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Pugh, R. D. Jones, T.H. Jones, and K. S. Channer Heart failure as an inflammatory condition: potential role for androgens as immune modulators Eur J Heart Fail, December 1, 2002; 4(6): 673 - 680. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.B. Felix, A. Staudt, and G. Baumann Immunoadsorption as a new therapeutic principle for treatment of dilated cardiomyopathy Eur. Heart J. Suppl., December 1, 2002; 4(suppl_I): I63 - I68. [Abstract] [PDF]
|
|
|
|
 |
|
 D. L. Mann Inflammatory Mediators and the Failing Heart: Past, Present, and the Foreseeable Future Circ. Res., November 29, 2002; 91(11): 988 - 998. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. CONDORELLI, C. MORISCO, M. V. G. LATRONICO, P. P. CLAUDIO, P. DENT, P. TSICHLIS, G. CONDORELLI, G. FRATI, A. DRUSCO, C. M. CROCE, et al. TNF-{alpha} signal transduction in rat neonatal cardiac myocytes: definition of pathways generating from the TNF-{alpha} receptor FASEB J, November 1, 2002; 16(13): 1732 - 1737. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. S. Bradham, G. Moe, K. A. Wendt, A. A. Scott, A. Konig, M. Romanova, G. Naik, and F. G. Spinale TNF-alpha and myocardial matrix metalloproteinases in heart failure: relationship to LV remodeling Am J Physiol Heart Circ Physiol, April 1, 2002; 282(4): H1288 - H1295. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. S. Bradham, B. Bozkurt, H. Gunasinghe, D. Mann, and F. G. Spinale Tumor necrosis factor-alpha and myocardial remodeling in progression of heart failure: a current perspective Cardiovasc Res, March 1, 2002; 53(4): 822 - 830. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. B. Felix, A. Staudt, M. Landsberger, Y. Grosse, V. Stangl, T. Spielhagen, G. Wallukat, K. D. Wernecke, G. Baumann, and K. Stangl Removal of cardiodepressant antibodies in dilated cardiomyopathy by immunoadsorption J. Am. Coll. Cardiol., February 20, 2002; 39(4): 646 - 652. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Fichtlscherer, L. Rossig, S. Breuer, M. Vasa, S. Dimmeler, and A. M. Zeiher Tumor Necrosis Factor Antagonism With Etanercept Improves Systemic Endothelial Vasoreactivity in Patients With Advanced Heart Failure Circulation, December 18, 2001; 104(25): 3023 - 3025. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Rosenberg, S. W. Martin, J. E. Seely, O. Kinstler, G. C. Gaines, K. Fukuzuka, J. Rose, T. Kohno, W. J. Boyle, A. Nelson, et al. Development of a novel, nonimmunogenic, soluble human TNF receptor type I (sTNFR-I) construct in the baboon J Appl Physiol, November 1, 2001; 91(5): 2213 - 2223. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Ishibashi, T. Shimada, Y. Murakami, N. Takahashi, T. Sakane, T. Sugamori, S. Ohata, S.-i. Inoue, Y. Ohta, K. Nakamura, et al. An inhibitor of inducible nitric oxide synthase decreases forearm blood flow in patients with congestive heart failure J. Am. Coll. Cardiol., November 1, 2001; 38(5): 1470 - 1476. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Adamopoulos, J. T. Parissis, and D. Th. Kremastinos A glossary of circulating cytokines in chronic heart failure Eur J Heart Fail, October 1, 2001; 3(5): 517 - 526. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Stamm, I. Friehs, D. B. Cowan, A. M. Moran, H. Cao-Danh, L. F. Duebener, P. J. del Nido, and F. X. McGowan Jr Inhibition of Tumor Necrosis Factor-{alpha} Improves Postischemic Recovery of Hypertrophied Hearts Circulation, September 18, 2001; 104 (2009): I-350 - I-355. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Deswal, N. J. Petersen, A. M. Feldman, B. G. White, and D. L. Mann Effects of Vesnarinone on Peripheral Circulating Levels of Cytokines and Cytokine Receptors in Patients With Heart Failure : A Report From the Vesnarinone Trial Chest, August 1, 2001; 120(2): 453 - 459. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Braunwald Congestive heart failure: a half century perspective Eur. Heart J., May 2, 2001; 22(10): 825 - 836. [PDF]
|
|
|
|
|
|
L. Dalla Libera, B. Ravara, A. Angelini, K. Rossini, M. Sandri, G. Thiene, G. Battista Ambrosio, and G. Vescovo Beneficial Effects on Skeletal Muscle of the Angiotensin II Type 1 Receptor Blocker Irbesartan in Experimental Heart Failure Circulation, May 1, 2001; 103(17): 2195 - 2200. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. V. Benjafield, C. L. Glenn, X. L. Wang, S. Colagiuri, and B. J. Morris TNFRSF1B in Genetic Predisposition to Clinical Neuropathy and Effect on HDL Cholesterol and Glycosylated Hemoglobin in Type 2 Diabetes Diabetes Care, April 1, 2001; 24(4): 753 - 757. [Abstract] [Full Text]
|
|
|
|
|
|
M. E. YOUNG, S. PATIL, J. YING, C. DEPRE, H. S. AHUJA, G. L. SHIPLEY, S. M. STEPKOWSKI, P. J. A. DAVIES, and H. TAEGTMEYER Uncoupling protein 3 transcription is regulated by peroxisome proliferator-activated receptor {alpha} in the adult rodent heart FASEB J, March 1, 2001; 15(3): 833 - 845. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. B. Atkins, B. Redman, J. Mier, J. Gollob, J. Weber, J. Sosman, B. L MacPherson, and T. Plasse A Phase I Study of CNI-1493, an Inhibitor of Cytokine Release, in Combination with High-Dose Interleukin-2 in Patients with Renal Cancer and Melanoma Clin. Cancer Res., March 1, 2001; 7(3): 486 - 492. [Abstract] [Full Text]
|
|
|
|
|
|
B. Bozkurt, G. Torre-Amione, M. S. Warren, J. Whitmore, O. Z. Soran, A. M. Feldman, and D. L. Mann Results of Targeted Anti-Tumor Necrosis Factor Therapy With Etanercept (ENBREL) in Patients With Advanced Heart Failure Circulation, February 27, 2001; 103(8): 1044 - 1047. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Skudicky, A. Bergemann, K. Sliwa, G. Candy, and P. Sareli Beneficial Effects of Pentoxifylline in Patients With Idiopathic Dilated Cardiomyopathy Treated With Angiotensin-Converting Enzyme Inhibitors and Carvedilol : Results of a Randomized Study Circulation, February 27, 2001; 103(8): 1083 - 1088. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Lefkowitz and J. T. Willerson Prospects for Cardiovascular Research JAMA, February 7, 2001; 285(5): 581 - 587. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Ohtsuka, M. Hamada, G. Hiasa, O. Sasaki, M. Suzuki, Y. Hara, Y. Shigematsu, and K. Hiwada Effect of beta-blockers on circulating levels of inflammatory and anti-inflammatory cytokines in patients with dilated cardiomyopathy J. Am. Coll. Cardiol., February 1, 2001; 37(2): 412 - 417. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Gullestad, H. Aass, J. G. Fjeld, L. Wikeby, A. K. Andreassen, H. Ihlen, S. Simonsen, J. Kjekshus, S. Nitter-Hauge, T. Ueland, et al. Immunomodulating Therapy With Intravenous Immunoglobulin in Patients With Chronic Heart Failure Circulation, January 16, 2001; 103(2): 220 - 225. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Rauchhaus, W. Doehner, D. P. Francis, C. Davos, M. Kemp, C. Liebenthal, J. Niebauer, J. Hooper, H.-D. Volk, A. J. S. Coats, et al. Plasma Cytokine Parameters and Mortality in Patients With Chronic Heart Failure Circulation, December 19, 2000; 102(25): 3060 - 3067. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Schumann, D. Wolf, A. Pahl, K. Brune, T. Papadopoulos, N. van Rooijen, and G. Tiegs Importance of Kupffer Cells for T-Cell-Dependent Liver Injury in Mice Am. J. Pathol., November 1, 2000; 157(5): 1671 - 1683. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P.J. Pugh, K.M. English, T.H. Jones, and K.S. Channer Testosterone: a natural tonic for the failing heart? QJM, October 1, 2000; 93(10): 689 - 694. [Full Text] [PDF]
|
|
|
|
|
|
K. M. Mohler, K. M. Murray, D. L. Mann, and G. Francis Use of Targeted Anticytokine Treatments in Heart Failure Circulation, August 29, 2000; 102 (9): e65 - e65. [Full Text] [PDF]
|
|
|
|
|
|
E. J. Birks, V. J. Owen, P. B. J. Burton, A. E. Bishop, N. R. Banner, A. Khaghani, J. M. Polak, and M. H. Yacoub Tumor Necrosis Factor-{alpha} Is Expressed in Donor Heart and Predicts Right Ventricular Failure After Human Heart Transplantation Circulation, July 18, 2000; 102(3): 326 - 331. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Elliott CARDIOMYOPATHY: Diagnosis and management of dilated cardiomyopathy Heart, July 1, 2000; 84(1): 106 - 106. [Full Text] [PDF]
|
|
|
|
|
|
L. L. Lequier, H. Nikaidoh, S. R. Leonard, J. L. Bokovoy, M. L. White, P. J. Scannon, and B. P. Giroir Preoperative and Postoperative Endotoxemia in Children With Congenital Heart Disease Chest, June 1, 2000; 117(6): 1706 - 1712. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Okuyama, S. Yamaguchi, M. Yamaoka, J. Nitobe, S. Fujii, T. Yoshimura, and H. Tomoike Nitric Oxide Enhances Expression and Shedding of Tumor Necrosis Factor Receptor I (p55) in Endothelial Cells Arterioscler Thromb Vasc Biol, June 1, 2000; 20(6): 1506 - 1511. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kubota, G. S. Bounoutas, M. Miyagishima, T. Kadokami, V. J. Sanders, C. Bruton, P. D. Robbins, C. F. McTiernan, and A. M. Feldman Soluble Tumor Necrosis Factor Receptor Abrogates Myocardial Inflammation but Not Hypertrophy in Cytokine-Induced Cardiomyopathy Circulation, May 30, 2000; 101(21): 2518 - 2525. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P.P. Davey and H. Ashrafian New therapies for heart failure: is thalidomide the answer? QJM, May 1, 2000; 93(5): 305 - 311. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Z. Feuerstein and P. R. Young Apoptosis in cardiac diseases: stress- and mitogen-activated signaling pathways Cardiovasc Res, February 1, 2000; 45(3): 560 - 569. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. N. Sack, R. M. Smith, and L. H. Opie Tumor necrosis factor in myocardial hypertrophy and ischaemia -- an anti-apoptotic perspective Cardiovasc Res, February 1, 2000; 45(3): 688 - 695. [Full Text] [PDF]
|
|
|
|
|
|
J. B. Young Angiotensin-converting enzyme inhibitors and cytokines in heart failure: dose and effect? J. Am. Coll. Cardiol., December 1, 1999; 34(7): 2068 - 2071. [Full Text] [PDF]
|
|
|
|
 |
|
 A New Therapy for CHF Journal Watch (General), July 13, 1999; 1999(713): 3 - 3. [Full Text]
|
|
|
|
 |
|
 Y. Abu-Amer, J. Erdmann, L. Alexopoulou, G. Kollias, F. P. Ross, and S. L. Teitelbaum Tumor Necrosis Factor Receptors Types 1 and 2 Differentially Regulate Osteoclastogenesis J. Biol. Chem., August 25, 2000; 275(35): 27307 - 27310. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Amadou, A. Nawrocki, M. Best-Belpomme, C. Pavoine, and F. Pecker Arachidonic acid mediates dual effect of TNF-alpha on Ca2+ transients and contraction of adult rat cardiomyocytes Am J Physiol Cell Physiol, June 1, 2002; 282(6): C1339 - C1347. [Abstract] [Full Text] [PDF]
|
|