Vasopressin receptor antagonists: From pivotal trials to current practice

Current Heart Failure Reports

Volumn 11, Issue 1, 2014, Pages 10-18

  Kalra, Ankur ^a   Maharaj, Valmiki ^b   Goldsmith, Steven R ^a,b  

^a HENNEPIN COUNTY MEDICAL CENTER   (United States)

^b UNIVERSITY OF MINNESOTA MEDICAL SCHOOL   (United States)

Author keywords

Antidiuretic hormone; Arginine vasopressin; Conivaptan; Tolvaptan

Indexed keywords

ARGIPRESSIN; DOBUTAMINE; LOOP DIURETIC AGENT; NESIRITIDE; NITRATE; VASOPRESSIN RECEPTOR ANTAGONIST;

ACUTE HEART FAILURE; ARTICLE; CARDIAC PATIENT; CARDIOVASCULAR MORTALITY; CLINICAL PRACTICE; DRUG SAFETY; HEART FAILURE; HUMAN; HYPERKALEMIA; OXYGEN THERAPY; POLYURIA; XEROSTOMIA;

ANTIDIURETIC AGENTS; ARGININE VASOPRESSIN; BENZAZEPINES; HEART FAILURE; HORMONE ANTAGONISTS; HUMANS; RECEPTORS, VASOPRESSIN;

EID: 84896734969     PISSN: 15469530     EISSN: 15469549     Source Type: Journal    
DOI: 10.1007/s11897-013-0175-3     Document Type: Article

References (43)

1. Go AS, Mozaffarian D, Roger VL, et al. Heart Disease and Stroke Statistics - 2013 Update: A report from the American Heart Association. Circulation. 2013;127:e6-245.
2. Pang PS, Komajda M, Gheorghiade M. The current and future management of acute heart failure syndromes. Eur Heart J. 2010;31:784-93.
3. Gheorghiade M, Abraham WT, Albert NM, et al. OPTIMIZE-HF Investigators and Coordinators. Systolic blood pressure at admission, clinical characteristics, and outcomes in patients hospitalized with acute heart failure. JAMA. 2006;296:2217-26. (Pubitemid 44708052)
4. Gheorghiade M, Braunwald E. Reconsidering the role for digoxin in the management of acute heart failure syndromes. JAMA. 2009;302(19):2146-7.
5. Bankir L. Antidiuretic action of vasopressin: quantitative aspects and interaction between V1a and V2 receptor-mediated effects. Cardiovasc Res. 2001;51:372-90. (Pubitemid 32718586)
6. Goldsmith SR. Baroreflex control of vasopressin secretion in normal humans. In: Cowley AW, Liard J-F, Ausiello DA, editors. Vasopressin: Cellular and Integrative Functions. New York: Raven Press; 1988. p. 389-97.
7. Goldsmith SR, Gheorghiade M. Vasopressin antagonism in heart failure. J Am Coll Cardiol. 2005;46(10):1785-91. (Pubitemid 41579797)
8. Francis GS, Benedict C, Johnstone DE, et al. Comparison of neuroendocrine activation in patients with left ventricular dysfunction with and without congestive heart failure. A substudy of the Studies of Left Ventricular Dysfunction (SOLVD). Circulation. 1990;82:1724-9. (Pubitemid 20367975)
9. Jard S. Mechanisms of action of vasopressin and vasopressin antagonists. Kidney Int Suppl. 1988;26:S38-42.
10. Xu YJ, Gopalakrishnan V. Vasopressin increases cytosolic free [Ca2+] in the neonatal rat cardiomyocyte. Evidence for V1 subtype receptors. Circ Res. 1991;69:239-45.
11. Nakamura Y, Haneda T, Osaki J, et al. Hypertrophic growth of cultured neonatal rat heart cells mediated by vasopressin V(1A) receptor. Eur J Pharmacol. 2000;391:39-48. (Pubitemid 30138078)
12. Penit J, Faure M, Jard S. Vasopressin and angiotensin II receptors in rat aortic smooth muscle cells in culture. Am J Physiol. 1983;244:E72-82.
13. • Li X, Chan TO, Myers V, et al. Controlled and cardiac-restricted overexpression of the arginine vasopressin V1A receptor causes reversible left ventricular dysfunction through Galphaq-mediated cell signaling. Circulation. 2011;124(5):572-81. In this elegant study, Li et al. demonstrate that over-expression of V1a receptor signaling is capable of producing the dilated cardiomyopathy phenotype in genetically altered mice. Further, the phenotype is 'rescued' by co-expression of an inhibitory gene for G (sub-alpha q) signaling. These experiments unequivocally establish that excessive arginine vasopressin secretion can cause or exacerbate dilated cardiomyopathy and that the mechanism relates to intra-cellular signaling pathways common to other elements of the neurohormonal axis such as angiotensin II. These experiments provide strong support for developing V1a antagonists as a possible therapeutic avenue in patients with heart failure.
14. Nielsen S, Chou CL, Marples D, et al. Vasopressin increases water permeability of kidney collecting duct by inducing translocation of aquaporin-CD water channels to plasma membrane. Proc Natl Acad Sci USA. 1995;92:1013-7.
15. Goldsmith SR, Brandimarte F, Gheorghiade M. Congestion as a therapeutic target in acute heart failure syndromes. Prog Cardiovasc Dis. 2010;52(5):383-92.
16. Felker GM, O'Connor CM, Braunwald E. Heart Failure Clinical Research Network Investigators. Loop diuretics in acute decompensated heart failure: necessary? Evil? A necessary evil? Circ Heart Fail. 2009;2(1):56-62.
17. McCurley JM, Hanlon SU, Wei SK, et al. Furosemide and the progression of left ventricular dysfunction in experimental heart failure. J Am Coll Cardiol. 2004;44(6):1301-7. (Pubitemid 39208889)
18. Costello-Boerrigter LC, Smith WB, Boerrigter G, et al. Vasopressin-2-receptor antagonism augments water excretion without changes in renal hemodynamics or sodium and potassium excretion in human heart failure. Am J Physiol Renal Physiol. 2006;290(2):F273-8. (Pubitemid 43724981)
19. Gheorghiade M, Rossi JS, Cotts W, et al. Characterization and prognostic value of persistent hyponatremia in patients with severe heart failure in the ESCAPE Trial. Arch Intern Med. 2007;167:1998-2005. (Pubitemid 47606641)
20. Gheorghiade M, Abraham WT, Albert NM, et al. Relationship between admission serum sodium concentration and clinical outcomes in patients hospitalized for heart failure: an analysis from the OPTIMIZE-HF registry. Eur Heart J. 2007;28:980-8. (Pubitemid 47343897)
21. Rossi J, Bayram M, Udelson JE, et al. Improvement in hyponatremia during hospitalization for worsening heart failure is associated with improved outcomes: insights from the Acute and Chronic Therapeutic Impact of a Vasopressin Antagonist in Chronic Heart Failure (ACTIV in CHF) trial. Acute Card Care. 2007;9:82-6. (Pubitemid 46955230)
22. Klein L, O'Connor CM, Leimberger JD, et al. Lower serum sodium is associated with increased short-term mortality in hospitalized patients with worsening heart failure: results from the Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure (OPTIME-CHF) study. Circulation. 2005;111:2454-60. (Pubitemid 40696133)
23. Francis GS, Siegel RM, Goldsmith SR, et al. Ann Intern Med. 1985;103(1):1-6.
24. • Goldsmith SR. Hyponatremia and outcomes in patients with heart failure. Heart. 2012;98(24):1761-2. In this editorial, Goldsmith summarizes the available data concerning the relationship between outcomes and hyponatremia in clinical heart failure. The potential mechanisms of the relationship are explored, as are the implications for therapy and the need for additional study.
25. Goldsmith SR. Hyponatremia in heart failure: time for a trial. J Card Fail. 2013;19(6):398-400.
26. Decaux G, Soupart A, Vassart G. Non-peptide arginine vasopressin antagonists: The vaptans. Lancet. 2008;371:1624-32. (Pubitemid 351626846)
27. Shoaf SE, Bramer SL, Bricmont P, Zimmer CA. Pharmacokinetic and Pharmacodynamic Interaction between Tolvaptan, a Non-Peptide AVP Antagonist, and Furosemide or Hydrochlorothiazide. J Cardiovasc Pharmacol. 2007;50(2):213-22. (Pubitemid 47267748)
28. Schrier RW, Gross P, Gheorghiade M, et al. SALT Investigators. Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia. N Engl J Med. 2006;355(20):2099-112. (Pubitemid 44749318)
29. Gheorghiade M, Gattis WA, O'Connor CM, et al. Effects of tolvaptan, a vasopressin antagonist, in patients hospitalized with worsening heart failure: a randomized controlled trial. JAMA. 2004;291:1963-71. (Pubitemid 38544277)
30. Creager MA, Faxon DP, Cutler SS, et al. Contribution of vasopressin to vasoconstriction in patients with congestive heart failure: comparison with the renin-angiotensin system and the sympathetic nervous system. J Am Coll Cardiol. 1986;7:758-65. (Pubitemid 16107118)
31. Goldsmith SR, Francis GS, Cowley Jr. AW, et al. Hemodynamic effects of infused arginine vasopressin in congestive heart failure. J Am Coll Cardiol. 1986;8:779-83. (Pubitemid 16023631)
32. Udelson JE, Smith WB, Hendrix GH, et al. Acute hemodynamic effects of conivaptan, a dual V(1A) and V(2) vasopressin receptor antagonist, in patients with advanced heart failure. Circulation. 2001;104(20):2417-23. (Pubitemid 33108374)
33. Goldsmith SR, Elkayam U, Haught WH, et al. Efficacy and safety of the vasopressin V1A/V2-receptor antagonist conivaptan in acute decompensated heart failure: a dose-ranging pilot study. J Card Fail. 2008;14:641-7.
34. Udelson JE, Orlandi C, Ouyang J, et al. Acute hemodynamic effects of tolvaptan, a vasopressin V2 receptor blocker, in patients with symptomatic heart failure and systolic dysfunction: an international, multicenter, randomized, placebo-controlled trial. J Am Coll Cardiol. 2008;52:1540-5.
35. Udelson JE, McGrew FA, Flores E, et al. Multicenter, randomized, double-blind, placebo-controlled study on the effect of oral tolvaptan on left ventricular dilation and function in patients with heart failure and systolic dysfunction. J Am Coll Cardiol. 2007;49:2151-9. (Pubitemid 46817812)
36. Gheorghiade M, Orlandi C, Burnett JC, et al. Rationale and design of the multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy of vasopressin antagonism in heart failure: outcome study with tolvaptan (EVEREST). J Card Fail. 2005;11:260-9. (Pubitemid 40626781)
37. Gheorghiade M, Konstam MA, Burnett Jr. JC, et al. Short-term clinical effects of tolvaptan, an oral vasopressin antagonist, in patients hospitalized for heart failure: the EVEREST Clinical Status Trials. JAMA. 2007;297:1332-43. (Pubitemid 46513234)
38. Konstam MA, Gheorghiade M, Burnett Jr. JC, et al. Effects of oral tolvaptan in patients hospitalized for worsening heart failure: the EVEREST outcome trial. JAMA. 2007;297:1319-31. (Pubitemid 46513233)
39. • Lanfear DE, Sabbah HN, Goldsmith SR, et al. EVEREST trial investigators. Association of arginine vasopressin levels with outcomes and the effect of V2 blockade in patients hospitalized for heart failure with reduced ejection fraction: insights from the EVEREST trial. Circ Heart Fail. 2013;6(1):47-52. In this retrospective analysis of data from the EVEREST trial, Lanfear et al. report on the relationship between increased vasopressin levels and outcomes, as well as response to therapy in patients treated with either placebo or tolvaptan. The data show, for the first time in a large series of patients with clinical heart failure on appropriate background therapy, that elevated plasma AVP levels are associated with worse outcomes. However, while AVP levels were higher in patients treated with tolvaptan, the outcomes were not worse in this group.
40. Matsue Y, Suzuki M, Seya M, et al. Tolvaptan reduces the risk of worsening renal function in patients with acute decompensated heart failure in high-risk population. J Cardiol. 2013;61(2):169-74.
41. • Hauptman PJ, Burnett J, Gheorghiade M, et al. Everest Investigators. Clinical course of patients with hyponatremia and decompensated systolic heart failure and the effect of vasopressin receptor antagonism with tolvaptan. J Card Fail. 2013;19(6):390-7. In this retrospective analysis of the EVEREST trial, Hauptman et al. describe the clinical course of hyponatremic patients and their response to tolvaptan therapy vs. placebo as compared to normonatremic patients. Although the relevance of the information is limited by relatively few patients and a small number of events, the analysis suggests that hyponatremic patients in general have worse outcomes, may have a somewhat better clinical response regarding dyspnea when treated with tolvaptan, and, in the cohort with serum sodium below 13 0meq/liter, better cardiovascular outcomes when treated with tolvaptan. This analysis provides support for the usefulness of performing a prospective, randomized, controlled trial of tolvaptan therapy in hyponatremic heart failure patients.
42. Udelson JE, Bilsker M, Hauptman PJ, et al. A multicenter, randomized, double-blind, placebo-controlled study of tolvaptan monotherapy compared to furosemide and the combination of tolvaptan and furosemide in patients with heart failure and systolic dysfunction. J Card Fail. 2011;17(12):973-81.
43. Goldsmith SR, Gilbertson DT, Mackedanz SA, Swan SK. Renal effects of conivaptan, furosemide, and the combination in patients with chronic heart failure. J Card Fail. 2011;17(12):982-9.