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Novel pharmacologic therapy of heart failure

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Current Treatment Options in Cardiovascular Medicine Aims and scope Submit manuscript

Opinion statement

The prevalence of congestive heart failure is progressively increasing and despite recent advances in therapeutics, there is a continuing need for novel effective therapies. New, investigational treatment strategies include inotropic drugs, neurohormonal antagonists, anticytokine and anti-inflammatory strategies, hormonal therapies, and nutritional supplements. Current positive inotropes (eg, dobutamine and phosphodiesterase inhibitors) provide symptomatic relief, but newer agents may have a better adverse effect profile. Angiotensin-converting enzyme (ACE) inhibitors should remain first-line treatment with angiotensin receptor blockers used in ACE inhibitor-intolerant patients. Many new neurohormonal antagonists have recently been investigated and eplerenone has demonstrated clinical benefit. New hormonal, anticytokine, and anti-inflammatory therapies have shown benefit in small trials, but results in larger trials have been disappointing. Other approaches are currently being tested in large trials that will clarify their role. Nutritional supplements need to be tested in a large prospective trial before they can be recommended.

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References and Recommended Reading

  1. Hunt SA, Baker DW, Chin MH, et al.: ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: executive summary. A report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines (Committee to revise the 1995 Guidelines for the Evaluation and Management of Heart Failure). J Am Coll Cardiol 2001, 38:2101–2113. This consensus document from the AHA and ACC provides current guidelines in the current evaluation, management, and treatment of CHF.

    Article  PubMed  CAS  Google Scholar 

  2. McMurray J, Pfeffer MA: New therapeutic options in congestive heart failure: parts I and II. Circulation 2002, 105:2099–2106; 2223–2098. A comprehensive review of new therapies, including nonpharmacologic approaches.

    Article  PubMed  Google Scholar 

  3. Follath F, Cleland JG, Just H, et al.: Efficacy and safety of intravenous levosimendan compared with dobutamine in severe low-output heart failure (the LIDO study): a randomised double-blind trial. Lancet 2002, 360:196–202. The first study with a new agent for acute decompensated heart failure to suggest an improvement in long-term outcomes. Levosimendan increased cardiac index, decreased pulmonary pressures, caused fewer adverse effects, and improved 180-day mortality compared with dobutamine.

    Article  PubMed  CAS  Google Scholar 

  4. Uretsky BF, Jessup M, Konstam MA, et al.: Multicenter trial of oral enoximone in patients with moderate to moderately severe congestive heart failure. Lack of benefit compared with placebo. Enoximone Multicenter Trial Group. Circulation 1990, 82:774–780.

    PubMed  CAS  Google Scholar 

  5. Lee HR, Hershberger RE, Port JD, et al.: Low-dose enoximone in subjects awaiting cardiac transplantation. Clinical results and effects on beta-adrenergic receptors. J Thorac Cardiovasc Surg 1991, 102:246–258.

    PubMed  CAS  Google Scholar 

  6. O’Connell JB, Gilbert EM, Renlund DG, et al.: Enoximone as a bridge to heart transplantation: the Utah experience. J Heart Lung Transplant 1991, 10:477–481.

    PubMed  CAS  Google Scholar 

  7. Shakar SF, Abraham WT, Gilbert EM, et al.: Combined oral positive inotropic and beta-blocker therapy for treatment of refractory class IV heart failure. J Am Coll Cardiol 1998, 31:1336–1340.

    Article  PubMed  CAS  Google Scholar 

  8. Swedberg K, Bristow MR, Cohn JN, et al.: Effects of sustained-release moxonidine, an imidazoline agonist, on plasma norepinephrine in patients with chronic heart failure. Circulation 2002, 105:1797–1803.

    Article  PubMed  CAS  Google Scholar 

  9. Jones CG, Cleland JG: Meeting report—the LIDO, HOPE, MOXCON and WASH studies. Heart Outcomes Prevention Evaluation. The Warfarin/Aspirin Study of Heart Failure. Eur J Heart Fail 1999, 1:425–431.

    Article  PubMed  Google Scholar 

  10. Teerlink JR: Reversal of left ventricular remodeling: role of the endothelin pathway. J Card Fail 2002, 8:S494-S499.

    Article  PubMed  CAS  Google Scholar 

  11. Teerlink JR: Recent heart failure trials of neurohormonal modulation (OVERTURE and ENABLE): approaching the asymptote of efficacy? J Card Fail 2002, 8:124–127.

    Article  PubMed  Google Scholar 

  12. Louis A, Cleland JG, Crabbe S, et al.: Clinical trials update: CAPRICORN, COPERNICUS, MIRACLE, STAF, RITZ-2, RECOVER and RENAISSANCE and cachexia and cholesterol in heart failure. Highlights of the Scientific Sessions of the American College of Cardiology, 2001. Eur J Heart Fail 2001, 3:381–387.

    Article  PubMed  CAS  Google Scholar 

  13. Coletta AP, Cleland JG: Clinical trials update: highlights of the scientific sessions of the XXIII Congress of the European Society of Cardiology—WARIS II, ESCAMI, PAFAC, RITZ-1 and TIME. Eur J Heart Fail 2001, 3:747–750.

    Article  PubMed  CAS  Google Scholar 

  14. Douglas SA, Tayara L, Ohlstein EH, et al.: Congestive heart failure and expression of myocardial urotensin II. Lancet 2002, 359:1990–1997.

    Article  PubMed  CAS  Google Scholar 

  15. Pitt B, Zannad F, Remme WJ, et al.: The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med 1999, 341:709–717.

    Article  PubMed  CAS  Google Scholar 

  16. Pitt B, Remme W, Zannad F, et al.: Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003, 348:1309–1321. This large recent trial extends the concept of aldosterone antagonism to postmyocardial infarction patients with heart failure.

    Article  PubMed  CAS  Google Scholar 

  17. Pitt B, Segal R, Martinez FA, et al.: Randomised trial of losartan versus captopril in patients over 65 with heart failure (Evaluation of Losartan in the Elderly Study, ELITE). Lancet 1997, 349:747–752.

    Article  PubMed  CAS  Google Scholar 

  18. Pitt B, Poole-Wilson PA, Segal R, et al.: Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomised trial—the Losartan Heart Failure Survival Study ELITE II. Lancet 2000, 355:1582–1587.

    Article  PubMed  CAS  Google Scholar 

  19. Dickstein K, Kjekshus J: Effects of losartan and captopril on mortality and morbidity in high-risk patients after acute myocardial infarction: the OPTIMAAL randomised trial. Optimal Trial in Myocardial Infarction with Angiotensin II Antagonist Losartan. Lancet 2002, 360:752–760.

    Article  PubMed  CAS  Google Scholar 

  20. McKelvie RS, Yusuf S, Pericak D, et al.: Comparison of candesartan, enalapril, and their combination in congestive heart failure: randomized evaluation of strategies for left ventricular dysfunction (RESOLVD) pilot study. The RESOLVD Pilot Study Investigators. Circulation 1999, 100:1056–1064.

    PubMed  CAS  Google Scholar 

  21. Cohn JN, Tognoni G: A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med 2001, 345:1667–1675. This well-designed trial demonstrated a beneficial effect of valsartan on mortality in patients not receiving ACE inhibitors and supported FDA approval of valsartan for ACE-intolerant heart failure patients. The investigators also did a superb job of obtaining information regarding neurohormonal activation and ventricular remodeling; thus, there will be additional data forthcoming regarding changes in the disease process from this study.

    Article  PubMed  CAS  Google Scholar 

  22. Rouleau JL, Pfeffer MA, Stewart DJ, et al.: Comparison of vasopeptidase inhibitor, omapatrilat, and lisinopril on exercise tolerance and morbidity in patients with heart failure: IMPRESS randomised trial. Lancet 2000, 356:615–620.

    Article  PubMed  CAS  Google Scholar 

  23. Packer M, Califf RM, Konstam MA, et al.: Comparison of omapatrilat and enalapril in patients with chronic heart failure: the Omapatrilat Versus Enalapril Randomized Trial of Utility in Reducing Events (OVERTURE). Circulation 2002, 106:920–926.

    Article  PubMed  CAS  Google Scholar 

  24. Young J, Abraham WT, Stevenson LW: Intravenous nesiritide vs nitroglycerin for treatment of decompensated congestive heart failure. JAMA 2002, 287:1531–1540. This trial demonstrated that compared with nitroglycerin, nesiritide caused a dose-dependent reduction in PCWP and systolic arterial pressure and may improve symptoms in acutely decompensated heart failure patients with dyspnea at rest or minimal activity. The results of this trial supported the FDA approval of nesiritide for the treatment of these patients.

    Article  CAS  Google Scholar 

  25. Mann DL: Inflammatory mediators and the failing heart: past, present, and the foreseeable future. Circ Res 2002, 91:988–998. The leader in the field reviews the pathophysiology of inflammatory mediators, recent trials addressing this mechanism, and future directions.

    Article  PubMed  CAS  Google Scholar 

  26. Krum H: Tumor necrosis factor-alpha blockade as a therapeutic strategy in heart failure (RENEWAL and ATTACH): unsuccessful, to be specific. J Card Fail 2002, 8:365–368.

    Article  PubMed  Google Scholar 

  27. Skudicky D, Bergemann A, Sliwa K, et al.: Beneficial effects of pentoxifylline in patients with idiopathic dilated cardiomyopathy treated with angiotensinconverting enzyme inhibitors and carvedilol: results of a randomized study. Circulation 2001, 103:1083–1088.

    PubMed  CAS  Google Scholar 

  28. Torre-Amione G, Young JB, Sestier F, et al.: Immune modulation therapy reduces deaths and hospitalization in class III/IV chronic heart failure patients: results of a randomized clinical trial. J Card Fail 2002, 8:S10.

    Google Scholar 

  29. Gullestad L, Aass H, Fjeld JG, et al.: Immunomodulating therapy with intravenous immunoglobulin in patients with chronic heart failure. Circulation 2001, 103:220–225.

    PubMed  CAS  Google Scholar 

  30. Fazio S, Sabatini D, Capaldo B, et al.: A preliminary study of growth hormone in the treatment of dilated cardiomyopathy. N Engl J Med 1996, 334:809–814.

    Article  PubMed  CAS  Google Scholar 

  31. Nagaya N, Uematsu M, Kojima M, et al.: Elevated circulating level of ghrelin in cachexia associated with chronic heart failure: relationships between ghrelin and anabolic/catabolic factors. Circulation 2001, 104:2034–2038.

    PubMed  CAS  Google Scholar 

  32. Morkin E, Pennock GD, Spooner PH, et al.: Clinical and experimental studies on the use of 3,5-diiodothyropropionic acid, a thyroid hormone analogue, in heart failure. Thyroid 2002, 12:527–533.

    Article  PubMed  CAS  Google Scholar 

  33. Chaitman B, Skettino S, DeQuattro V: Improved exercise performance on ranolazine in patients with chronic angina and a history of heart failure: the MARISA trial [abstract]. J Am Coll Cardiol 2001:149A.

  34. Cosin J, Diez J: Torasemide in chronic heart failure: results of the TORIC study. Eur J Heart Fail 2002, 4:507–513.

    Article  PubMed  CAS  Google Scholar 

  35. Gottlieb SS, Brater DC, Thomas I, et al.: BG9719 (CVT-124), an A1 adenosine receptor antagonist, protects against the decline in renal function observed with diuretic therapy. Circulation 2002, 105:1348–1353.

    Article  PubMed  CAS  Google Scholar 

  36. Tauchert M: Efficacy and safety of crataegus extract WS 1442 in comparison with placebo in patients with chronic stable New York Heart Association class-III heart failure. Am Heart J 2002, 143:910–915.

    Article  PubMed  CAS  Google Scholar 

  37. Yaoita H, Ogawa K, Maehara K, et al.: Attenuation of ischemia/reperfusion injury in rats by a caspase inhibitor. Circulation 1998, 97:276–281.

    PubMed  CAS  Google Scholar 

  38. Struthers AD, Donnan PT, Lindsay P, et al.: Effect of allopurinol on mortality and hospitalisations in chronic heart failure: a retrospective cohort study. Heart 2002, 87:229–234.

    Article  PubMed  CAS  Google Scholar 

  39. Baggio E, Gandini R, Plancher AC, et al.: Italian multicenter study on the safety and efficacy of coenzyme Q10 as adjunctive therapy in heart failure. CoQ10 Drug Surveillance Investigators. Mol Aspects Med 1994, 15:S287-S294.

    Article  PubMed  Google Scholar 

  40. Khatta M, Alexander BS, Krichten CM, et al.: The effect of coenzyme Q10 in patients with congestive heart failure. Ann Intern Med 2000, 132:636–640.

    PubMed  CAS  Google Scholar 

  41. Seligmann H, Halkin H, Rauchfleisch S, et al.: Thiamine deficiency in patients with congestive heart failure receiving long-term furosemide therapy: a pilot study. Am J Med 1991, 91:151–155.

    Article  PubMed  CAS  Google Scholar 

  42. Shimon I, Almog S, Vered Z, et al.: Improved left ventricular function after thiamine supplementation in patients with congestive heart failure receiving longterm furosemide therapy. Am J Med 1995, 98:485–490.

    Article  PubMed  CAS  Google Scholar 

  43. Gordon A, Hultman E, Kaijser L, et al.: Creatine supplementation in chronic heart failure increases skeletal muscle creatine phosphate and muscle performance. Cardiovasc Res 1995, 30:413–418.

    Article  PubMed  CAS  Google Scholar 

  44. Azuma J, Sawamura A, Awata N: Usefulness of taurine in chronic congestive heart failure and its prospective application. Jpn Circ J 1992, 56:95–99.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Cardiology, San Francisco Veterans Affairs Medical Center, 111C, 4150 Clement Street, 94121-1545, San Francisco, CA, USA

    Steven J. Hussein MD & John R. Teerlink MD

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  1. Steven J. Hussein MD
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Hussein, S.J., Teerlink, J.R. Novel pharmacologic therapy of heart failure. Curr Treat Options Cardio Med 5, 321–335 (2003). https://doi.org/10.1007/s11936-003-0031-y

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  • DOI: https://doi.org/10.1007/s11936-003-0031-y

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