Log in | Register

Dobutamine for patients with severe heart failure: a systematic review and meta-analysis of randomised controlled trials

Catherine L. Tacon| John McCaffrey| Anthony Delaney
Systematic Review
Volume 38, Issue 3 / March , 2012

Pages 359 - 367

Abstract

Purpose

Dobutamine is recommended for patients with severe heart failure; however uncertainty exists as to its effect on mortality. This study aims to critically review the literature to evaluate whether dobutamine, compared with placebo or standard care, is associated with lower mortality and a range of secondary outcomes, in patients with severe heart failure.

Methods

A systematic review and meta-analysis of randomised controlled trials was performed. PubMed, EMBASE, the Cochrane Central Trials Registry, the metaRegister of Controlled Trials and bibliographies of retrieved articles were searched. Randomised trials comparing dobutamine with placebo or standard care, in human, adult patients with severe heart failure, were included if they reported at least one outcome of interest. Data regarding trial validity, methodological processes and clinical outcomes were extracted, and a meta-analysis was performed.

Results

Fourteen studies, with 673 participants, met the inclusion criteria and were included; 13 studies reported mortality. There was minimal heterogeneity (I2 = 4.5%). The estimate of the odds ratio for mortality for patients with severe heart failure treated with dobutamine compared with standard care or placebo was 1.47 (95% confidence interval 0.98–2.21, p = 0.06).

Conclusions

This meta-analysis showed that dobutamine is not associated with improved mortality in patients with heart failure, and there is a suggestion of increased mortality associated with its use, although this did not reach the conventional level of statistical significance. Further research to define the role of dobutamine in treatment of severe heart failure should be a priority.

Keywords

References

  1. Dickstein K, Cohen-Solal A, Filippatos G, McMurray JJ, Ponikowski P, Poole-Wilson PA, Stromberg A, van Veldhuisen DJ, Atar D, Hoes AW, Keren A, Mebazaa A, Nieminen M, Priori SG, Swedberg K, Vahanian A, Camm J, De Caterina R, Dean V, Funck-Brentano C, Hellemans I, Kristensen SD, McGregor K, Sechtem U, Silber S, Tendera M, Widimsky P, Zamorano JL (2008) ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the task force for the diagnosis and treatment of acute and chronic heart failure 2008 of the European Society Of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur Heart J 29:2388–2442. doi:10.1093/eurheartj/ehn309
    • View reference on PubMed
  2. Weintraub NL, Collins SP, Pang PS, Levy PD, Anderson AS, Arslanian-Engoren C, Gibler WB, McCord JK, Parshall MB, Francis GS, Gheorghiade M (2010) Acute heart failure syndromes: emergency department presentation, treatment, and disposition: current approaches and future aims: a scientific statement from the American Heart Association. Circulation 122:1975–1996. doi:10.1161/CIR.0b013e3181f9a223
    • View reference on PubMed
  3. Follath F, Yilmaz MB, Delgado JF, Parissis JT, Porcher R, Gayat E, Burrows N, McLean A, Vilas-Boas F, Mebazaa A (2011) Clinical presentation, management and outcomes in the acute heart failure global survey of standard treatment (ALARM-HF). Intensive Care Med. doi:10.1007/s00134-010-2113-0
  4. CONSENSUS (1987) Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). The CONSENSUS Trial Study Group. N Engl J Med 316:1429–1435. doi:10.1056/NEJM198706043162301
  5. SOLVD (1991) Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. The SOLVD Investigators. N Engl J Med 325:293–302. doi:10.1056/NEJM199108013250501
  6. Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, Palensky J, Wittes J (1999) The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med 341:709–717. doi:10.1056/NEJM199909023411001
    • View reference on PubMed
  7. Zannad F, McMurray JJ, Krum H, van Veldhuisen DJ, Swedberg K, Shi H, Vincent J, Pocock SJ, Pitt B (2011) Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med 364:11–21. doi:10.1056/NEJMoa1009492
    • View reference on PubMed
  8. Rivero-Ayerza M, Theuns DA, Garcia–Garcia HM, Boersma E, Simoons M, Jordaens LJ (2006) Effects of cardiac resynchronization therapy on overall mortality and mode of death: a meta-analysis of randomized controlled trials. Eur Heart J 27:2682–2688. doi:10.1093/eurheartj/ehl203
    • View reference on PubMed
  9. II CIBIS- (1999) The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet 353:9–13. doi:S0140673698111819
  10. Lechat P, Packer M, Chalon S, Cucherat M, Arab T, Boissel JP (1998) Clinical effects of beta-adrenergic blockade in chronic heart failure: a meta-analysis of double-blind, placebo-controlled, randomized trials. Circulation 98:1184–1191
    • View reference on PubMed
  11. HF MERIT- (1999) Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in congestive heart failure (MERIT-HF). Lancet 353:2001–2007. doi:S0140673699044402
  12. Packer M, Coats AJ, Fowler MB, Katus HA, Krum H, Mohacsi P, Rouleau JL, Tendera M, Castaigne A, Roecker EB, Schultz MK, DeMets DL (2001) Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med 344:1651–1658. doi:10.1056/NEJM200105313442201
    • View reference on PubMed
  13. Packer M, Fowler MB, Roecker EB, Coats AJ, Katus HA, Krum H, Mohacsi P, Rouleau JL, Tendera M, Staiger C, Holcslaw TL, Amann-Zalan I, DeMets DL (2002) Effect of carvedilol on the morbidity of patients with severe chronic heart failure: results of the carvedilol prospective randomized cumulative survival (COPERNICUS) study. Circulation 106:2194–2199
    • View reference on PubMed
  14. Masip J, Roque M, Sanchez B, Fernandez R, Subirana M, Exposito JA (2005) Noninvasive ventilation in acute cardiogenic pulmonary edema: systematic review and meta-analysis. JAMA 294:3124–3130. doi:10.1001/jama.294.24.3124
    • View reference on PubMed
  15. Triposkiadis F, Parissis JT, Starling RC, Skoularigis J, Louridas G (2009) Current drugs and medical treatment algorithms in the management of acute decompensated heart failure. Expert Opin Investig Drugs 18:695–707. doi:10.1517/13543780902922660
    • View reference on PubMed
  16. Parissis JT, Rafouli-Stergiou P, Stasinos V, Psarogiannakopoulos P, Mebazaa A (2010) Inotropes in cardiac patients: update 2011. Curr Opin Crit Care 16:432–441. doi:10.1097/MCC.0b013e32833e10fb
    • View reference on PubMed
  17. Haynes RB, McKibbon KA, Wilczynski NL, Walter SD, Werre SR (2005) Optimal search strategies for retrieving scientifically strong studies of treatment from medline: analytical survey. BMJ 330:1179
    • View reference on PubMed
  18. Wong SS, Wilczynski NL, Haynes RB (2006) Developing optimal search strategies for detecting clinically sound treatment studies in EMBASE. J Med Libr Assoc 94:41–47
    • View reference on PubMed
  19. Juni P, Altman DG, Egger M (2001) Systematic reviews in health care: assessing the quality of controlled clinical trials. BMJ 323:42–46
    • View reference on PubMed
  20. Schulz KF, Chalmers I, Hayes RJ, Altman DG (1995) Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA 273:408–412
  21. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634
    • View reference on PubMed
  22. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560
    • View reference on PubMed
  23. Villar J, Mackey ME, Carroli G, Donner A (2001) Meta-analyses in systematic reviews of randomized controlled trials in perinatal medicine: comparison of fixed and random effects models. Stat Med 20:3635–3647
    • View reference on PubMed
  24. Deeks JJ (2002) Issues in the selection of a summary statistic for meta-analysis of clinical trials with binary outcomes. Stat Med 21:1575–1600
    • View reference on PubMed
  25. Adamopoulos S, Parissis JT, Iliodromitis EK, Paraskevaidis I, Tsiapras D, Farmakis D, Karatzas D, Gheorghiade M, Filippatos GS, Kremastinos DT (2006) Effects of levosimendan versus dobutamine on inflammatory and apoptotic pathways in acutely decompensated chronic heart failure. Am J Cardiol 98:102–106
    • View reference on PubMed
  26. Adamopoulos S, Piepoli M, Qiang F, Pissimissis E, Davies M, Bernardi L, Forfar C, Sleight P, Coats A (1995) Effects of pulsed beta-stimulant therapy on beta-adrenoceptors and chronotropic responsiveness in chronic heart failure. Lancet 345:344–349
    • View reference on PubMed
  27. Bader FM, Gilbert EM, Mehta NA, Bristow MR (2010) Double-blind placebo-controlled comparison of enoximone and dobutamine infusions in patients with moderate to severe chronic heart failure. Congest Heart Fail 16:265–270. doi:10.1111/j.1751-7133.2010.00185.x
    • View reference on PubMed
  28. Cleland JG, Ghosh J, Freemantle N, Kaye GC, Nasir M, Clark AL, Coletta AP (2004) Clinical trials update and cumulative meta-analyses from the American College of Cardiology: WATCH, SCD-HeFT, DINAMIT, CASINO, INSPIRE, STRATUS-US, RIO-Lipids and cardiac resynchronisation therapy in heart failure. Eur J Heart Fail 6:501–508
    • View reference on PubMed
  29. Dies F, Krell MJ, Whitlow P, Liang C-S, Goldenberg I, Applefield MM, Gilbert EM (1986) Intermittent dobutamine in ambulatory outpatients with chronic heart failure. Circulation 74:II–38
  30. Elis A, Bental T, Kimchi O, Ravid M, Lishner M (1998) Intermittent dobutamine treatment in patients with chronic refractory congestive heart failure: a randomized, double-blind, placebo-controlled study. Clin Pharmacol Ther 63:682–685
    • View reference on PubMed
  31. Erlemeier HH, Kupper W, Bleifeld W (1992) Intermittent infusion of dobutamine in the therapy of severe congestive heart failure—long-term effects and lack of tolerance. Cardiovasc Drugs Ther 6:391–398
    • View reference on PubMed
  32. Leier CV, Huss P, Lewis RP, Unverferth DV (1982) Drug-induced conditioning in congestive heart failure. Circulation 65:1382–1387
    • View reference on PubMed
  33. Liang CS, Sherman LG, Doherty JU, Wellington K, Lee VW, Hood WB (1984) Sustained improvement of cardiac function in patients with congestive heart failure after short-term infusion of dobutamine. Circulation 69:113–119
    • View reference on PubMed
  34. Nanas JN, Tsagalou EP, Kanakakis J, Nanas SN, Terrovitis JV, Moon T, Anastasiou-Nana MI (2004) Long-term intermittent dobutamine infusion, combined with oral amiodarone for end-stage heart failure: a randomized double-blind study. Chest 125:1198–1204
    • View reference on PubMed
  35. Nieminen MS, Akkila J, Hasenfuss G, Kleber FX, Lehtonen LA, Mitrovic V, Nyquist O, Remme WJ (2000) Hemodynamic and neurohumoral effects of continuous infusion of levosimendan in patients with congestive heart failure. J Am Coll Cardiol 36:1903–1912
    • View reference on PubMed
  36. Oliva F, Latini R, Politi A, Staszewsky L, Maggioni AP, Nicolis E, Mauri F (1999) Intermittent 6-month low-dose dobutamine infusion in severe heart failure: DICE multicenter trial. Am Heart J 138:247–253
    • View reference on PubMed
  37. Sindone AP, MacDonald PS, Keogh AM (1998) Haemodynamic, neurohumoral and symptomatic effects of dobutamine, dopamine and milrinone in severe heart failure. [abstract]. Aust N Z J Med 28:113
  38. Wimmer A, Stanek B, Kubecova L, Vitovec J, Spinar J, Yilmaz N, Kos T, Hartter E, Frey B, Pacher R (1999) Effects of prostaglandin E1, dobutamine and placebo on hemodynamic, renal and neurohumoral variables in patients with advanced heart failure. Jpn Heart J 40:321–334
    • View reference on PubMed
  39. Grose R, Strain J, Greenberg M, LeJemtel TH (1986) Systemic and coronary effects of intravenous milrinone and dobutamine in congestive heart failure. J Am Coll Cardiol 7:1107–1113
    • View reference on PubMed
  40. Petersen JW, Felker GM (2008) Inotropes in the management of acute heart failure. Crit Care Med 36:S106–S111. doi:10.1097/01.CCM.0000296273.72952.39
    • View reference on PubMed
  41. Echt DS, Liebson PR, Mitchell LB, Peters RW, Obias-Manno D, Barker AH, Arensberg D, Baker A, Friedman L, Greene HL et al (1991) Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial. N Engl J Med 324:781–788
    • View reference on PubMed
  42. Dar O, Cowie MR (2008) Acute heart failure in the intensive care unit: epidemiology. Crit Care Med 36:S3–S8. doi:10.1097/01.CCM.0000296264.41365.80
    • View reference on PubMed
  43. Lehtonen LA, Antila S, Pentikainen PJ (2004) Pharmacokinetics and pharmacodynamics of intravenous inotropic agents. Clin Pharmacokinet 43:187–203
    • View reference on PubMed
  44. Chalmers I (1990) Underreporting research is scientific misconduct. JAMA 263:1405–1408
    • View reference on PubMed
  45. Shields PG (2000) Publication bias is a scientific problem with adverse ethical outcomes: the case for a section for null results. Cancer Epidemiol Biomarkers Prev 9:771–772
    • View reference on PubMed
  46. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol 62:e1–e34. doi:10.1016/j.jclinepi.2009.06.006
    • View reference on PubMed
  47. Abraham WT, Adams KF, Fonarow GC, Costanzo MR, Berkowitz RL, LeJemtel TH, Cheng ML, Wynne J (2005) In-hospital mortality in patients with acute decompensated heart failure requiring intravenous vasoactive medications: an analysis from the Acute Decompensated Heart Failure National Registry (ADHERE). J Am Coll Cardiol 46:57–64. doi:10.1016/j.jacc.2005.03.051
    • View reference on PubMed
  48. Mebazaa A, Parissis J, Porcher R, Gayat E, Nikolaou M, Boas FV, Delgado JF, Follath F (2011) Short-term survival by treatment among patients hospitalized with acute heart failure: the global ALARM-HF registry using propensity scoring methods. Intensive Care Med 37:290–301. doi:10.1007/s00134-010-2073-4
    • View reference on PubMed
  49. Felker GM, Benza RL, Chandler AB, Leimberger JD, Cuffe MS, Califf RM, Gheorghiade M, O’Connor CM (2003) Heart failure etiology and response to milrinone in decompensated heart failure: results from the OPTIME-CHF study. J Am Coll Cardiol 41:997–1003
    • View reference on PubMed
  50. Mebazaa A, Nieminen MS, Packer M, Cohen-Solal A, Kleber FX, Pocock SJ, Thakkar R, Padley RJ, Poder P, Kivikko M (2007) Levosimendan vs dobutamine for patients with acute decompensated heart failure: the SURVIVE Randomized Trial. JAMA 297:1883–1891
    • View reference on PubMed
  51. Delaney A, Bradford C, McCaffrey J, Bagshaw SM, Lee R (2010) Levosimendan for the treatment of acute severe heart failure: A meta-analysis of randomised controlled trials. Int J Cardiol 138:281–289. doi:10.1016/j.ijcard.2008.08.020
    • View reference on PubMed
  52. Jessup M, Abraham WT, Casey DE, Feldman AM, Francis GS, Ganiats TG, Konstam MA, Mancini DM, Rahko PS, Silver MA, Stevenson LW, Yancy CW (2009) 2009 focused update: ACCF/AHA guidelines for the diagnosis and management of heart failure in adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation 119:1977–2016. doi:10.1161/CIRCULATIONAHA.109.192064
    • View reference on PubMed

Sign In

Connect with ICM

Top 5 Articles Editors Picks Supplement