Short-term add-on therapy with angiotensin receptor blocker for end-stage inotrope-dependent heart failure patients: B-type natriuretic peptide reduction in a randomized clinical trial

Marcelo E Ochiai, Euler C O Brancalhão, Raphael S N Puig, Kelly R N Vieira, Juliano N Cardoso, Múcio Tavares de Oliveira Jr, Antonio C P Barretto, Marcelo E Ochiai, Euler C O Brancalhão, Raphael S N Puig, Kelly R N Vieira, Juliano N Cardoso, Múcio Tavares de Oliveira Jr, Antonio C P Barretto

Abstract

Objective: We aimed to evaluate angiotensin receptor blocker add-on therapy in patients with low cardiac output during decompensated heart failure.

Methods: We selected patients with decompensated heart failure, low cardiac output, dobutamine dependence, and an ejection fraction <0.45 who were receiving an angiotensin-converting enzyme inhibitor. The patients were randomized to losartan or placebo and underwent invasive hemodynamic and B-type natriuretic peptide measurements at baseline and on the seventh day after intervention. ClinicalTrials.gov: NCT01857999.

Results: We studied 10 patients in the losartan group and 11 patients in the placebo group. The patient characteristics were as follows: age 52.7 years, ejection fraction 21.3%, dobutamine infusion 8.5 mcg/kg.min, indexed systemic vascular resistance 1918.0 dynes.sec/cm(5).m(2), cardiac index 2.8 L/min.m(2), and B-type natriuretic peptide 1,403 pg/mL. After 7 days of intervention, there was a 37.4% reduction in the B-type natriuretic peptide levels in the losartan group compared with an 11.9% increase in the placebo group (mean difference, -49.1%; 95% confidence interval: -88.1 to -9.8%, p = 0.018). No significant difference was observed in the hemodynamic measurements.

Conclusion: Short-term add-on therapy with losartan reduced B-type natriuretic peptide levels in patients hospitalized for decompensated severe heart failure and low cardiac output with inotrope dependence.

Conflict of interest statement

No potential conflict of interest was reported.

Figures

Figure 1
Figure 1
BNP evolution according to losartan or placebo group.
Figure 2
Figure 2
Survival curves according to losartan or placebo.

References

    1. Jessup M, Abraham WT, Casey DE, Feldman AM, Francis GS, Ganiats TG, et al. 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. 2009;119(14):1977–2016.
    1. McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Bohm M, Dickstein K, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012. Eur J Heart Fail. 2012;14(8):803–69. The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC.
    1. Ochiai ME, Cardoso JN, Vieira KR, Lima MV, Brancalhao EC, Barretto AC. Predictors of low cardiac output in decompensated severe heart failure. Clinics. 2011;66(2):239–44.
    1. Johnson W, Omland T, Hall C, Lucas C, Myking OL, Collins C, et al. Neurohormonal activation rapidly decreases after intravenous therapy with diuretics and vasodilators for class IV heart failure. J Am Coll Cardiol. 2002;39(10):1623–9.
    1. Mullens W, Abrahams Z, Francis GS, Sokos G, Starling RC, Young JB, et al. Usefulness of isosorbide dinitrate and hydralazine as add-on therapy in patients discharged for advanced decompensated heart failure. Am J Cardiol. 2009;103(8):1113–9.
    1. Felker GM, Pang PS, Adams KF, Cleland JG, Cotter G, Dickstein K, et al. Clinical trials of pharmacological therapies in acute heart failure syndromes: lessons learned and directions forward. Circ Heart Fail. 2010;3(2):314–25.
    1. Gheorghiade M, De Luca L, Fonarow GC, Filippatos G, Metra M, Francis GS. Pathophysiologic targets in the early phase of acute heart failure syndromes. Am J Cardiol. 2005;96(6A):11G–17G.
    1. McMurray JJ, Östergren J, Swedberg K, Granger CB, Held P, Michelson EL, et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial. Lancet. 2003;362(9386):767–71.
    1. Cohn JN, Tognoni G. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med. 2001;345(23):1667–75. for the Valsartan Heart Failure Trial Investigators.
    1. Cardoso J, Novaes M, Ochiai M, Regina K, Morgado P, Munhoz R, et al. Chagas cardiomyopathy: prognosis in clinical and hemodynamic profile C. Arq Bras Cardiol. 2010;95(4):518–23.
    1. Ochiai ME, Barretto AC, Cardoso JN, Munhoz RT, Morgado PC, Ramires JA. Angiotensin II receptor blocker add-on therapy for low cardiac output in decompensated heart failure. Arq Bras Cardiol. 2010;94(2):219–22.
    1. Voyce SJ, Urbach D, Rippe JM. Intensive Care Medicine. In: Rippe J M, Irwin R S, Alpert J S, Fink M P, editors. Little. (eds) 2nd ed. Boston: Brown and Company; 1991. pp. p. 48–72.
    1. Diggle PJ. An approach to the analysis of repeated measurements. Biometrics. 1988;44(4):959–71.
    1. Hosmer DW, Lemeshow S. New York: Wiley; 1989. Applied Logistic Regression.
    1. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53:457–81.
    1. Cox DR, Oakes D. London: Chapman and Hall; 1984. Analysis of Survival Data. 1st ed.
    1. Cox DR. Regression Models and Life-tables. J Royal Statistical Society. 1972;34(2):187–220.
    1. Mitrovic V, Appel KF, Proskynitopoulos N, Dereli S, Hamm CW. Effects of candesartan cilexetil &ldquo;add-on&rdquo; treatment in congestive heart failure outpatients in daily practice. Clin Res Cardiol. 2009;98(6):379–89.
    1. White M, Lepage S, Lavoie J, De Denus S, Leblanc MH, Gossard D, et al. Effects of combined candesartan and ACE inhibitors on BNP, markers of inflammation and oxidative stress, and glucose regulation in patients with symptomatic heart failure. J Card Fail. 2007;13(2):86–94.
    1. Caccamo MA, Eckman PM. Pharmacologic therapy for New York Heart Association class IV heart failure. Congest Heart Fail. 2011;17(5):213–9.
    1. Packer M, Lee WH, Medina N, Yushak M, Kessler PD. Functional renal insufficiency during long-term therapy with captopril and enalapril in severe chronic heart failure. Ann Intern Med. 1987;106(3):346–54.
    1. Viecili PR, Pamplona D, Park M, Silva SR, Ramires JA, Da Luz PL. Antagonism of the acute hemodynamic effects of captopril in decompensated congestive heart failure by aspirin administration. Braz J Med Biol Res. 2003;36(6):771–80.
    1. Tacon CL, McCaffrey J, Delaney A. Dobutamine for patients with severe heart failure: a systematic review and meta-analysis of randomised controlled trials. Intensive Care Med. 2012;38(3):359–67.
    1. Partovian C, Gleim SR, Mody PS, Li SX, Wang H, Strait KM, et al. Hospital patterns of use of positive inotropic agents in patients with heart failure. J Am Coll Cardiol. 2012;60(15):1402–9.
    1. Follath F, Yilmaz MB, Delgado JF, Parissis JT, Porcher R, Gayat E, et al. Clinical presentation, management and outcomes in the Acute Heart Failure Global Survey of Standard Treatment (ALARM-HF) Intensive Care Med. 2011;37(4):619–26.
    1. Mentz RJ, Felker GM. Natriuretic peptide-guided therapy for heart failure. Circ J. 2011;75(9):2031–7.
    1. Troughton RW, Frampton CM, Yandle TG, Espiner EA, Nicholls MG, Richards AM. Treatment of heart failure guided by plasma aminoterminal brain natriuretic peptide (N-BNP) concentrations. Lancet. 2000;355(9210):1126–30.
    1. Jourdain P, Jondeau G, Funck F, Gueffet P, Le Helloco A, Donal E, et al. Plasma brain natriuretic peptide-guided therapy to improve outcome in heart failure: the STARS-BNP Multicenter Study. J Am Coll Cardiol. 2007;49(16):1733–9.
    1. Berger R, Moertl D, Peter S, Ahmadi R, Huelsmann M, Yamuti S, et al. N-terminal pro-B-type natriuretic peptide-guided, intensive patient management in addition to multidisciplinary care in chronic heart failure a 3-arm, prospective, randomized pilot study. J Am Coll Cardiol. 2010;55(7):645–53.
    1. Konstam MA, Neaton JD, Dickstein K, Drexler H, Komajda M, Martinez FA, et al. Effects of high-dose versus low-dose losartan on clinical outcomes in patients with heart failure (HEAAL study): a randomised, double-blind trial. Lancet. 2009;374(9704):1840–8.
    1. Cice G, Di Benedetto A, D'Isa S, D'Andrea A, Marcelli D, Gatti E, et al. Effects of telmisartan added to Angiotensin-converting enzyme inhibitors on mortality and morbidity in hemodialysis patients with chronic heart failure a double-blind, placebo-controlled trial. J Am Coll Cardiol. 2010;56(21):1701–8.
    1. Yusuf S, Teo KK, Pogue J, Dyal L, Copland I, Schumacher H, et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med. 2008;358(15):1547–59.
    1. Lakhdar R, Al-Mallah MH, Lanfear DE. Safety and tolerability of angiotensin-converting enzyme inhibitor versus the combination of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker in patients with left ventricular dysfunction: a systematic review and meta-analysis of randomized controlled trials. J Card Fail. 2008;14(3):181–8.
    1. Ochiai ME, Barretto AC, Oliveira MT, Jr, Munhoz RT, Morgado PC, Ramires JA. Uric acid renal excretion and renal insufficiency in decompensated severe heart failure. Eur J Heart Fail. 2005;7(4):468–74.

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