Rationale and study design of intravenous loop diuretic administration in acute heart failure: DIUR-AHF

Alberto Palazzuoli, Gaetano Ruocco, Giorgio Vescovo, Roberto Valle, Salvatore Di Somma, Ranuccio Nuti, Alberto Palazzuoli, Gaetano Ruocco, Giorgio Vescovo, Roberto Valle, Salvatore Di Somma, Ranuccio Nuti

Abstract

Aims: Although loop diuretics are the most commonly used drugs in acute heart failure (AHF) treatment, their short-term and long-term effects are relatively unknown. The significance of worsening renal function occurrence during intravenous treatment is not clear enough. This trial aims to clarify all these features and contemplate whether continuous infusion is better than an intermittent strategy in terms of decongestion efficacy, diuretic efficiency, renal function, and long-term prognosis.

Methods and results: This is a prospective, multicentre, randomized study that compares continuous infusion to intermittent infusion and a low vs. high diuretic dose of furosemide in patients with a diagnosis of acute heart failure, BNP ≥ 100 pg/mL, and specific chest X-ray signs. Randomization criteria have been established at a 1:1 ratio using a computer-generated scheme of either twice-daily bolus injection or continuous infusion for a time period ranging from 72 to 120 h. The initial dose will be 80 mg/day of intravenous furosemide and, in the case of poor response, will be doubled using an escalation algorithm. A high diuretic dose is defined as a furosemide daily amount >120 mg/day respectively.

Conclusions: Continuous and high dose groups could reveal a more intensive diuresis and a greater decongestion with respect to intermittent and low dose groups; high dose and poor loop diuretic efficiency should be related to increased diuretic resistance, renal dysfunction occurrence, and greater congestion status. Poor diuretic response will be associated with less decongestion and an adverse prognosis.

Trial registration: ClinicalTrials.gov NCT02638142.

Keywords: Acute heart failure; Diuretic efficiency; Loop diuretics; Outcome; Renal function; Treatment.

© 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Figures

Figure 1
Figure 1
Study design describing timing assessment before and after treatment and follow‐up evaluation.
Figure 2
Figure 2
Scheme of diuretics dose administration by escalation algorithm based on diuretic response.

References

    1. Ahmed A, Young JB, Love TE, Levesque R, Pitt B. A propensity matched study of the effects of chronic diuretic therapy on mortality and hospitalization in older adults with heart failure. Int J Cardiol 2008; 125: 246–253.
    1. Felker GM, Lee KL, Bull DA, Redfield MM, Stevenson LW, Goldsmith SR, LeWinter MM, Deswal A, Rouleau JL, Ofili EO, Anstrom KJ, Hernandez AF, McNulty SE, Velazquez EJ, Kfoury AG, Chen HH, Givertz MM, Semigran MJ, Bart BA, Mascette AM, Braunwald E, O'Connor CM. Diuretic strategies in acute decompensated heart failure. N Engl J Med 2011; 364: 797–805.
    1. Salvador DR, Rey NR, Ramos GC, Punzalan FE. Continuous infusion versus bolus injection of loop diuretics in congestive heart failure. Cochrane Database Syst Rev 2005; 3: CD003178.
    1. Ter Maaten JM, Dunning AM, Valente MA, Damman K, Ezekowitz JA, Califf RM, Starling RC, van der Meer P, O'Connor CM, Schulte PJ, Testani JM, Hernandez AF, Tang WH, Voors AA. Diuretic response in acute heart failure—an analysis from ASCEND‐HF. Am Heart J 2015; 170: 313–321.
    1. Voors AA, Davison BA, Teerlink JR, Felker GM, Cotter G, Filippatos G, Greenberg BH, Pang PS, Levin B, Hua TA, Severin T, Ponikowski P, Metra M. RELAX‐AHF Investigators. Diuretic response in patients with acute decompensated heart failure: characteristics and clinical outcome—an analysis from RELAX‐AHF. Eur J Heart Fail 2014; 16: 1230–1240.
    1. Palazzuoli A, Pellegrini M, Ruocco G, Martini G, Franci B, Campagna MS, Gilleman M, Nuti N, McCullough PA, Ronco C. Continuous versus bolus intermittent loop diuretic infusion in acutely decompensated heart failure: a prospective randomized trial. Crit Care 2014; 18: R134.
    1. Gheorghiade M, Follath F, Ponikowski P, Barsuk JH, Blair JE, Cleland JG, Dickstein K, Drazner MH, Fonarow GC, Jaarsma T, Jondeau G, Sendon JL, Mebazaa A, Metra M, Nieminen M, Pang PS, Seferovic P, Stevenson LW, van Veldhuisen DJ, Zannad F, Anker SD, Rhodes A, McMurray JJ, Filippatos G, European Society of Cardiology , European Society of Intensive Care Medicine . Assessing and grading congestion in acute heart failure: a scientific statement from the acute heart failure committee of the heart failure association of the European Society of Cardiology and endorsed by the European Society of Intensive Care Medicine. Eur J Heart Fail 2010; 12: 423–433.
    1. Palazzuoli A, Testani JM, Ruocco G, Pellegrini M, Ronco C, Nuti R. Different diuretic dose and response in acute decompensated heart failure: clinical characteristics and prognostic significance. Int J Cardiol 2016; 224: 213–219.
    1. Testani JM, Brisco MA, Turner JM, Spatz ES, Bellumkonda L, Parikh CR, Tang WH. Loop diuretic efficiency: a metric of diuretic responsiveness with prognostic importance in acute decompensated heart failure. Circ Heart Fail 2014; 7: 261–270.
    1. Levey AS, Coresh J, Greene T, Stevens LA, Zhang YL, Hendriksen S, Kusek JW, Van Lente F. Chronic Kidney Disease Epidemiology Collaboration. Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med 2006; 145: 247–254.
    1. Damman K, Testani JM. The kidney in heart failure: an update. Eur Heart J 2015; 36: 1437–1444.
    1. Felker GM, O'Connor CM, Braunwald E. Loop diuretics in acute decompensated heart failure: necessary? Evil? A necessary evil? Circ Heart Fail 2009; 2: 56–62.
    1. Gupta S, Neyses L. Diuretic usage in heart failure: a continuing conundrum in 2005. Eur Heart J 2005; 26: 644–649.
    1. Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, Falk V, González‐Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GM, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P, Authors/Task Force Members , Document Reviewers . 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J 2016; 37: 2129–2200.
    1. Peacock WF, Costanzo MR, De Marco T, Lopatin M, Wynne J, Mills RM, Emerman CL. ADHERE Scientific Advisory Committee and Investigators. Impact of intravenous loop diuretics on outcomes of patients hospitalized with acute decompensated heart failure: insights from the ADHERE registry. Cardiology 2009; 113: 12–19.
    1. Chuen MJ, MacFadyen RJ. Dose‐dependent association between use of loop diuretics and mortality in advanced systolic heart failure. Am J Cardiol 2006; 98: 1416–1417.
    1. Abdel‐Qadir HM, Tu JW, Yun L, Austin PC, Newton GE, Lee DS. Diuretic dose and long‐term outcome in elderly patients with heart failure after hospitalization. Am Heart J 2010; 160: 264–271.
    1. Metra M, Davison B, Bettari L, Sun H, Edwards C, Lazzarini V, Piovanelli B, Carubelli V, Bugatti S, Lombardi C, Cotter G, Dei CL. Is worsening renal function an ominous prognostic sign in patients with acute heart failure? The role of congestion and its interaction with renal function. Circ Heart Fail 2012; 5: 54–62.
    1. Lala A, McNulty SE, Mentz RJ, Dunlay SM, Vader JM, AbouEzzeddine OF, DeVore AD, Khazanie P, Redfield MM, Goldsmith SR, Bart BA, Anstrom KJ, Felker GM, Hernandez AF, Stevenson LW. Relief and recurrence of congestion during and after hospitalization for acute heart failure: insights from Diuretic Optimization Strategy Evaluation in Acute Decompensated Heart Failure (DOSE‐AHF) and Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARESS‐HF). Circ Heart Fail 2015; 8: 741–748.
    1. Hasselblad V, Stough WG, Shah MR, Lokhnygina Y, O'Connor CM, Califf RM, Adams KF Jr. Relation between dose of loop diuretics and outcomes in heart failure population: results of the ESCAPE trial. Eur J Heart Fail 2007; 9: 1064–1069.
    1. Heart Failure Society of America . Evaluation and management of patients with acute decompensated heart failure. J Card Fail 2006; 12: e86–e103.
    1. Butler J, Forman DE, Abraham WT, Gottlieb SS, Loh E, Massie BM, O'Connor CM, Rich MW, Stevenson LW, Wang Y, Young JB, Krumholz HM. Relationship between heart failure treatment and development of worsening renal function among hospitalized patients. Am Heart J 2004; 147: 331–338.
    1. Valente MA, Voors AA, Damman K, Van Veldhuisen DJ, Massie BM, O'Connor CM, Metra M, Ponikowski P, Teerlink JR, Cotter G, Davison B, Cleland JG, Givertz MM, Bloomfield DM, Fiuzat M, Dittrich HC, Hillege HL. Diuretic response in acute heart failure: clinical characteristics and prognostic significance. Eur Heart J 2014. May 14; 35: 1284–1293.
    1. Palazzuoli A, Ruocco G, Ronco C, McCullough PA. Loop diuretics in acute heart failure: beyond the decongestive relief for the kidney. Crit Care 2015; 19: 296.
    1. Yilmaz MB, Gayat E, Salem R, Lassus J, Nikolaou M, Laribi S, Parissis J, Follath F, Peacock WF, Mebazaa A. Impact of diuretic dosing on mortality in acute heart failure using a propensity matched study. Eur J Heart Fail 2011; 13: 1244–1252.

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