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• Authors' response
  James M Beattie
  Published on: 19 April 2016
• o Response to: 1 Subcutaneous furosemide in advanced heart failure: has clinical practice run ahead of the evidence base? James M Beattie, Miriam J Johnson BMJ Support Palliat Care 2012;2:5-6
  Duwarakan K Satchithananda
  Published on: 19 April 2016

• Published on: 19 April 2016

  Authors' response

  • James M Beattie, Consultant Cardiologist
  • Other Contributors:
    • Miriam J Johnson

  We would like to thank Drs Satchithananda, Hookey and Sister Ingram for their interest in our editorial. We welcome this opportunity to respond. We framed our discussion in the setting of left ventricular systolic dysfunction as this is where the robust evidence base for heart failure therapy has evolved. The evidence base for effective therapy for the clinical syndrome of heart failure with preserved systolic functio...

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  We would like to thank Drs Satchithananda, Hookey and Sister Ingram for their interest in our editorial. We welcome this opportunity to respond. We framed our discussion in the setting of left ventricular systolic dysfunction as this is where the robust evidence base for heart failure therapy has evolved. The evidence base for effective therapy for the clinical syndrome of heart failure with preserved systolic function (HFpSF) is much weaker, with very few randomised controlled clinical trials (RCTs). However, we accept that the symptomatic burden and mortality risk for those with HFpSF is comparable, and loop diuretic therapy for the associated dyspnoea and congestion is no less applicable to that clinical cohort. Indeed, differentiating between such sub- populations may be largely irrelevant as many heart failure patients exhibit demonstrable abnormalities of both systolic and diastolic function.

  While there are differences in the assignment of weighting in terms of the class of recommendation and hierarchy of evidence on the conventional use of loop diuretics over the range of acute and chronic heart failure treatment guidelines, and RCTs may be hard to justify ethically, we have an experiential repository of about 40 years of clinical practice with the use of oral and intravenous furosemide across the clinical spectrum of heart failure. Accumulation of this experience underpins clinical judgement and is consistent with the development of so called 'tacit knowledge' which has been proposed as fundamental to evidence base development 1.

  Certainly, individualising patients' dosing regimens with appropriate clinical monitoring is mandated for this therapy to be effective and safe, irrespective of the route of furosemide administration as demonstrated in Diuretic Optimization Strategies Evaluation (DOSE) trial 2. The successful use of this approach specifically for the prescription of subcutaneous (SC) furosemide was apparent in the Scarborough study cited in our editorial in which a wide dosing range was employed 3. This study also demonstrated the effectiveness of multidisciplinary team working, widely accepted as beneficial across the entire heart failure disease trajectory, and no less relevant at the end of life 4. Indeed, the recently published NICE heart failure quality standards require such an approach, integrating the complementary clinical skills of both heart failure and palliative care professionals to support those with moderate to severe heart failure 5.

  The main driver behind our editorial was concern about the largely empirical adoption of SC furosemide by the palliative care community for the treatment of patients dying with heart failure as the primary terminal illness or as a comorbidity without addressing the need for systematic assessment of effectiveness or clinical risk. This use of SC furosemide for some of the sickest heart failure patients challenges the accepted treatment paradigm, but also provides opportunity for formal clinical evaluation, and we welcome the authors' potential contribution to development of the evidence base for this form of therapy.

  James M Beattie

  Department of Cardiology, Heart of England NHS Foundation Trust, Birmingham, UK; National Clinical Advisor, NHS Improvement.

  Miriam J Johnson

  Hull York Medical School, University of Hull; St Catherine's Hospice, Scarborough, UK.

  References

  1. Thornton T. Tacit knowledge as the unifying factor in evidence based medicine and clinical judgement. Philos Ethics Humanit Med. 2006 1:2

  2. Felker GM, Lee KL, Bull DA. et al, Diuretic strategies in patients with acute decompensated heart failure. N Engl J Med 2011; 364:797-805

  3. Zacharias H, Raw J, Nunn A. et al. Is there a role for subcutaneous furosemide in the community and hospice management of end- stage heart failure? Palliat Med 2011,25: 658-63.

  4. Ryder M, Beattie JM, O'Hanlon R. et al. Multidisciplinary heart failure management and end of life care. Curr Opin Support Pall Care 2011, 5: 317-21.

  5. NHS National Institute for Health and Clinical Excellence. Heart failure quality standard, June 2011. Available from http://www.nice.org.uk/guidance/qualitystandards/chronicheartfailure/home.jsp

  (accessed 4 Apr 2012).

  Conflict of Interest:

  None declared

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  Conflict of Interest:
  None declared.

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• Published on: 19 April 2016

  o Response to: 1 Subcutaneous furosemide in advanced heart failure: has clinical practice run ahead of the evidence base? James M Beattie, Miriam J Johnson BMJ Support Palliat Care 2012;2:5-6

  • Duwarakan K Satchithananda, Cardiologist
  • Other Contributors:
    • Angela Ingram and Claire Hookey

  We read the editorial concerning the use of subcutaneous furosemide in heart failure with interest. We feel that there is a substantial opportunity for misinterpretation of the editorial by readers not as familiar with the issues raised as the eminent authors themselves. This particularly relates to: 1 The heart failure syndrome It is important to emphasize that the editorial relates to the treatment of congestive symptom...

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  We read the editorial concerning the use of subcutaneous furosemide in heart failure with interest. We feel that there is a substantial opportunity for misinterpretation of the editorial by readers not as familiar with the issues raised as the eminent authors themselves. This particularly relates to: 1 The heart failure syndrome It is important to emphasize that the editorial relates to the treatment of congestive symptoms in patients suffering with the heart failure syndrome irrespective of its causal mechanism i.e. left ventricular systolic dysfunction is only one of many mechanisms inducing this syndrome i.e.50% of patients hospitalised with heart failure do not have left ventricular systolic dysfunction[1,2]. 2 The use of furosemide in heart failure symptom relief. It is important to recognise that the lack of evidence suggested for subcutaneous furosemide is equally applicable to any route of delivery for furosemide i.e. there are no placebo controlled randomised trials demonstrating the longer term benefits of furosemide (irrespective of its administration route) in terms of morbidity and mortality in heart failure. Indeed there is a discrepancy in the analysis of the evidence for the Grade 1 recommendation for furosemide (i.e. evidence and or general agreement that a treatment or procedure is beneficial, useful and effective) suggested both by American and European guidelines in heart failure. The European Society of Cardiology guideline [3]suggests the level of evidence is 'B' (i.e. limited populations evaluated. Data derived from a single randomised trial or from non-randomised studies) wheras the American Heart Association [1] evaluates the same evidence as 'C' (i.e. very limited populations evaluated. Only consensus opinions of experts, case studies or standards of care).

  3 The efficacy and dosing of subcutaneous furosemide The argument in favour of this practice is clearly documented by the authors . Difficulties in dosing subcutaneous diuretics should be taken within the similar uncertainties existing for the administration of any diuretic irrespective of its route. The most recent (and only randomised large scale trial of diuretics in decompensated heart failure) suggest no substantial clinical difference between dose size or frequency of administration of intravenous diuretics for decompensated heart failure[4]. There is no reason to suspect that this lack of clear efficacy of any single intravenous diuretic regime should not equally apply to subcutaneously administered furosemide. It is additionally not unusual within the evidence based practice of heart failure to extrapolate evidence into populations not represented within that evidence e.g. the majority of ACEI and B blocker trials have populations entirely unrepresentative of clinically encountered populations[5]. 5 Clinical expertise and patient values Heart failure is not a diuretic deficiency disease. Therefore the use of increasing doses of diuretics, their need for titration, measures of their success and the need for other cardiac and non-cardiac interventions to reduce symptoms should all occur within the framework of a multi- disciplinary heart failure programme (irrespective of the route of administration of the augmented diuretic)[1,3]. Our own practice specifically with regard to subcutaneous diuretics is to use professionals skilled in the management of congestive symptoms to regularly titrate the dose of subcutaneous diuretics until a pre-specified goal or end point is reached. Weight reduction is only one feature of this assessment. It should be noted that in a registry of over 100,000 patients hospitalised with heart failure one third of patients lost < 2.3 Kg and 16% gained weight over their entire hospitalisation [2].

  While we agree with the authors that there is a need for further evaluation of the use of subcutaneous fursoemide in the management of advanced heart failure (indeed we are seeking to add to the evidence base in this area), we feel that it may be unhelpful to isolate only this area of heart failure management for comment. We hope that contextualising the editorial's concerns (within the available knowledge of current heart failure practice) will ensure the continued use of this route of administration to afford patients' choice and control in the management of their progressive chronic illness.

  References 1 Hunt SA, Abraham WT, Chin MH, Feldman AM, et al. 2009 Focused update incorporated into the ACC/AHA 2005 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;119:1977-2016, 2 Gheorghiade M, Filippatos G. Reassessing treatment of acute heart failure syndromes: the ADHERE Registry. European Heart Journal Supplements (2005) 7 (Supplement B), B13-B19 3 Dickstein K, Cohen-Solal A, Filippatos G et al. 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 J Heart Fail. 2008 Oct;10(10):933-89. 4 Fonarow GC Comparative Effectiveness of Diuretic Regimens. N Engl J Med 2011; 364:877-878

  5 Mattie J. Lenzen1,*, Eric Boersma1, Wilma J.M. Scholte op Reimer et al. Under-utilization of evidence-based drug treatment in patients with heart failure is only partially explained by dissimilarity to patients enrolled in landmark trials: a report from the Euro Heart Survey on Heart Failure. European Heart Journal (2005) 26, 2706-2713

  Conflict of Interest:

  None declared

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  Conflict of Interest:
  None declared.

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