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Management of a Multicomorbid Patient with Heart Failure

Magri G.a · Bentivenga C.a · Cosentino E.R.a · Degli Esposti D.a · Borghi C.a · Dormi A.b

Author affiliations

aInternal Medicine Unit (Dir. C. Borghi) and bMedical Statistics and Clinical Epidemiology, Medical and Surgical Sciences Department, University of Bologna, Bologna, Italy

Corresponding Author

Gianluigi Magri, MD, PhD

DIMEC, UO Borghi, pad.2, Pol.S.Orsola-Malpighi

via Massarenti 9

IT-40138 Bologna (Italy)

E-Mail gianluigi.magri@unibo.it

Related Articles for ""

Cardiology 2017;138(suppl 1):21-23

Abstract

The optimal use of sacubitril/valsartan in clinical practice needs further investigation, in particular for patients with multiple comorbidities, as such patients are usually poorly represented in clinical trials. To this end, well-documented case reports may add further evidence to the bulk of “field practice” experience on sacubitril/valsartan. We report here the case of a patient with heart failure with reduced ejection refraction with multiple comorbidities treated with sacubitril/valsartan. Overall, sacubitril/valsartan led to a prompt (within a few months) improvement in LVEF (+15%, from 38 to 53%), without any noticeable adverse events. This therapy also allowed the patient to discontinue furosemide.

© 2017 S. Karger AG, Basel


Introduction

The 2016 guidelines issued by the European Society of Cardiology (ESC) state that treatment of heart failure (HF) aims at improving the patient's clinical status, functional capacity, and quality of life, as well as preventing hospital admission and reducing mortality [1]. To this end, neurohormonal antagonists (ACE inhibitors, mineralocorticoid receptor antagonists, and beta-blockers) prolong survival in HF patients with reduced ejection fraction (HFrEF) and are therefore recommended in this setting [1].

In recent years, a new compound that combines the moieties of an angiotensin-receptor blocker (valsartan) and a neprilysin inhibitor (sacubitril) was superior over an ACE inhibitor, enalapril, in reducing the risk of death and HF-related hospitalization during the pivotal double-blind PARADIGM-HF trial [2]. Indeed, the trial was stopped early (median follow-up of 27 months) due to the superiority of sacubitril/valsartan: at study closure, the primary outcome - a composite of death from cardiovascular causes or hospitalization for heart failure - had occurred in 914 patients (21.8%) on sacubitril/valsartan and 1,117 patients (26.5%) in the enalapril group (p < 0.001). Moreover, sacubitril/valsartan was superior to enalapril also in terms of mortality for any cause (17% vs. 19.8%) and cardiovascular mortality (13.3% vs. 16.5%) (p < 0.001 for both comparisons). Following these landmark results, the ESC guidelines now recommend sacubitril/valsartan to replace ACE inhibitors in ambulatory HFrEF patients who remain symptomatic despite optimal therapy and who fit trial criteria (evidence level, IB) [1].

However, the optimal use of sacubitril/valsartan in clinical practice needs further investigation, in particular with reference to patients with multiple comorbidities, who are poorly represented in clinical trials [1,3,4,5]. In this line, well-documented case reports may add further evidence to the “field practice” experience with sacubitril/valsartan. We report here the case of an HFrEH patient with multiple comorbidities treated with sacubitril/valsartan.

Case Presentation

This was the case of a 62-year-old patient. He presented with class II obesity (184 cm, 128 kg, BMI 37.8), with a history of smoking (50 cigarettes/day for 15 years), moderate alcohol consumption, and familial history of cardiovascular disease. He had been affected by the metabolic syndrome for the previous 15 years (hypertension, hypercholesterolemia, hypertriglyceridemia, hyperuricemia, poor glucose tolerance), pharmacologically treated with amlodipine (5 mg/day), doxazosin (2 mg/day), ramipril (10 mg/day), atorvastatin (20 mg/day), omega-3 fatty acids (1 g/day), and allopurinol (300 mg/day).

At the beginning of 2010, the patient experienced insomnia and edema. Treatment with diuretics provided no benefit and therefore the patient - a physician himself - was hospitalized 36 h after the onset of symptoms. Left ventricular ejection fraction (LVEF) was 26% and became 34% after the diuretic aggressive treatment. Once discharged, the patient started treatment with bisoprolol (1.25 mg/day titrated up to 5 g/day), metformin (850 mg b.i.d.), a hypocaloric diet, furosemide (250 mg/day), ramipril (10 mg/day), canrenoate (50 mg/day), and aspirin (100 mg/day). Forty days after discharge, the patient showed improved metabolic parameters, but almost unchanged LVEF (38%). A coronary angiography, followed by revascularization, was then performed. The right coronary artery showed a complete occlusion (>4 cm) but efficient collateral vascularization, and the left coronary artery needed the application of two medicated stents on stenosis >70%. Thirty days later, LVEF increased to 55%. Bisoprolol was gradually increased to 10 mg/day (reducing and then suspending diuretic therapy), but this therapy was associated with mild asthenia.

Therapeutic conditions remained stable until June 2015, when the patient was diagnosed with a leiomyosarcoma of the left thigh, treated with neoadjuvant chemotherapy (epirubicin + ifosfamide) and radiotherapy before surgery. Due to the chemotherapy regimen, atorvastatin and allopurinol were suspended, and the ramipril dosage was reduced (5 mg/day). After surgical removal of the tumor, prior pharmacological treatment was slowly reinstituted.

In March 2016, the patient reported severe asthenia. Laboratory examination revealed hypercholesterolemia (317 mg/dL), high inflammation markers, and sideropenia. This condition persisted up to June 2016, when ECG showed dilated cardiomyopathy, moderate mitral insufficiency, and decreased LVEF (34%). Furosemide (25 mg b.i.d.) and canrenoate (50 mg/day) were added to the pharmacological therapy. After 10 days, a modest increase of LVEF was reported (38%).

Ramipril therapy was then stopped and the patient was switched to sacubitril/valsartan (LCZ696) at the starting dosage of 49/51 mg b.i.d. to test the response. Over a period of 10 days, furosemide therapy was suspended (after reduction of dosage to 25 mg/day) and treatment with ezetimibe/simvastatin 10/20 mg/day replaced atorvastatin. The patient reported marked diuresis and improved mitral insufficiency; LVEF increased to 53% (October 2016). Given the favorable outcomes observed and the lack of adverse events, sacubitril/valsartan therapy was increased to 97/103 mg b.i.d.; the patient is still under therapy at the time of the drafting of the present manuscript (October 2017).

Clinical Relevance

In this patient, according to European guidelines, the lack of success of traditional “best treatment” suggested trying the approach with sacubitril/valsartan [1]. We probably also had to face the toxicity of chemotherapy treatment and so-called sequelae.

We believe that the case described above provides relevant “field practice” evidence on the comprehensive management of a difficult-to-treat patient with HFrEF and multiple comorbidities. This patient may not have been included in a clinical trial, but he may be considered to represent a paradigmatic patient observed in daily practice. Importantly, therapy with sacubitril/valsartan led to a prompt (within a few months) improvement in LVEF (+15%, from 38% to 53%), without any noticeable adverse events. This therapy also allowed the patient to discontinue furosemide.

Although the present case provides anecdotal evidence, we believe that it does support the effectiveness of sacubitril/valsartan, an intervention that is changing the treatment scenario for HF [6].

Acknowledgements

Editorial assistance for the preparation of this paper was provided by Luca Giacomelli, PhD, on behalf of Content Ed Net; this assistance was funded by Novartis.

Conflict of Interest

The authors have no conflict of interest to declare.


References

  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 J Heart Fail 2016;18:891-975.
  2. McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR; PARADIGM-HF Investigators and Committees: Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med 2014;371:993-1004.
  3. Callan PD, Clark AL: Heart failure - what's new and what's changed? Clin Med (Lond) 2016;16(suppl 6):s37-s42.
  4. Farmakis D, Bistola V, Karavidas A, Parissis J: Practical considerations on the introduction of sacubitril/valsartan in clinical practice: current evidence and early experience. Int J Cardiol 2016;223:781-784.
  5. Okumura N, Jhund PS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Swedberg K, Zile MR, Solomon SD, Packer M, McMurray JJ; PARADIGM-HF Investigators and Committees: Effects of sacubitril/valsartan in the PARADIGM-HF Trial (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) according to background therapy. Circ Heart Fail 2016;9: pii: e003212.
  6. Latini R, Masson S, Staszewsky L: Heart failure trials on pharmacological therapy in 2015: lessons learned and future outlook. Expert Rev Cardiovasc Ther 2016;14:703-711.

Author Contacts

Gianluigi Magri, MD, PhD

DIMEC, UO Borghi, pad.2, Pol.S.Orsola-Malpighi

via Massarenti 9

IT-40138 Bologna (Italy)

E-Mail gianluigi.magri@unibo.it


Article / Publication Details

First-Page Preview
Abstract of  

Published online: December 21, 2017
Issue release date: December 2017

Number of Print Pages: 3
Number of Figures: 0
Number of Tables: 0

ISSN: 0008-6312 (Print)
eISSN: 1421-9751 (Online)

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References

  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 J Heart Fail 2016;18:891-975.
  2. McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR; PARADIGM-HF Investigators and Committees: Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med 2014;371:993-1004.
  3. Callan PD, Clark AL: Heart failure - what's new and what's changed? Clin Med (Lond) 2016;16(suppl 6):s37-s42.
  4. Farmakis D, Bistola V, Karavidas A, Parissis J: Practical considerations on the introduction of sacubitril/valsartan in clinical practice: current evidence and early experience. Int J Cardiol 2016;223:781-784.
  5. Okumura N, Jhund PS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Swedberg K, Zile MR, Solomon SD, Packer M, McMurray JJ; PARADIGM-HF Investigators and Committees: Effects of sacubitril/valsartan in the PARADIGM-HF Trial (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) according to background therapy. Circ Heart Fail 2016;9: pii: e003212.
  6. Latini R, Masson S, Staszewsky L: Heart failure trials on pharmacological therapy in 2015: lessons learned and future outlook. Expert Rev Cardiovasc Ther 2016;14:703-711.