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2019 - A fruitful year in the field of heart failure

The year 2019 saw the publication of data from a series of trials, the publication of an expert consensus and a focused presentation at the August annual scientific meeting of the European Society of Cardiology (ESC). This information taken together updates several of the points made in the 2016 edition of the ESC’s Acute and Chronic Heart Failure Guidelines. This article summarises some of the new experience and how it might apply to our daily practice.

Heart Failure


On the Expert Consensus

Of the many things that we witnessed in 2019, the most important clinical practice update was published in May by the Heart Failure Association. It is, as the authors emphasise, a summary and a consensus view in the form of consensus recommendations [1].

The most significant aspects of this update are the new recommendations based on the evidence from major trials published since 2016. Here is a list of new data published since that time:

  • Sodium-glucose transport protein 2 (SGLT2) inhibitors in type 2 diabetes mellitus
  • MitraClip for functional mitral regurgitation
  • Atrial fibrillation ablation in heart failure (HF)
  • The use of tafamidis in cardiac transthyretin amyloidosis
  • Rivaroxaban in HF
  • Implantable cordioverter-defibrillators (ICDs) in non-ischaemic HF
  • Telemedicine for HF

The Use of SGLT2 Inhibitors in Patients with Type 2 Diabetes Mellitus

The 2016 Guideline said that empagliflozin (SGLT2 inhibitor) should be considered in patients with type 2 diabetes mellitus (T2DM) “in order to prevent or delay the onset of heart failure or prolong life”.

The 2019 expert consensus recommends that canagliflozin and dapagliflozin (SGLT2 inhibitors) should also be considered for patients with T2DM and either established cardiovascular disease or at high cardiovascular risk in order to prevent or delay the onset of HF and hospitalisations for HF [2, 3]. No specific recommendations are made for the use of SGLT2 inhibitors in patients with established HF and no T2DM yet. [4].

The CANTOS trial

The importance of inflammation in the outcome of coronary patients was evaluated in the CANTOS trial. This trial randomised patients with prior myocardial infarction and elevated C-reactive protein to canakinumab (human monoclonal antibody targeted at interleukin-1 beta) or placebo [5, 6]. Even though the results were positive, evidence is not sufficient to provide a recommendation for its use in patients with HF. The U.S. Food and Drug Administration (FDA) denied regulatory approval for canakinumab for patients with coronary artery disease. A new potential therapeutic area is lung diseases and potentially other forms of cancer. Relevant trials are ongoing [7].

Possible Replacements for ACE-I/ARBs in Ambulatory Patients with HFrEF

Sacubitril/valsartan (ARNI) is recommended as a replacement for angiotensin-converting enzyme inhibitors (ACE-I)/angiotensin receptor blockers (ARBs) to reduce the risk of HF hospitalisation and death in ambulatory patients with heart failure with reduced ejection fraction (HFrEF) who remain symptomatic despite optimal medical treatment with an ACE-I, a beta-blocker (BB) and a mineralocorticoid receptor antagonist (MRA) [8].

Initiation of sacubitril/valsartan (ARNI) rather than an ACE-I or an ARB may be considered for patients hospitalised with acute HF (new-onset  or decompensated HF) to reduce the short-term risk of adverse events and to simplify management by avoiding the need to titrate ACE-I first and then switch to sacubitril/valsartan (ARNI) [9].

Managing Hyperkalaemia in Heart Failure

Patiromer (potassium binder in the gut) and ZS-9 (sodium zirconium cyclosilicate) may be considered in patients with HF with or without chronic kidney disease (CKD) to manage hyperkalaemia. In selected patients these therapies may enable use of MRAs and other renin-angiotensin-aldosterone system (RAASs) blockers in more patients and at higher doses, but it is not known whether this will improve patient outcomes [10, 11].

Patiromer and ZS-9 may be considered in selected patients with HF with or without CKD in order to enable up-titration of MRA while avoiding hyperkalaemia.

Current Heart Failure Drugs Recommended for Use in Ambulatory Patients

A beta-blocker (BB) may be considered for ambulatory patients with symptomatic heart failure with mid-range ejection fraction (HFmrEF) in sinus rhythm in order to reduce the risk of all-cause and cardiovascular (CV) death [12].

Candesartan (ARB) may be considered for ambulatory patients with symptomatic HFmrEF in order to reduce the risk of HF hospitalisation and CV death [13].

Spironolactone (MRA) may be considered for ambulatory patients with symptomatic HFmrEF without contraindications in order to reduce the risk of cardiovascular death and HF hospitalisation [14].

For ambulatory patients with coronary artery disease (CAD) and HF in New York Heart Association (NYHA) Class I/II with an left ventricular ejection fraction (LVEF) greater than 30%, the addition of rivaroxaban (DOAC) 2.5 mg bd to background treatment with aspirin may be considered in order to reduce the risk of stroke and CV death. For HF patients with a recent HF hospitalisation or persistent NYHA Class III/IV, initiation of treatment with rivaroxaban cannot be recommended, as there is no demonstrable benefit. The general agreement for patients with CAD is that rivaroxaban 2.5 mg bd in addition to low-dose aspirin reduces the risk of vascular events in patients without HF and with mild HF. For patients with advanced HF, myocardial dysfunction and congestion determine outcome rather than vascular events.

Trial Results Presented during the ESC Annual Meeting

The star trial of the August 2019 ESC meeting in Paris was undoubtedly the DAPA-HF Trial.

The study drug dapagliflozin (SGLT2 inhibitor) 10 mg once daily added to standard therapy was given in patients with HFrEF with and without T2DM. For the primary composite endpoint CV death, HF hospitalisation and urgent HF visit, dapagliflozin showed a significant reduction compared to placebo [15]. In the light of these results, dapagliflozin offers a new approach to the treatment of HFrEF.

Another important trial presented during the ESC meeting was the PARAGON-HF Trial. It tested the hypothesis that sacubitril/valsartan (ARNI) compared with valsartan (ARB) might reduce the composite outcome of total hospitalisation and CV death in patients with heart failure with preserved ejection fraction (HFpEF). The results failed to show a significant reduction in the primary endpoint. The trial data suggest heterogeneity in treatment response with a possibly better benefit in women and in patients with lower EF rather than higher EF.

End-of-life Care and Heart Failure

An interesting paper published in May 2019 in the Journal of the American College of Cardiology (JACC) showed that during the last year of life patients with HF were more likely to be hospitalised due to non-CV causes than due to HF itself. This finding sheds new light on a multidisciplinary approach in end-of-life care of patients with HF [16].

Everyday Management of Heart Failure

Important aspects regarding the real-life data in the management of HF patients were investigated in the CHAMP-HF Registry. In patients with HFrEF, it was found that more than 90% of patients determined to be eligible for BB and ACE-I/ARB/angiotensin receptor-neprilysin inhibitor (ARNI), and with systolic blood pressure (SBP) >110 mmHg were not receiving target doses of therapies that have previously been shown to reduce morbidity and mortality in HFrEF [17].

The Registry identified some strategies needed to support the use of more effective, guideline-recommended doses of HF medications in patients with HFrEF: intensive education through the electronic medical record, defined protocols, improvements in transition of patients between providers, creation of dosing-based performance measures and patient education [17].

The REGARDS trial offered a robust evidence base for the dietary prevention of HF. The authors found differences in the dietary patterns of those patients with HFpEF compared with those with HFrEF. The trial provides an early glimpse of precision dietary prevention of HF (i.e., recommending dietary approaches customised to HF subtypes with different pathophysiological bases) [18].

Finally, we should mention a report published early in 2019 from four European cohorts demonstrating that the measures which make sense for the health of the general population and the prevention of CV disease also makes sense for HF prevention. The challenge for us today is to ensure the effective implementation of such measures in the general population and at an individual level in order to keep control throughout life of such critical issues as body weight, blood pressure, diabetes and cigarette smoking [19].

Conclusion

The advances witnessed in 2019 in the field of HF offer new options in the treatment of HF on many levels. They concern specific disease states, but also the overall management of our patients, from providing more effective end-of-life care to preventing disease by embracing healthy lifestyles. 

References


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  3. Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, Shaw W, Law G, Desai M, Matthews DR; CANVAS Program Collaborative Group. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med. 2017;377:644-657. 
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  6. Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, Fonseca F, Nicolau J, Koenig W, Anker SD, Kastelein JJP, Cornel JH, Pais P, Pella D, Genest J, Cifkova R, Lorenzatti A, Forster T, Kobalava Z, Vida-Simiti L, Flather M, Shimokawa H, Ogawa H, Dellborg M, Rossi PRF, Troquay RPT, Libby P, Glynn RJ; CANTOS Trial Group. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. N Engl J Med. 2017;377:1119-31. 2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dwww.ncbi.nlm.nih.gov
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  17. Peri-Okonny, Mi X, Khariton Y, Patel K, Thomas L, Fonarow GC, Sharma PP, Duffy C, Albert NM, Butler J, Hernandez AF, McCague K, Williams FB, DeVore AD, Patterson JH, Spertus JA. Target Doses of Heart Failure Medical Therapy and Blood Pressure: Insights From the CHAMP-HF Registry. JACC Heart Fail. 2019;7:350-358. 
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  19. Cowie MR, Zakeri R. Preventing Heart Failure at the Population Level: Conventional Cardiovascular Risk Factor Management Should Continue. JACC Heart Fail. 2019;7:214-216. 

Notes to editor


Author:

Ruxandra Christodorescu, MD, PhD, FESC

Senior Consultant Cardiology and Internal Medicine

Immediate past president Working Group on Heart Failure, Romanian Society of Cardiology

Board member Romanian Society of Cardiology

Senior Lecturer University of Medicine and Pharmacy Victor Babes Timisoara

Affiliation:

University of Medicine and Pharmacy Victor Babes Timisoara, Romania

 

 

Address for correspondence:

Dr Ruxandra Christodorescu, The City Hospital,Cardiology ASCAR, Bd. Revolutiei nr.12, 300024 Timisoara, Romania       

E-mail: ruxandra_christodorescu@yahoo.com

 

 

Author disclosure: 

Speaker fee from: Novartis, Servier, Boeringer Ingelheim, Sanofi, Pfizer

 

 

 

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.