Journal Information
Vol. 37. Issue 6.
Pages 497-498 (June 2018)
Vol. 37. Issue 6.
Pages 497-498 (June 2018)
Editorial comment
Open Access
Sacubitril-valsartan in the real world: From theory to clinical practice
Uso do Sacubitril/Valsartan no “mundo real”: da teoria à prática clínica
Visits
5500
Ricardo Fontes-Carvalhoa,b
a Departamento de Cardiologia, Centro Hospitalar de Vila Nova de Gaia, Vila Nova de Gaia, Portugal
b Departamento de Fisiologia e Cirurgia Cardiotoracia, Faculdade de Medicina, Universidade do Porto, Porto, Portugal
This item has received

Under a Creative Commons license
Article information
Full Text
Bibliography
Download PDF
Statistics
Full Text

“In theory, theory and practice are the same. In practice, they are not.” – Albert Einstein

Heart failure (HF) is considered the new cardiovascular epidemic of the 21st century, in view of its increasing prevalence, high mortality and enormous costs.1 In Portugal, HF is a major public health problem for which local and national measures are urgently needed in order to change how HF-related healthcare is currently organized.2

Pharmacological treatment for heart failure with reduced ejection fraction (HFrEF) is based on careful titration of disease-modifying drugs, such as angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs), beta-blockers and aldosterone antagonists.3 Recently, the PARADIGM-HF study showed that the use of sacubitril-valsartan reduced the risk of cardiovascular events by a further 20%4 compared to ACE inhibitors and that this new strategy of neurohumoral modulation, instead of merely inhibition, increased survival by one to two years in patients with HFrEF.5

Given the good results of the PARADIGM-HF study, the use of sacubitril-valsartan has been included in the European Society of Cardiology guidelines as a class IB recommendation in patients who remain symptomatic despite optimal treatment.3 The latest American guidelines for HF treatment have gone even further, recommending that patients in New York Heart Association (NYHA) class II or III who tolerate an ACE inhibitor or ARB be switched to sacubitril-valsartan to further reduce the risk of HF-related morbidity and mortality.6

However, despite the abundance of evidence and the recommendations in the guidelines, uptake of sacubitril-valsartan in the real world has been disappointingly slow.7 There are various reasons for this mismatch between theory (the guidelines) and clinical practice, one of which is that patients included in clinical trials may not be representative of the real-world population. In a study examining this question by Rodrigues et al.8 published in this issue of the Journal, only one in four patients with HFrEF followed in the HF clinic of a Portuguese tertiary hospital met the inclusion criteria of the PARADIGM-HF trial. Similarly, a study investigating the same issue that analyzed over 6000 consecutive patients referred to an HF clinic in the UK showed that only 21% fulfilled the PARADIGM-HF criteria,9 although this proportion increased to 60% if the need to reach the maximum ACE inhibitor/ARB doses was ignored. These findings reveal that in many HF patients doses of ACE inhibitors/ARBs are not titrated to the maximum recommended, either because of the presence of hypotension, renal failure or other comorbidities, or due to clinical inertia in titrating drug doses in HF.

It is thus important to discuss whether titrating drugs up to the maximum dose should be mandatory before considering initiating sacubitril-valsartan. In the PARADIGM-HF trial, the benefits of the latter drug were consistent, regardless of dose or background therapy.10 In addition, around 40% of patients had to have their enalapril dose reduced during the trial, and treatment benefits were similar in these individuals.11 Thus, since the survival benefits of sacubitril-valsartan exceed those of an increase in ACE inhibitor/ARB dose, even patients taking submaximal doses of ACE inhibitors or ARBs should be switched to equivalent doses of sacubitril-valsartan.12

In conclusion, the introduction of sacubitril-valsartan is undeniably an advance in the treatment of HFrEF.13 It is indicated as a replacement for ACE inhibitors/ARBs in HF patients with ejection fraction <40% and in NYHA class II-III. In HF, delay in starting disease-modifying treatment is associated with a significant increase in mortality.14,15 Therefore, in the knowledge that (especially in medicine) theory and practice, as Einstein pointed out, are often not the same, the success of HF treatment will depend on whether the best scientific evidence is applied in real-world clinical practice.

Conflicts of interest

The author has no conflicts of interest to declare.

References
[1]
C. Fonseca, D. Brás, I. Araújo, et al.
Heart failure in numbers: estimates for the 21st century in Portugal.
Rev Port Cardiol, 37 (2018), pp. 97-104
[2]
C. Fonseca, D. Brito, R. Cernadas, et al.
Consensus document on improvement of heart failure treatment in Portugal.
Rev Port Cardiol, 36 (2017), pp. 1-8
[3]
P. Ponikowski, A.A. Voors, S.D. Anker, et al.
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, 37 (2016), pp. 2129-2200
[4]
J.J.V. McMurray, M. Packer, A.S. Desai, et al.
Angiotensin-neprilysin inhibition versus enalapril in heart failure.
N Engl J Med, 371 (2014), pp. 993-1004
[5]
B. Claggett, M. Packer, J.J. McMurray, et al.
Estimating the long-term treatment benefits of sacubitril-valsartan.
N Engl J Med, 373 (2015), pp. 2289-2290
[6]
C.W. Yancy, M. Jessup, B. Bozkurt, et al.
2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America.
J Am Coll Cardiol, 70 (2017), pp. 776-803
[7]
N. Luo, G.C. Fonarow, S.J. Lippmann, et al.
Early adoption of sacubitril/valsartan for patients with heart failure with reduced ejection fraction: insights from Get With the Guidelines-Heart Failure (GWTG-HF).
JACC Heart Fail, 5 (2017), pp. 305-309
[8]
G. Rodrigues, A. Tralhão, C. Aguiar, et al.
Será a coorte do PARADIGM-HF representativa da população do mundo real de doentes com insuficiência cardíaca?.
Rev Port Cardiol, 37 (2018), pp. 491-496
[9]
P. Pellicori, A. Urbinati, P. Shah, et al.
What proportion of patients with chronic heart failure are eligible for sacubitril-valsartan?.
Eur J Heart Fail, 19 (2017), pp. 768-778
[10]
N. Okumura, P.S. Jhund, J. Gong, et al.
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, 9 (2016),
pii:e003212
[11]
O. Vardeny, B. Claggett, M. Packer, et al.
Efficacy of sacubitril/valsartan vs. enalapril at lower than target doses in heart failure with reduced ejection fraction: the PARADIGM-HF trial.
Eur J Heart Fail, 18 (2016), pp. 1228-1234
[12]
M. Packer.
Love of angiotensin-converting enzyme inhibitors in the time of cholera.
[13]
P. Marques da Silva, C. Aguiar.
Sacubitril/valsartan: an important piece in the therapeutic puzzle of heart failure.
Rev Port Cardiol, 36 (2017), pp. 655-668
[14]
S. Zaman, S.S. Zaman, T. Scholtes, et al.
The mortality risk of deferring optimal medical therapy in heart failure: a systematic comparison against norms for surgical consent and patient information leaflets.
Eur J Heart Fail, 19 (2017), pp. 1401-1409
[15]
G.C. Fonarow, A.F. Hernandez, S.D. Solomon, et al.
Potential mortality reduction with optimal implementation of angiotensin receptor neprilysin inhibitor therapy in heart failure.
JAMA Cardiol, 1 (2016), pp. 714-717

Please cite this article as: Fontes-Carvalho R. Uso do Sacubitril/Valsartan no “mundo real”: da teoria à prática clínica. Rev Port Cardiol. 2018;37:497–498.

Copyright © 2018. Sociedade Portuguesa de Cardiologia
Idiomas
Revista Portuguesa de Cardiologia (English edition)
Article options
Tools
en pt

Are you a health professional able to prescribe or dispense drugs?

Você é um profissional de saúde habilitado a prescrever ou dispensar medicamentos

By checking that you are a health professional, you are stating that you are aware and accept that the Portuguese Journal of Cardiology (RPC) is the Data Controller that processes the personal information of users of its website, with its registered office at Campo Grande, n.º 28, 13.º, 1700-093 Lisbon, telephone 217 970 685 and 217 817 630, fax 217 931 095, and email revista@spc.pt. I declare for all purposes that the information provided herein is accurate and correct.