Aims The poor control of symptoms in patients with advanced heart failure with reduced ejection function (HFrEF) can limit
the functionality of patients. Sacubitril–valsartan, compared with enalapril, has been shown to reduce mortality and hospitalization, and nowadays, there is still little evidence about the improvement on functionality. The aim of our study is to analyse
the improvement of the functional class and the 6 min walking test (6MWT) in patients with multiple pathologies and
advanced heart failure.
Methods and results From September 2016 to March 2018, 65 multimorbidity patients with severe symptomatic HFrEF
were initiated to receive sacubitril–valsartan. Mean age was 78.6 ± 7.4 years, and 68% were male. The Charlson
co-morbidity index was 8 points. Seventy-four per cent had New York Heart Association (NYHA) Functional Class IV. After
the treatment, patients were able to achieve 55.68 m or more on 6MWT, and 91% presented an improvement in the NYHA
functional class.
Conclusions Sacubitril–valsartan relieves symptoms and improves functional class prognostic risk of patients with advanced
HFrEF and co-morbidit

Malafarina, V. (Vincenzo)

Rodil-Fraile, R. (Raquel)

Tiberio-López, T. (Tiberio)

English

Dadun, University of Navarra

Sacubitril–valsartan in heart failure andmultimorbidity patientsRaquel Rodil Fraile1* , Vincenzo Malafarina2,3 and Gregorio Tiberio López11Internal Medicine Department, Chronic-Multimorbidity Unit, Complejo Hospitalario de Navarra, Irunlarrea, 34, 31008, Pamplona, Spain; 2Geriatric Department,Chronic-Multimorbidity Unit, Complejo Hospitalario de Navarra, Irunlarrea, 34, 31008, Pamplona, Spain; 3Department of Nutrition, Food Science and Physiology, Faculty ofPharmacy and Nutrition, University of Navarra, 31008, Pamplona, SpainAbstractAims The poor control of symptoms in patients with advanced heart failure with reduced ejection function (HFrEF) can limitthe functionality of patients. Sacubitril–valsartan, compared with enalapril, has been shown to reduce mortality and hospital-ization, and nowadays, there is still little evidence about the improvement on functionality. The aim of our study is to analysethe improvement of the functional class and the 6 min walking test (6MWT) in patients with multiple pathologies andadvanced heart failure.Methods and results From September 2016 to March 2018, 65 multimorbidity patients with severe symptomatic HFrEFwere initiated to receive sacubitril–valsartan. Mean age was 78.6 ± 7.4 years, and 68% were male. The Charlsonco-morbidity index was 8 points. Seventy-four per cent had New York Heart Association (NYHA) Functional Class IV. Afterthe treatment, patients were able to achieve 55.68 m or more on 6MWT, and 91% presented an improvement in the NYHAfunctional class.Conclusions Sacubitril–valsartan relieves symptoms and improves functional class prognostic risk of patients with advancedHFrEF and co-morbidity.Keywords Sacubitril–valsartan; Elderly; Multimorbidity; Six-minute walking test; NYHA; MAGGIC scoreReceived: 16 May 2018; Accepted: 22 June 2018*Correspondence to: Raquel Rodil Fraile, Internal Medicine Department, Chronic-Multimorbidity Unit, Complejo Hospitalario de Navarra, Irunlarrea, 34, 31008 Pamplona,Spain. Email: raklrf@hotmail.comIntroductionHeart failure (HF) is a progressive illness that is highly preva-lent among the elderly. Multimorbidity, defined as the co-occurrence of two or more chronic conditions, is a commoncondition in adults, and the prevalence increases with age.1Multimorbidity increases the risk of adverse outcomes suchas declining functional status, hospitalizations, and death,1the same as HF.2,3 There is important recognition to considerco-morbidity in treatment decision because co-morbidity inmultimorbidity patients with HF may worsen its managementand prognosis.4The PARADIGM-HF (Prospective Comparison of ARNI withan ACE-Inhibitor to Determine Impact on Global Mortalityand Morbidity in Heart Failure) trial5 showed thatsacubitril–valsartan reduced the risk of cardiovascular deathor first hospitalization for HF. But there is little evidenceregarding the study of the functionality of patients aftertreatment,6,7 and there is little evidence of the drug in elderlypatients with multimorbidity.8The aim of this study is to evaluate if the use of sacubitril–valsartan improves functionality in multimorbidity patientswith HF and the factors and prognostic tests in elderlypatients with advanced HF and multimorbidity.MethodsStudy populationIn this observational study, we included all HF with reducedejection function (HFrEF) patients assessed in the Chronic-Multimorbidity Unit of the Complejo Hospitalario de Navarrain the period from September 2016 to March 2018.SHORT COMMUNICAT ION© 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.ESC HEART FAILUREESC Heart Failure 2018; 5: 957–960Published online 24 July 2018 in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/ehf2.12338This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium,provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. 20555822, 2018, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/ehf2.12338 by Universidad de Navarra, Wiley Online Library on [19/11/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons LicenseThe Chronic-Multimorbidity Unit performs the assessmentand monitoring of patients with two or more chronic medicalconditions (ischaemic cardiomyopathy, diabetes, chronickidney disease, HF, chronic obstructive pulmonary disease,dementia).We included patients with HFrEF diagnosis in based on theguidelines of European Society of Cardiology on 2016 andwho had dyspnoea at rest or with minimal or slight limitationon physical activity.The clinical history data were acquired in relation to thedata obtained in the usual medical visit of each patient.Follow-up clinical visits were made on the basis of the clinicalevolution of the patient.Complete medical history with clinical variables (bloodpressure, medication, results of echocardiography), labora-tory values (creatinine, albumin, glycosylated haemoglobin[HbA1c], troponin T, brain natriuretic peptide levels),Barthel index, and 6 min walking test (6MWT) was obtainedat the beginning and end of the study period. The New YorkHeart Association (NYHA) scale assessment was performedin each of the consultations made throughout the follow-up. The MAGGIC (Meta-Analysis Global Group in ChronicHeart Failure) score was calculated in the first consultationand prior to the analysis of the study. We compared all ofthese variables before and after sacubitril–valsartantreatment.All patients provided informed consent, and the protocolwas approved by the research ethics committee in accor-dance with the principles of the Declaration of Helsinki andnational regulations.Statistical analysisNormally distributed continuous variables are reported asmeans with standard deviations and non-normally distributedcontinuous variables as medians. Categorical variables aresummarized as frequencies and percentages and were com-pared using χ2. We analysed before and after group differ-ences using Student’s t-test for continuous variables and χ2test for categorical values. We considered a P-value < 0.05to be statistically significant. We performed all analyses withSTATA, Version 12.0 (Texas).ResultsBetween September 2016 and March 2018, 65 patients withHFrEF (left ventricular ejection fraction mean was 37%) se-verely symptomatic were initiated to sacubitril–valsartantreatment and were followed up by the Chronic-Multimorbidity Unit. The mean age was 78.6 ± 7.4 years,and 68% of the patients were male. The median Charlsonco-morbidity index was 8 points. Chronic kidney diseasewas the most common co-morbidity (86%), presenting in58% of patients with moderate/severe kidney disease. Themost common aetiology of HFrEF was ischaemia (52%);66% of the patients received previous treatment withangiotensin-converting enzyme inhibitor or angiotensin re-ceptor blocker, and 98% received diuretic treatment. Pa-tients’ basal characteristics are described in Table 1.Treatment with sacubitril–valsartan was well toleratedwithout side effects. The mean treatment time was 286 days.Seventy-five per cent of patients received the maximum doseof 24/26 mg every 12 h.There was a significant difference of 55.68 m or more inthe 6MWT after initiating sacubitril–valsartan (223.44 vs.279.12, P < 0.001, 95% CI 74.26–27.07) (Table 2).Prior to the start of the drug treatment, most of the pa-tients had NYHA IV (74%), followed by NYHA III (25%); atthe end of the study, an improvement of NYHA was observed,being most frequently NYHA II and III (51% and 40%,P = 0.002) (Table 2).There were no statistically significant differences betweenthe mean values of the MAGGIC score (38.14 vs. 28.75). Pa-tients were classified according to the six risk groups of theTable 1 Baseline characteristics of patients prior to the start ofsacubitril–valsartanCharacteristicsa n = 65Age, years 78.6 ± 7.4Sex (M/F) 44/21BMI (kg/m2) 29.4 ± 5.6Mortality, n (%) 13 (20)Charlson co-morbidity index 8Barthel index 80Clinical features of heart failureLeft ventricular ejection fraction (%, SD) 37 ± 2.3Pulmonary blood pressure (mmHg) 46.1 ± 16.1Aetiology of heart failure, n (%)Hypertensive 14 (22)Ischaemic 34 (52)Valvular 8 (12)Mix of ischaemic/valvular 9 (14)Medical history, n (%)Hypertension 39 (65)Diabetes 44 (68)Atrial fibrillation 46 (71)Myocardial infarction 34 (52)COPD 21 (32)Chronic kidney disease, n (%) 56 (86)Stage 2 8 (12)Stage 3a 19 (29)Stage 3b 21 (32)Stage 4 17 (26)Treatment, n (%)Pre-use ACE-I or ARB 43 (66)Beta-blocker 48 (74)Mineralocorticoid agonist 28 (43)Diuretic 61 (98)Digitalis 18 (28)ACE-I, angiotensin-converting enzyme inhibitor; ARB, angiotensinreceptor blocker; BMI, body mass index; COPD, chronic obstructivepulmonary disease; IQR, inter-quartile range.aPlus–minus values are means ± SD.958 R. Rodil Fraile et al.ESC Heart Failure 2018; 5: 957–960DOI: 10.1002/ehf2.12338 20555822, 2018, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/ehf2.12338 by Universidad de Navarra, Wiley Online Library on [19/11/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons LicenseMAGGIC score. Prior to the treatment, 61% of patients werein Group 6 risk, followed by 20% in Group 5. After sacubitril–valsartan treatment, we observed a redistribution of patientsbetween Groups 3, 4, 5, and 6 (14%, 26%, 25%, and 28%, re-spectively; P < 0.001) (Table 2).On the analytical values, we found statistically signifi-cant differences in troponin level reduction (45.07 vs.36.22, P = 0.03). There were no statistically significant dif-ferences between creatinine, albumin, and HbA1c levels.There were also no differences between blood pressurelevels (Table 2).DiscussionIn our population, sacubitril–valsartan is a major break-through in HF treatment because it has shown benefit onfunctionality and risk reduction in patients with HFrEF in ad-vanced functional class and multimorbidity.The implication of different mechanisms of sacubitril–valsartan in the improvement of exercise capacity has beenpostulated (effect of natriuretic peptides, inhibition ofneprilysin, modulation of endorphin–enkephalin system),but the effect of the same remains unclear yet.In recent stud-ies, sacubitril–valsartan improves the functionality of patientsthrough the improvement of domestic activities.7 Similarstudies show an improvement in the distance travelled inthe 6MWT.6 However, the main difference in these studiesis that up to 50% of patients had advanced functional class(NYHA III/IV), unlike in our population, in which our entirestudy population presented with an advanced functionalclass. Moreover, 75% of patients only reached the maximumdose of 24/26 mg every 12 h, similar to the results found inthe literature.6It is interesting to note that the clinical benefit ob-served in our population despite age, concordant withsacubitril–valsartan, when compared with enalapril, in thestudy PARADIGM-HF, was consistent in patients >75 years.8In our population, we have observed a decrease in theMAGGIC score after the start of the drug, which is equivalentto a decrease in the risk of cardiovascular death, as wasshown in the PARADIGM-HF study regarding patients ontreatment with enalapril.9Having no control group and the limited number of pa-tients can be some of the limitations of this study.Sacubitril–valsartan, in real life, can help in the correct man-agement of patients with HFrEF and co-morbidity, even in ad-vanced stages of the disease, as well as improve thefunctionality and therefore the quality of life of our patients,also improving the prognosis, not simply with the goal of in-creasing the longevity of patients.Conflict of interestNone declared.Table 2 Comparison of the analytical and clinical characteristics before and after the start of sacubitril–valsartanCharacteristicsa Before After PClinicalBlood pressure (mmHg) 125.8 ± 18.8 127.7 ± 21.7 0.436 min walking test (m) 223.44 ± 93.55 279.12 ± 104.81 <0.001NYHA scale, n (%) 0.002Class II 1 (1) 33 (51)Class III 16 (25) 26 (40)Class IV 48 (74) 6 (9)MAGGIC score, n (%) 38.14 28.75 <0.001MAGGIC score Risk Group 1 1 (1) 2 (3)MAGGIC score Risk Group 2 1 (1) 3 (4)MAGGIC score Risk Group 3 1 (1) 9 (14)MAGGIC score Risk Group 4 11 (16) 17 (26)MAGGIC score Risk Group 5 13 (20) 16 (25)MAGGIC score Risk Group 6 38 (61) 18 (28)Treatment (mg/dL)Mineralocorticoid agonist 29.01 26.34Diuretic 78.77 96.62AnalyticsSerum creatinine (mg/dL) 1.62 ± 0.58 1.66 ± 0.58 0.53Serum troponin T (pg/mL) 45.07 ± 48.17 36.22 ± 30.45 0.03Serum HbA1c (%) 7.18 ± 1.7 7.04 ± 1.6 0.83Serum albumin (mg/dL) 3.89 ± 0.43 3.87 ± 0.36 0.44Serum BNP (pg/mL) 565.5 ± 579.49 654.21 ± 1292.2 0.36BNP, brain natriuretic peptide.aPlus–minus values are means ± SD.Sacubitril–valsartan in HF 959ESC Heart Failure 2018; 5: 957–960DOI: 10.1002/ehf2.12338 20555822, 2018, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/ehf2.12338 by Universidad de Navarra, Wiley Online Library on [19/11/2022]. 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Rodil Fraile et al.ESC Heart Failure 2018; 5: 957–960DOI: 10.1002/ehf2.12338 20555822, 2018, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/ehf2.12338 by Universidad de Navarra, Wiley Online Library on [19/11/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License

Sacubitril-valsartan in heart failure and multimorbidity patients

https://dadun.unav.edu/bitstream/10171/64849/1/ESC%20Heart%20Failure%20-%202018%20-%20Rodil%20Fraile%20-%20Sacubitril%20valsartan%20in%20heart%20failure%20and%20multimorbidity%20patients.pdf

Sacubitril-valsartan in heart failure and multimorbidity patients

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