Effects of Sacubitril/Valsartan on Physical and Social Activity Limitations in Patients With Heart Failure

Chandra, Alvin; Lewis, Eldrin F.; Claggett, Brian; Desai, Akshay S.; Packer, Milton; Zile, Michael R.; Swedberg, Karl; Rouleau, Jean L.; Shi, Victor; Lefkowitz, Martin; Katova, Tzvetana; McMurray, John J.V.; Solomon, Scott D.

doi:10.1001/jamacardio.2018.0398

Cited by 95 publications

(99 citation statements)

References 26 publications

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“…The implication of different mechanisms of sacubitril–valsartan in the improvement of exercise capacity has been postulated (effect of natriuretic peptides, inhibition of neprilysin, modulation of endorphin–enkephalin system), but the effect of the same remains unclear yet.In recent studies, sacubitril–valsartan improves the functionality of patients through the improvement of domestic activities . Similar studies show an improvement in the distance travelled in the 6MWT .…”

Section: Discussionmentioning

confidence: 67%

“…The PARADIGM‐HF (Prospective Comparison of ARNI with an ACE‐Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial showed that sacubitril–valsartan reduced the risk of cardiovascular death or first hospitalization for HF. But there is little evidence regarding the study of the functionality of patients after treatment, and there is little evidence of the drug in elderly patients with multimorbidity …”

Section: Introductionmentioning

confidence: 99%

“…4 The PARADIGM-HF (Prospective Comparison of ARNI with an ACE-Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial 5 showed that sacubitril-valsartan reduced the risk of cardiovascular death or first hospitalization for HF. But there is little evidence regarding the study of the functionality of patients after treatment, 6,7 and there is little evidence of the drug in elderly patients with multimorbidity. 8 The aim of this study is to evaluate if the use of sacubitrilvalsartan improves functionality in multimorbidity patients with HF and the factors and prognostic tests in elderly patients with advanced HF and multimorbidity.…”

Section: Introductionmentioning

confidence: 99%

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Sacubitril–valsartan in heart failure and multimorbidity patients

2018

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AimsThe 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 resultsFrom 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.ConclusionsSacubitril–valsartan relieves symptoms and improves functional class prognostic risk of patients with advanced HFrEF and co‐morbidity.

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Section: Discussionmentioning

confidence: 67%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Sacubitril–valsartan in heart failure and multimorbidity patients

2018

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“…ACEi or angiotensin receptor blockers (ARB), beta blockers, and mineralocorticoid antagonists (MRA) are the pillars of current management of HFrEF. 42,43 Based on these results, 40,44 sacubitril/valsartan is currently recommended as a replacement for ACEi/ARBs in ambulatory patients with HFrEF who remain symptomatic despite optimal medical treatment. 4 PARADIGM-HF trial showed a reduction in the combined endpoint of CV death or HF hospitalizations, (HR, 0.80; 95% CI, 0.73 to 0.87) as well as all-cause death, CV death and HF hospitalizations alone, and an improvement in symptoms with sacubitril/valsartan vs. enalapril.…”

Section: Neurohormonal Antagonistsmentioning

confidence: 99%

“…41 Quality of life improved and diuretic doses were slightly but significantly reduced in the patients on sacubitril/valsartan, consistent with favourable effects also on symptoms. 42,43 Based on these results, 40,44 sacubitril/valsartan is currently recommended as a replacement for ACEi/ARBs in ambulatory patients with HFrEF who remain symptomatic despite optimal medical treatment. 4, 45 Based on more recent trials, 44,46 it may be considered also in patients hospitalized for acute HF, including also those with new onset HF.…”

Section: Neurohormonal Antagonistsmentioning

confidence: 99%

Highlights in heart failure

et al. 2019

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Heart failure (HF) remains a major cause of mortality, morbidity, and poor quality of life. It is an area of active research. This article is aimed to give an update on recent advances in all aspects of this syndrome. Major changes occurred in drug treatment of HF with reduced ejection fraction (HFrEF). Sacubitril/valsartan is indicated as a substitute to ACEi/ARBs after PARADIGM-HF (hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.73 to 0.87 for sacubitril/valsartan vs. enalapril for the primary endpoint and Wei, Lin and Weissfeld HR 0.79, 95% CI 0.71-0.89 for recurrent events). Its initiation was then shown as safe and potentially useful in studies in patients hospitalized for acute HF. More recently, DAPA-HF trial showed the beneficial effects of the sodium-glucose transporter type 2 (SGLT2) inhibitor dapaglifozin vs. placebo, added to optimal standard therapy [HR, 0.74; 95% CI, 0.65 to 0.85;0.74; 95% CI, 0.65 to 0.85 for the primary endpoint]. Trials with other SGLT 2 inhibitors and in other patients, such as those with HF with preserved ejection fraction (HFpEF) or with recent decompensation, are ongoing. Multiple studies showed the unfavourable prognostic significance of abnormalities in serum potassium levels. Potassium lowering agents may allow initiation and titration of mineralocorticoid antagonists in a larger proportion of patients. Meta-analyses suggest better outcomes with ferric carboxymaltose in patients with iron deficiency. Drugs effective in HFrEF may be useful also in HF with mid-range ejection fraction. Better diagnosis and phenotype characterization seem warranted in HF with preserved ejection fraction. These and other burning aspects of HFpEF research are summarized and reviewed in this article.A multiparametric approach is often proposed for risk stratification of HF patients. The prognostic accuracy of the metabolic exercise test data combined with cardiac and kidney indexes risk score was found as superior to the HF Survival Score and Seattle HF model risk scores in a cohort of 6112 1106 D. Tomasoni et al.

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Estimated 5-Year Number Needed to Treat to Prevent Cardiovascular Death or Heart Failure Hospitalization With Angiotensin Receptor-Neprilysin Inhibition vs Standard Therapy for Patients With Heart Failure With Reduced Ejection Fraction

et al. 2018

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The addition of neprilysin inhibition to standard therapy, including a renin-angiotensin system blocker, has been demonstrated to improve outcomes in patients with heart failure with reduced ejection fraction (HFrEF) compared with standard therapy alone. The long-term absolute risk reduction from angiotensin receptor-neprilysin inhibitor (ARNI) therapy, and whether it merits widespread use among diverse subpopulations, has not been well described. OBJECTIVE To calculate estimated 5-year number needed to treat (NNT) values overall and for different subpopulations for the Prospective Comparison of ARNI with Angiotensin-Converting Enzyme Inhibitor (ACEI) to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) cohort. DESIGN, SETTING, AND PARTICIPANTS Overall and subpopulation 5-year NNT values were estimated for different end points using data from PARADIGM-HF, a double-blind, randomized trial of sacubitril-valsartan vs enalapril. This multicenter, international study included 8399 men and women with HFrEF (ejection fraction, Յ40%). The study began in December 2009 and ended in March 2014. Analyses began in March 2018. INTERVENTIONS Random assignment to sacubitril-valsartan or enalapril. MAIN OUTCOMES AND MEASURES Cardiovascular death or HF hospitalization, cardiovascular death, and all-cause mortality. RESULTS The final cohort of 8399 individuals included 1832 women (21.8%) and 5544 white individuals (66.0%), with a mean (SD) age of 63.8 (11.4) years. The 5-year estimated NNT for the primary outcome of cardiovascular death or HF hospitalization with ARNI therapy incremental to ACEI therapy in the overall cohort was 14. The 5-year estimated NNT values were calculated for different clinically relevant subpopulations and ranged from 12 to 19. The 5-year estimated NNT for all-cause mortality in the overall cohort with ARNI incremental to ACEI was 21, with values ranging from 16 to 31 among different subgroups. Compared with imputed placebo, the 5-year estimated NNT for all-cause mortality with ARNI was 11. The 5-year estimated NNT values were also calculated for other HFrEF therapies compared with controls from landmark trials for all-cause mortality and were found to be 18 for ACEI, 24 for angiotensin receptor blockers, 8 for β-blockers, 15 for mineralocorticoid antagonists, 14 for implantable cardioverter defibrillator, and 14 for cardiac resynchronization therapy. CONCLUSIONS AND RELEVANCE The 5-year estimated NNT with ARNI therapy incremental to ACEI therapy overall and for clinically relevant subpopulations of patients with HFrEF are comparable with those for well-established HF therapeutics. These data further support guideline recommendations for use of ARNI therapy among eligible patients with HFrEF.

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Effects of Sacubitril/Valsartan on Physical and Social Activity Limitations in Patients With Heart Failure

Abstract: clinicaltrials.gov Identifier: NCT01035255.

Cited by 95 publications

References 26 publications

Sacubitril–valsartan in heart failure and multimorbidity patients

Sacubitril–valsartan in heart failure and multimorbidity patients

Highlights in heart failure

Estimated 5-Year Number Needed to Treat to Prevent Cardiovascular Death or Heart Failure Hospitalization With Angiotensin Receptor-Neprilysin Inhibition vs Standard Therapy for Patients With Heart Failure With Reduced Ejection Fraction

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