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      Sacubitril/Valsartan in Asian Patients with Heart Failure with Reduced Ejection Fraction

      review-article
      , MBBS, MSc, , BSc, MBChB, , MD
      Korean Circulation Journal
      The Korean Society of Cardiology
      Asians, Sacubitril/valsartan, Heart failure

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          Abstract

          The Prospective comparison of Angiotensin Receptor-neprilysin inhibitor (ARNI) with Angiotensin converting enzyme inhibitor (ACEI) to Determine Impact on Global Mortality and morbidity in Heart Failure (HF) trial (PARADIGM-HF) showed that adding a neprilysin inhibitor (sacubitril) to a renin-angiotensin system blocker (and other standard therapy) reduced morbidity and mortality in ambulatory patients with chronic HF with reduced ejection fraction (HFrEF). In PARADIGM-HF, valsartan combined with sacubitril (a so-called ARNI) was superior to the current gold standard of an ACEI, specifically enalapril, reducing the risk of the primary composite outcome of cardiovascular (CV) death or first HF hospitalization by 20% and all-cause death by 16%. Following the results of PARADIGM-HF, sacubitril/valsartan was approved by American and European regulatory authorities for the treatment of HFrEF. The burden of HF in Asia is substantial, both due to the huge population of the region and as a result of increasing CV risk factors and disease. Both the prevalence and mortality associated with HF are high in Asia. In the following review, we discuss the development of sacubitril/valsartan, the prototype ARNI, and the available evidence for its efficacy and safety in Asian patients with HFrEF.

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          Most cited references49

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          Effect of Enalapril on Mortality and the Development of Heart Failure in Asymptomatic Patients with Reduced Left Ventricular Ejection Fractions

          New England Journal of Medicine, 327(10), 685-691
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            Effect of nesiritide in patients with acute decompensated heart failure.

            Nesiritide is approved in the United States for early relief of dyspnea in patients with acute heart failure. Previous meta-analyses have raised questions regarding renal toxicity and the mortality associated with this agent. We randomly assigned 7141 patients who were hospitalized with acute heart failure to receive either nesiritide or placebo for 24 to 168 hours in addition to standard care. Coprimary end points were the change in dyspnea at 6 and 24 hours, as measured on a 7-point Likert scale, and the composite end point of rehospitalization for heart failure or death within 30 days. Patients randomly assigned to nesiritide, as compared with those assigned to placebo, more frequently reported markedly or moderately improved dyspnea at 6 hours (44.5% vs. 42.1%, P=0.03) and 24 hours (68.2% vs. 66.1%, P=0.007), but the prespecified level for significance (P≤0.005 for both assessments or P≤0.0025 for either) was not met. The rate of rehospitalization for heart failure or death from any cause within 30 days was 9.4% in the nesiritide group versus 10.1% in the placebo group (absolute difference, -0.7 percentage points; 95% confidence interval [CI], -2.1 to 0.7; P=0.31). There were no significant differences in rates of death from any cause at 30 days (3.6% with nesiritide vs. 4.0% with placebo; absolute difference, -0.4 percentage points; 95% CI, -1.3 to 0.5) or rates of worsening renal function, defined by more than a 25% decrease in the estimated glomerular filtration rate (31.4% vs. 29.5%; odds ratio, 1.09; 95% CI, 0.98 to 1.21; P=0.11). Nesiritide was not associated with an increase or a decrease in the rate of death and rehospitalization and had a small, nonsignificant effect on dyspnea when used in combination with other therapies. It was not associated with a worsening of renal function, but it was associated with an increase in rates of hypotension. On the basis of these results, nesiritide cannot be recommended for routine use in the broad population of patients with acute heart failure. (Funded by Scios; ClinicalTrials.gov number, NCT00475852.).
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              Natriuretic peptides.

              Natriuretic peptides (NPs) are released from the heart in response to pressure and volume overload. B-type natriuretic peptide (BNP) and N-terminal-proBNP have become important diagnostic tools for assessing patients who present acutely with dyspnea. The NP level reflects a compilation of systolic and diastolic function as well as right ventricular and valvular function. Studies suggest that using NPs in the emergency department can reduce the consumption of hospital resources and can lower costs by either eliminating the need for other, more expensive tests or by establishing an alternative diagnosis that does not require hospital stay. Caveats such as body mass index and renal function must be taken into account when analyzing NP levels. Natriuretic peptide levels have important prognostic value in multiple clinical settings, including in patients with stable coronary artery disease and with acute coronary syndromes. In patients with decompensated heart failure due to volume overload, a treatment-induced drop in wedge pressure is often accompanied by a rapid drop in NP levels. Knowing a patient's NP levels might thus assist with hemodynamic assessment and subsequent treatment titration. Monitoring NP levels in the outpatient setting might also improve patient care and outcomes.
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                Author and article information

                Journal
                Korean Circ J
                Korean Circ J
                KCJ
                Korean Circulation Journal
                The Korean Society of Cardiology
                1738-5520
                1738-5555
                June 2019
                28 May 2019
                : 49
                : 6
                : 469-484
                Affiliations
                British Heart Foundation Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
                Author notes
                Correspondence to John J.V. McMurray, MD. British Heart Foundation Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK. john.mcmurray@ 123456glasgow.ac.uk
                Author information
                https://orcid.org/0000-0003-2927-4075
                https://orcid.org/0000-0002-5446-9969
                https://orcid.org/0000-0002-6317-3975
                Article
                10.4070/kcj.2019.0136
                6554586
                31172710
                623481e9-5387-4db7-9d71-15d04fdab63b
                Copyright © 2019. The Korean Society of Cardiology

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 06 May 2019
                : 19 May 2019
                Categories
                Review Article

                Cardiovascular Medicine
                asians,sacubitril/valsartan,heart failure
                Cardiovascular Medicine
                asians, sacubitril/valsartan, heart failure

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