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Focused Treatment of Heart Failure with Reduced Ejection Fraction Using Sacubitril/Valsartan.

ABSTRACT: The clinical syndrome of heart failure (HF) can be described as the reduced capacity of the heart to deliver blood throughout the body. To compensate for inadequate tissue perfusion, the renin-angiotensin aldosterone system (RAAS) and the sympathetic nervous system (SNS) become activated, resulting in increased blood pressure, heart rate, and blood volume. Consequent activation of the natriuretic peptide system (NPS) typically balances these effects; however, the NPS is unable to sustain compensation for excessive neurohormonal activation over time. Until recently, mortality benefits have been provided to patients with HF only by therapies that target the RAAS and SNS, including angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), mineralocorticoid receptor antagonists, and beta-blockers. Sacubitril/valsartan, the first-in-class angiotensin receptor/neprilysin inhibitor (ARNI), targets both the NPS and RAAS to further improve clinical outcomes. This review discusses the focused management of patients with HF with reduced ejection fraction (HFrEF) and suggests changes to current management paradigms. From this assessment, the evidence supports favoring sacubitril/valsartan over ACEIs or ARBs, and this therapy should be used in conjunction with beta-blockers to further decrease morbidity and mortality in patients with HFrEF.

SUBMITTER: Liu RC

PROVIDER: S-EPMC6267534 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Focused Treatment of Heart Failure with Reduced Ejection Fraction Using Sacubitril/Valsartan.

Liu Rex C RC

American journal of cardiovascular drugs : drugs, devices, and other interventions 20181201 6

The clinical syndrome of heart failure (HF) can be described as the reduced capacity of the heart to deliver blood throughout the body. To compensate for inadequate tissue perfusion, the renin-angiotensin aldosterone system (RAAS) and the sympathetic nervous system (SNS) become activated, resulting in increased blood pressure, heart rate, and blood volume. Consequent activation of the natriuretic peptide system (NPS) typically balances these effects; however, the NPS is unable to sustain compens ...[more]

PMID: 29850980

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Project description:Background Sacubitril/Valsartan has been highly efficacious in randomized trials of heart failure with reduced ejection fraction (HFrEF). However, the effectiveness of sacubitril/valsartan in older patients hospitalized for HFrEF in real-world US practice is unclear. Methods and Results This study included Medicare beneficiaries age ≥65 years who were hospitalized for HFrEF ≤40% in the Get With The Guidelines-Heart Failure registry between October 2015 and December 2018, and eligible for sacubitril/valsartan. Associations between discharge prescription of sacubitril/valsartan and clinical outcomes were assessed after inverse probability of treatment weighting and adjustment for other HFrEF medications. Overall, 1551 (10.9%) patients were discharged on sacubitril/valsartan. Of those not prescribed sacubitril/valsartan, 7857 (62.0%) were prescribed an angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker. Over 12-month follow-up, compared with a discharge prescription of angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker, sacubitril/valsartan was independently associated with lower all-cause mortality (adjusted hazard ratio [HR], 0.82; 95% CI, 0.72-0.94; P=0.004) but not all-cause hospitalization (adjusted HR, 0.97; 95% CI, 0.89-1.07; P=0.55) or heart failure hospitalization (adjusted HR, 1.04; 95% CI, 0.91-1.18; P=0.59). Patients prescribed sacubitril/valsartan versus those without a prescription had lower risk of all-cause mortality (adjusted HR, 0.69; 95% CI, 0.60-0.79; P<0.001), all-cause hospitalization (adjusted HR, 0.90; 95% CI, 0.82-0.98; P=0.02), but not heart failure hospitalization (adjusted HR, 0.94; 95% CI, 0.82-1.08; P=0.40). Conclusions Among patients hospitalized for HFrEF, prescription of sacubitril/valsartan at discharge was independently associated with reduced postdischarge mortality compared with angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker, and reduced mortality and all-cause hospitalization compared with no sacubitril/valsartan. These findings support the use of sacubitril/valsartan to improve postdischarge outcomes among older patients hospitalized for HFrEF in routine US clinical practice.

Project description:AimsIvabradine and sacubitril/valsartan are second-line therapies for patients with heart failure and reduced ejection fraction (HFrEF) based on guideline recommendations. We aimed to evaluate the synergistic effects of these two medications.Methods and resultsPatients' data were extracted from a multicentre database between 2016 and 2018. Patients were classified into (1) Simultaneous group: simultaneous prescription of ivabradine and sacubitril/valsartan within 6 weeks; (2A) Sequential group, ivabradine-first: ivabradine was prescribed first, followed by sacubitril/valsartan; and (2B) Sequential group, sacubitril/valsartan-first: sacubitril/valsartan was prescribed first, followed by ivabradine. A total of 464 patients with HFrEF were enrolled. Cardiovascular death and/or unplanned re-hospitalizations for HF were less frequent (28.6% vs. 44.8%, P = 0.01), and the improvement of left ventricular ejection fraction (LVEF) was significantly greater in patients from the Simultaneous group than those from the Sequential group (∆LVEF 12.8 ± 12.9% vs. 9.3 ± 12.6%, P = 0.007). Among Sequential subgroups, the ivabradine-first treatment decreased heart rate and increased systolic blood pressure (SBP) compared with sacubitril/valsartan-first treatment (∆heart rate -9.1 ± 12.9 b.p.m. vs. 2.6 ± 16.0 b.p.m., P < 0.001; ∆SBP 4.6 ± 16.5 mmHg vs. -4.8 ± 17.2 mmHg, P < 0.001), whereas sacubitril/valsartan-first treatment showed a higher degree of LVEF improvement (∆LVEF 3.6 ± 7.8% vs. 0.7 ± 7.7%, P = 0.002) than ivabradine-first treatment. At the end of follow-up, SBP, LVEF, and left ventricular volume were comparable between two Sequential subgroups.ConclusionsAmong patients with HFrEF, simultaneous rather than sequential treatment with sacubitril/valsartan and ivabradine was a better strategy to reduce adverse events and achieve left ventricular reverse remodelling. Ivabradine treatment had a more significant benefit on improving haemodynamic stability, whereas sacubitril/valsartan treatment showed a more significant effect on improving LVEF.

Project description:ObjectivesThis paper aims to compare the effectiveness of sacubitril-valsartan and angiotensin-converting enzyme inhibitor (ACE)/angiotensin receptor blocker (ARB) in systolic heart failure (HF).BackgroundSacubitril-valsartan reduced risks of death and hospitalization for HF versus enalapril in ambulatory patients with HF and reduced ejection fraction in the PARADIGM-HF (Prospective Comparison of Angiotensin II Receptor Blocker Neprilysin Inhibitor with Angiotensin Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in HF) trial. However, the comparative effectiveness of sacubitril-valsartan and ACE/ARB in patients treated in routine clinical practice is unclear.MethodsWe identified patients with systolic HF in a U.S. administrative claims database treated with sacubitril-valsartan or ACE/ARB from July 1, 2015, to February 2, 2018. One-to-one propensity score matching was used to balance patients on 29 clinical variables. Cox models were used to compare outcomes between treatment groups.ResultsA total of 7,893 matched pairs were included; mean (SD) follow-up was 6.3 (5.4) months. Sacubitril-valsartan was associated with lower risks of all-cause mortality or all-cause hospitalization (hazard ratio [HR]: 0.86, 95% confidence interval (CI): 0.81 to 0.91; p < 0.001), all-cause mortality (HR: 0.80, 95% CI: 0.66 to 0.97; p = 0.027), and all-cause hospitalization (HR: 0.86, 95% CI: 0.80 to 0.91; p < 0.001), but not HF hospitalization (HR: 1.07, 95% CI: 0.96 to 1.19; p = 0.26). A lower risk of the primary outcome with sacubitril-valsartan was observed in white patients (HR: 0.83, 95% CI: 0.76 to 0.90) but not black patients (21% of population, HR: 1.00, 95% CI: 0.88 to 1.15; interaction p = 0.032). No statistically significant differences in treatment response by sex or age were observed.ConclusionsSacubitril-valsartan was associated with lower risks of death and hospitalization compared with ACE/ARB in a heterogeneous cohort of patients with systolic HF. However, our finding that outcomes with sacubitril-valsartan and ACE/ARBs were similar in black patients warrants further evaluation.

Project description:ObjectivesThis study sought to describe the short-term health status benefits of angiotensin-neprilysin inhibitor (ARNI) therapy in patients with heart failure and reduced ejection fraction (HFrEF).BackgroundAlthough therapy with sacubitril/valsartan, a neprilysin inhibitor, improved patients' health status (compared with enalapril) at 8 months in the PARADIGM-HF (Prospective Comparison of ARNI with ACE inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) study, the early impact of ARNI on patients' symptoms, functions, and quality of life is unknown.MethodsHealth status was assessed by using the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ) in 3,918 outpatients with HFrEF and left ventricular ejection fraction ≤40% across 140 U.S. centers in the CHAMP-HF (Change the Management of Patients with Heart Failure) registry. ARNI therapy was initiated in 508 patients who were matched 1:2 to 1,016 patients who were not initiated on ARNI (no-ARNI), using a nonparsimonious time-dependent propensity score (6 sociodemographic factors, 23 clinical characteristics), prior KCCQ overall summary (KCCQ-OS) score, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker status.ResultsMultivariate linear regression demonstrated a greater mean improvement in KCCQ-OS in patients initiated on ARNI therapy (5.3 ± 19 vs. 2.5 ± 17.4, respectively; p < 0.001) over a median (interquartile range [IQR]) of 57 (32 to 104) days. The proportions of ARNI versus no-ARNI groups with ≥10-point (large) and ≥20-point (very large) improvements in KCCQ-OS were 32.7% versus 26.9%, respectively, and 20.5% versus 12.1%, respectively, consistent with numbers needed to treat of 18 and 12, respectively.ConclusionsIn routine clinical care, ARNI therapy was associated with early improvements in health status, with 20% experiencing a very large health status benefit compared with 12% who were not started on ARNI therapy. These findings support the use of ARNI to improve patients' symptoms, functions, and quality of life.

Project description:AimsARIADNE aimed to assess the association between effects of sacubitril/valsartan and no sacubitril/valsartan treatment and clinical characteristics, functional capacity, and clinical outcomes (cause-specific mortality and hospitalizations) in outpatients with heart failure (HF) with reduced ejection fraction (HFrEF).MethodsARIADNE was a prospective European registry of 9069 patients with HFrEF treated by office-based cardiologists or selected primary care physicians. Of the 8787 eligible for analysis, 4173 patients were on conventional HF treatment (non-S/V group), whereas 4614 patients were either on sacubitril/valsartan treatment at enrolment or started sacubitril/valsartan within 1 month of enrolment (S/V group). We also generated a restricted analysis set (rS/V) including only those 2108 patients who started sacubitril/valsartan treatment within the month prior to or after enrolment.ResultsAt the baseline, average age of patients enrolled in the study was 68 years, and 23.9% (2099/8787) were female. At the baseline, the proportions of patients with New York Heart Association (NYHA) Class III symptoms were 30.9 (1288/4173), 42.8 (1974/4614), and 48.2% (1015/2108), in non-S/V, S/V, and rS/V groups, respectively. After 12 months of treatment, the proportion of patients with NYHA Class III at baseline who improved to Class II was 32.0% (290/907) in the non-S/V group vs. 46.3% (648/1399) in S/V group and 48.7% (349/717) in rS/V group. The overall mortality rate was 5.0 per 100 patient-years. Rates of HF hospitalizations were high (20.9, 20.3, and 21.2 per 100 patient-years in the non-S/V, S/V, and rS/V groups, respectively). Emergency room visits without hospitalization occurred in 3.9, 3.2, and 3.9% of patients in the non-S/V, S/V, and rS/V groups, respectively.ConclusionsThis large HFrEF European registry provides a contemporary outcome profile of outpatients with HFrEF treated with or without sacubitril/valsartan. In a real-world setting, sacubitril/valsartan was associated with an improvement of symptoms in patients with HFrEF compared with the conventional HFrEF treatment.

Dataset Information

Focused Treatment of Heart Failure with Reduced Ejection Fraction Using Sacubitril/Valsartan.

Publications

Focused Treatment of Heart Failure with Reduced Ejection Fraction Using Sacubitril/Valsartan.

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