Hospitalization and Mortality in Patients With Heart Failure Treated With Sacubitril/Valsartan vs. Enalapril: A Real-World, Population-Based Study

Abstract

Background: The effect of sacubitril/valsartan on survival and hospitalization risk in older patients with heart failure has not been explored. We aimed to investigate the risk of hospitalization and mortality with the use of sacubitril/valsartan vs. enalapril in patients with heart failure.Methods: This was a population-based cohort study using the Hong Kong-wide electronic healthcare database. Patients diagnosed with heart failure and newly prescribed sacubitril/valsartan or enalapril between July 2016 and June 2019 were included. The risk of primary composite outcome of cardiovascular mortality or heart failure-related hospitalization, all-cause hospitalization, heart failure-related hospitalization, cardiovascular mortality and all-cause mortality were compared using Cox regression with inverse probability treatment weighting. Additional analysis was conducted by age stratification.Results: Of the 44,503 patients who received sacubitril/valsartan or enalapril, 3,237 new users (sacubitril/valsartan, n = 1,056; enalapril, n = 2,181) with a diagnosis of heart failure were identified. Compared with enalapril, sacubitril/valsartan users were associated with a lower risk of primary composite outcome [hazard ratio (HR) 0.58; 95% confidence interval (CI), 0.45–0.75], heart failure-related hospitalization (HR 0.59; 95% CI, 0.45–0.77), all-cause mortality (HR 0.51; 95% CI, 0.36–0.74) and borderline non-significant reductions in all-cause hospitalization (HR 0.85; 95% CI, 0.70–1.04) and cardiovascular mortality (HR 0.63; 95% CI, 0.39–1.02). The treatment effect of sacubitril/valsartan remains unaltered in the patient subgroup age ≥ 65 years (73%).Conclusions: In real-world settings, sacubitril/valsartan was associated with improved survival and reduced heart failure-related hospitalization compared to enalapril in Asian patients with heart failure. The effectiveness remains consistent in the older population.

Sacubitril/valsartan in real‐life European patients with heart failure and reduced ejection fraction: a systematic review and meta‐analysis

“…Age was reported by all the articles on sacubitril‐valsartan prescription in Europe, and it was significantly higher than in PARADIGM‐HF. Similarly, subjects with HFrEF initiated on sacubitril‐valsartan the USA 32 , 33 and Asia 44 were older than those recruited in PARADIGM‐HF.…”

Heart Failure With Midrange Ejection Fraction: Prior Left Ventricular Ejection Fraction and Prognosis

“…Heart failure (HF) represents the final common pathway of different cardiac diseases and is a major cause of death among the elderly in many countries (1)(2)(3)(4). Currently, risk management and treatment of HF mainly depend on current left ventricular ejection fraction (LVEF) in clinical practice (5,6). In the latest European Society of Cardiology (ESC) guideline, HF was divided into HF with reduced ejection fraction (HFrEF), HF with mid-range ejection fraction (HFmrEF), and HF with preserved ejection fraction (HFpEF) based on LVEF (7).…”

Angiotensin receptor blocker neprilysin inhibitors

“…Compared to enalapril, SAC/VAL leads to reductions in symptoms of HF, cardiovascular death or HF hospitalization, sudden cardiac death, and disease progression, and improved QOL, in patients undergoing evidence-based contemporary medical therapy for HFrEF, and the NP assays for B-type NP (BNP) and N-terminal-proBNP (NT-proBNP) assays have been shown to have similar diagnostic accuracy for the differentiation of HF from other etiologies of shortness of breath[ 11 , 17 , 32 , 34 - 36 ]. In real-world settings, SAC/VAL was found to be associated with improved survival and reduced HF-related hospitalization compared to enalapril in Asian HF patients, with consistent effectiveness even in older populations[ 37 ]. SAC/VAL use has been shown to result in a modest, chronic elevation of BNP while reducing levels of NT-prBNP[ 35 ].…”

“…In the 2014 PARADIGM-HF (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial of 8399 outpatient subjects with HFrEF, SAC/VAL was found to be more effective than enalapril for slowing disease progression by decreasing the risk of worsening HF leading to the need for hospitalization or emergency admission and the need for intensified therapy; it also reduced the rates of 30-day HF readmission, as well as all-cause readmission after HF hospitalization, HF devices, or cardiac transplantation[ 24 , 31 , 37 ]. In addition, treatment with SAC/VAL was associated with statistically important reductions in cardiovascular death, a 16% reduction in all-cause mortality, and a 20% reduction in the composite of cardiovascular-related death or HF-related hospitalization (composite primary endpoint) compared to treatment with enalapril[ 16 , 26 , 33 , 37 , 47 , 48 , 50 - 52 ].…”

“…Accordingly, in 2016, the European and American cardiology societies (ACC/ AHA/Heart Failure Society of America) simultaneously issued a class I recommendation to replace ACEI with SAC/VAL for management of patients with HFrEF NYHA II-IV[ 4 , 16 , 26 , 33 , 48 , 50 , 52 ]. The results indicate that SAC/VAL should be started from the earliest symptomatic stages of the disease[ 31 , 37 ]. However, more, longer-term trials may be necessary in order to conclusively compare the efficacy of the two drugs, as well as their safety; though this is beyond the scope of this review, it is nevertheless in crucial need of evaluation[ 4 ].…”