Real-world effectiveness and safety of sacubitril/valsartan in heart failure: A systematic review

Clare Proudfoot,Rachel Studer,Tanvi Rajput,Ramandeep Jindal,Rumjhum Agrawal,Stefano Corda,Michele Senni

doi:10.1016/j.ijcard.2021.01.061

Abstract

Background:PARADIGM-HF demonstrated superiority of sacubitril/valsartan (sac/val) over enalapril in patients with heart failure with reduced ejection fraction (HFrEF). However, patients in clinical practice may differ in their characteristics and overall risk compared with patients in clinical trials, and additional outcomes can be observed in real world (RW). Hence, a systematic review was conducted to identify and describe RW data on sac/val.Methods:RW studies evaluating the effects of sac/val in adult patients with HFrEF with a sample size ≥100 were identified via MEDLINE® and Embase® from 2015 to January 2020. Citations were screened, critically appraised and relevant data were extracted.Results:A total of 68 unique studies were identified. Nearly half of the studies were conducted in Europe (n = 34), followed by the US (n = 15) and Asia (n = 11). Median follow-up period varied from 1 to 19 months. Mean age ranged between 48.7 and 79.0 years; patients were mostly male and in New York Heart Association (NYHA) functional class II/III, and mean left ventricular ejection fraction varied between 23%and 38%. Of studies performing comparisons, most reported superior efficacy of sac/val in reducing the risk of HF hospitalisations, all-cause hospitalisations, and all-cause mortality as compared to standard-of-care. Many studies reported significant improvements in NYHA functional class and reduction in biomarker levels post sac/val. Hypotension and hyperkalaemia were the most frequently reported adverse events.Conclusions:This comprehensive overview of currently available RW evidence on sac/val complements the evidence from randomised controlled trials, substantiating its effectiveness in heterogeneous real-world HF populations.

Highlights

Sacubitril/valsartan is a first-in-class angiotensin receptorneprilysin inhibitor, which demonstrated superior efficacy over enalapril in reducing the risk of the composite primary endpoint of death from cardiovascular (CV) causes or heart failure (HF) hospitalisation by 20% and reducing all-cause mortality by 16% in the PARADIGM-HF trial [1]
Sac/val was recommended as a new treatment option for patients with heart failure with reduced ejection fraction (HFrEF) in the 2016 European Society for Cardiology guidelines (ESC) [2] and the 2016 American College of Cardiology/American Heart Association (ACC/AHA) guidelines [3] and more recent consensus statements reflect additional evidence from studies in patients with acute decompensated heart failure [4,5]
The main search terms included disease keywords (‘heart failure’, ‘congestive cardiomyopathy’, ‘cardiac failure’, ‘cardiac insufficiency’), treatment (‘sacubitril/valsartan’, ‘lcz696’) and keywords for real-word studies

Summary

Introduction

Sacubitril/valsartan (sac/val) is a first-in-class angiotensin receptorneprilysin inhibitor, which demonstrated superior efficacy over enalapril in reducing the risk of the composite primary endpoint of death from cardiovascular (CV) causes or HF hospitalisation by 20% and reducing all-cause mortality by 16% in the PARADIGM-HF trial [1]. Real-world evidence (RWE) allows longer follow-up and provides insights on effectiveness in a less controlled environment, including complexities of less close management of patients compared with a trial and potentially lower adherence rates. PARADIGM-HF demonstrated superiority of sacubitril/valsartan (sac/val) over enalapril in patients with heart failure with reduced ejection fraction (HFrEF). Patients in clinical practice may differ in their characteristics and overall risk compared with patients in clinical trials, and additional outcomes can be observed in real world (RW). Mean age ranged between 48.7 and 79.0 years; patients were mostly male and in New York Heart Association (NYHA) functional class II/III, and mean left ventricular ejection fraction varied between 23%and 38%. Most reported superior efficacy of sac/val in reducing the risk of HF hospitalisations, allcause hospitalisations, and all-cause mortality as compared to standard-of-care. Conclusions: This comprehensive overview of currently available RW evidence on sac/val complements the evidence from randomised controlled trials, substantiating its effectiveness in heterogeneous real-world HF populations

Results

Discussion

Conclusion