The PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) study is the key randomised-controlled trial that underpins the clinical use of sacubitril/valsartan, which demonstrated significantly improved clinical outcomes in patients with HFrEF, in comparison with angiotensin-converting enzyme (ACE) inhibition.1 Patients with HFrEF in the routine-care setting represent a clinically heterogeneous population, with a high incidence of comorbidities. Our first article dives deep into the PARADIGM-HF data, and presents the results of key subgroup analyses that support the use of sacubitril/valsartan in a broad range of patients with HFrEF.
We then present two papers from Hampshire (Portsmouth Hospitals) and Warwickshire (University Hospital Coventry and Warwickshire) looking at real-world experience of initiating sacubitril/valsartan for patients with HFrEF in major teaching hospitals. Following PARADIGM-HF, these two papers describing real-world experiences show that successful initiation and maintenance treatment with sacubitril/valsartan is feasible in clinics led by specialist HF nurse prescribers in the routine-care setting.
Any evidence-based treatment can only transform patients’ lives if it is prescribed correctly. Two more papers, from Kent (Medway Community Healthcare) and Northern Ireland (Dungannon, Co. Down) illustrate the benefits for patients and healthcare practitioners of embedding protocols and guideline-driven local guidance throughout the multi-disciplinary heart failure care team. This approach should extend to other key stakeholders, such as the hospital pharmacists. Effective communication between these stakeholders was an important factor in supporting patients to remain on sacubitril/valsartan treatment.
Together, these articles provide examples of an evidence-based and pragmatic framework for initiating and maintaining sacubitril/valsartan treatment successfully into the care of people with HFrEF, in a manner consistent with current guidelines. On behalf of all of our authors, we hope you find it interesting and useful in your own clinical practice.
Conflicts of interest
PSJ and JJVM are employees of the University of Glasgow, and the University of Glasgow has been funded by Novartis for their participation in a number of trials (including PARADIGM-HF), lectures, advisory boards, and other meetings related to sacubitril/valsartan.
Pardeep S Jhund
Clinical Senior Lecturer
John J V McMurray
Professor of Medical Cardiology
British Heart Foundation Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, 126 University Place, Glasgow, G12 8TA
1. McMurray JJV, Packer M, Desai AS et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med 2014;371:993–1004. https://doi.org/10.1056/NEJMoa1409077
Articles in this supplement
1. Applying PARADIGM-HF to the use of sacubitril/valsartan in clinical practice
2. Early clinical experience with sacubitril/valsartan from a large UK tertiary centre
3. Initial experience of introducing sacubitril/valsartan in a UK heart failure service
4. Sacubitril/valsartan prescribing and community experience in Medway
5. Real-world experience and clinical data with sacubitril/valsartan: a Northern Ireland perspective
Dosing of sacubitril/valsartan: Throughout this supplement, the dosing of sacubitril/valsartan (Entresto™▼, Novartis Pharmaceuticals) has been split to show the constituent doses.
In clinical trials, sacubitril/valsartan – initially known as the investigational agent LCZ696 – was used in 100 mg and 200 mg doses. These translate to the licensed doses of 49 mg sacubitril/51 mg valsartan and 97 mg sacubitril/103 mg of valsartan, respectively.
A smaller 50 mg dose, which equates to 24 mg sacubitril/26 mg valsartan, is also available.