Potential beneficial effects of sacubitril-valsartan in renal disease: a new field for a new drug

ABSTRACT

Introduction: Patients with renal dysfunction are at a higher risk of cardiovascular disease (CVD), which often shares manifestations with heart failure (HF). Last year, the FDA approved the use of sacubitril-valsartan in patients with HF. This dual-acting agent enhances the functions of natriuretic peptides and inhibits the renin-angiotensin system.

Areas covered: This review summarizes the existing preclinical and clinical studies carried out with sacubitril-valsartan (and other drugs with similar pharmacological mechanisms) in HF and hypertensive patients. We put the focus on the renal data provided by these studies. Data were obtained from English peer-reviewed articles on PubMed and clinical trials registered in ClinicalTrials.gov.

Expert opinion: Overall, sacubitril-valsartan might be a promising therapeutic approach in patients with renal dysfunction. Renal conditions with marked CV risk, such as arterionephrosclerosis, could constitute a particular setting where to evaluate the impact of the drug. Nevertheless, large, randomized trials are needed to confirm the beneficial effects and safety profile of the drug in renal patients, as well as to elucidate some concerns observed in HF trials, such as the slight increase in proteinuria.

KEYWORDS:

• Sacubitril
• valsartan
• LCZ696
• renal disease
• heart failure

Article highlights box

• Patients with renal impairment often present cardiovascular diseases that share manifestations with those found in heart failure patients.

• Sacubitril-valsartan is a new dual-acting drug developed for the treatment of heart failure, whose mechanism involves the enhancement of natriuretic peptides functions and the inhibition of the renin-angiotensin system.

• Preclinical and clinical studies in patients with heart failure and hypertension have indirectly shown that sacubitril-valsartan may have a beneficial impact on renal function.

• Clinical trials with primary renal endpoints in patients diagnosed with renal disease are needed to confirm this hypothesis.

• The results of the first of these trials (HARP III) will soon be published.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This work has been supported by Instituto de Salud Carlos III, Madrid, Spain (Pl15/00804); the Association for the Study and Prevention of Renal Diseases (ASEPER), Badajoz, Spain; and by the Junta de Extremeadura, Consejeria de Economia, Commercio e Innovacion, Merida, Spain (GR15012).