Patients with CKD have a higher incidence of cardiovascular (acute and chronic) events, which in turn have an increased risk of progression to ESRD. Worsening renal function affects 25% of hospitalized heart failure (HF) patients and is a strong independent predictor of in-hospital as well as 1-year mortality. Hence, neurohormonal activation, including both the RAAS and sympathetic nervous system (SNS), has become the hallmark of the management of HF and CKD.

More recently, neprilysin inhibition (NEPi) has emerged as a new therapeutic strategy with potential to improve outcomes in patients with CKD. NEPi enhances the activity of natriuretic peptide systems leading to natriuresis, diuresis and inhibition of the RAS, which could act as a potentially beneficial counter-regulatory system in states of RAS activation, such as chronic HF and CKD. One such drug, LCZ696 (Sacubitril-valsartan), has shown substantial benefits in trials in hypertension and HF.

HF is common due to a range of mechanisms including hypertension and structural heart disease (including left ventricular hypertrophy), suggesting that angiotensin receptor neprilysin inhibitor (ARNi) could benefit patients with CKD by both retarding the progression of CKD (hence delaying the need for renal replacement therapy) and reducing the risk of CVD. In a new post hoc analysis of the pivotal phase III heart failure study, PARADIGM-HF, treatment with sacubitril-valsartan helped to preserve kidney function, as assessed by estimated glomerular filtration rate (eGFR), in patients with HF with reduced ejection fraction (HFrEF).

HFrEF patients treated with sacubitril-valsartan had a slower rate of decline in eGFR than those treated with ACE inhibitor enalapril. In a subgroup of patients who had both HFrEF and diabetes, the magnitude of benefit was twice as high. Earlier, the primary data from PARADIGM-HF, the largest clinical trial ever conducted in HF, showed that treatment with ARNi reduced the risk of dying from a CV cause by 20%, reduced HF hospitalizations by 21% and reduced the risk of dying from any cause by 16%, as compared to enalapril.

This new analysis adds to the growing evidence that ARNi has important clinical benefits for HF patients beyond improving their CV outcomes and hence, an effort should be made so that cardio-renal patients tolerate the new treatment.