Application of Angiotensin Receptor–Neprilysin Inhibitor in Chronic Kidney Disease Patients: Chinese Expert Consensus

Abstract

Chronic kidney disease (CKD) is a global public health problem, and cardiovascular disease is the most common cause of death in patients with CKD. The incidence and prevalence of cardiovascular events during the early stages of CKD increases significantly with a decline in renal function. More than 50% of dialysis patients die from cardiovascular disease, including coronary heart disease, heart failure, arrhythmia, and sudden cardiac death. Therefore, developing effective methods to control risk factors and improve prognosis is the primary focus during the diagnosis and treatment of CKD. For example, the SPRINT study demonstrated that CKD drugs are effective in reducing cardiovascular and cerebrovascular events by controlling blood pressure. Uncontrolled blood pressure not only increases the risk of these events but also accelerates the progression of CKD. A co-crystal complex of sacubitril, which is a neprilysin inhibitor, and valsartan, which is an angiotensin receptor blockade, has the potential to be widely used against CKD. Sacubitril inhibits neprilysin, which further reduces the degradation of natriuretic peptides and enhances the beneficial effects of the natriuretic peptide system. In contrast, valsartan alone can block the angiotensin II-1 (AT1) receptor and therefore inhibit the renin–angiotensin–aldosterone system. These two components can act synergistically to relax blood vessels, prevent and reverse cardiovascular remodeling, and promote natriuresis. Recent studies have repeatedly confirmed that the first and so far the only angiotensin receptor–neprilysin inhibitor (ARNI) sacubitril/valsartan can reduce blood pressure more effectively than renin–angiotensin system inhibitors and improve the prognosis of heart failure in patients with CKD. Here, we propose clinical recommendations based on an expert consensus to guide ARNI-based therapeutics and reduce the occurrence of cardiovascular events in patients with CKD.

Effect of sacubitril valsartan on heart failure with mid-range or preserved ejection fraction in patients on maintenance hemodialysis: real-world experience in a single-center, prospective study

“…There is clinical evidence of the usefulness of SV for the treatment of hypertension and the delay of residual renal function loss in patients with chronic kidney disease and reduction of HF hospitalizations and cardiovascular disease-related mortality rates in patients with HFrEF [ 7 – 9 , 22 ]. For non-end-stage renal disease patients, the target dose of SV is 400 mg per day administered as 200 mg twice daily.…”

“…For non-end-stage renal disease patients, the target dose of SV is 400 mg per day administered as 200 mg twice daily. However, the target dose for dialysis patients was 100 mg twice daily in most studies [ 9 , 22 , 23 ]. Considering that SV could not be cleared by dialysis [ 24 ], the dose range of SV for patients receiving MHD in this study was 50–200 mg/day.…”

Efficacy and safety of sacubitril/valsartan after switching from azilsartan in hemodialysis patients with hypertension

“…This study was not randomized or blinded; however, the outcome of sacubitril/valsartan were not included, but it seemed to be both safe and effective for the treatment of heart failure in hemodialysis patients. 14,15 A recent Chinese consensus stated that a dose of sacubitril/valsartan of 100-150 mg daily is safe and tolerable for hemodialysis patients, 16 but further investigation is required as to the maximum dose of sacubitril/valsartan available in hemodialysis patients. The study included a limited number of patients and was conducted over a relatively short time, because sacubitril/valsartan use in hemodialysis patients was still off label in Japan, although ethics committee approval and patients' informed consent were obtained.…”

Advancing Guideline-Directed Medical Therapy in Heart Failure: Overcoming Challenges and Maximizing Benefits

“…If the serum creatinine level exceeds 30% of the baseline level, the dose of ARNIs should be promptly reduced or discontinued, and the cause should be identified. If the serum creatinine level exceeds 50% of the baseline level, the ARNI should be discontinued [ 61 ]. In patients with HF with nonsevere renal impairment, early and aggressive use of β-blockers, MRAs, and SGLT2is is recommended [ 4 ].…”