Sacubitril/Valsartan Therapy in Patients with Chronic Kidney Disease and Heart Failure

Introduction to Sacubitril/Valsartan

The European Society of Cardiology recommends sacubitril/valsartan as a replacement for ACE-I or ARB in patients with heart failure with reduced ejection fraction (HFrEF) to reduce the risk of hospitalization for heart failure and death 1
The American Heart Association recommends sacubitril/valsartan for patients with chronic coronary syndrome and heart failure to reduce the risk of cardiovascular death and hospitalization 2

The American College of Cardiology recommends a blood pressure target of <130/80 mmHg (or <140/80 mmHg in elderly patients) for patients with CKD, with RAS inhibitors as first-line treatment 2
Sacubitril/valsartan can be used as an alternative to ACE inhibitors or ARB in patients with hypertension and heart failure, including those with CKD 2

The initial dose of sacubitril/valsartan should be reduced to 24/26 mg twice daily in patients with severe renal impairment, including those on hemodialysis 3
Dose titration should be done every 2-4 weeks, with a target dose of 97/103 mg twice daily, although this target may not be achievable in all hemodialysis patients 3

Patients on hemodialysis should be monitored closely for hypotension, hyperkalemia, and worsening renal function 2
The dose of sacubitril/valsartan should be adjusted based on blood pressure, potassium levels, and tolerance 3
Patients should be evaluated for signs of angioedema, and the medication should be discontinued immediately if angioedema occurs 3

Sacubitril/valsartan should not be discontinued solely due to asymptomatic hypotension, as the mortality benefits remain even with lower blood pressure 3
The medication should not be avoided solely due to the patient being on hemodialysis, as evidence shows safety and stability of renal function in CKD stages III-V 3
A 36-hour washout period from ACE inhibitors is recommended to avoid the risk of angioedema 3
The target dose of sacubitril/valsartan may not need to be achieved in all patients, as submaximal doses can still provide significant clinical benefits 3
Interactions with statins (such as atorvastatin and rosuvastatin) should be considered, and lower doses of statins may be necessary due to sacubitril's inhibition of transporters OATP1B1, OATP1B3, OAT1, and OAT3 3, 4