Introduction:
Patients with chronic kidney disease (CKD) are at increased risk of both progression to end-stage renal disease and cardiovascular events compared with patients with normal kidney function. Randomized controlled trials have shown that renin-angiotensin system (RAS) inhibitors slow the progression of diabetic and nondiabetic proteinuric CKD, and lowering low-density lipoprotein cholesterol reduces the risk of atherosclerotic vascular events. However, despite such treatments, a significant risk of progression to end-stage renal disease and cardiovascular events remains. In particular, patients with CKD are at increased risk of events related to structural heart disease (such as heart failure and arrhythmias), with many dying of cardiovascular disease before they reach end-stage renal disease.Natriuretic peptides have a range of potentially beneficial effects, including natriuresis, diuresis, vasodilatation, and inhibition of RAS. Neprilysin (NEP or neutral endopeptidase) is the key enzyme responsible for degrading natriuretic peptides and other vasoactive peptides, such as angiotensin II, bradykinin, endothelin, and substance P. Although inhibition of NEP (NEPi) raises concentrations of circulating natriuretic peptides, it also leads to reflex RAS activation and inhibits angiotensin II breakdown, counteracting any potentially beneficial effects, so NEPi must be combined with RAS inhibition. So the chosen method of RAS inhibition for use with NEPi is an angiotensin receptor blocker. Sacubitril/valsartan, which combines an angiotensin receptor blocker (valsartan) with a NEPi (sacubitril), was the first angiotensin receptor–neprilysin inhibitor to be developed. Several trials in populations with heart failure, including PARADIGM-HF, suggest that sacubitril/valsartan slows the decline in kidney function compared with RAS inhibition alone, but that it slightly increased albuminuria. Animal studies have shown that combining NEP and RAS inhibition can reduce proteinuria and histological evidence of kidney damage.The UK HARP-III trial (United Kingdom Heart and Renal Protection-III) aimed to compare the effects of sacubitril/valsartan versus irbesartan on kidney function and other outcomes in people with CKD. So far, no data available about the efficacy and safety of sacubitril/valsartan in ESRD patients undergoing hemodialysis, although this medication was noted to be effective and comparably well tolerable in those with estimated glomerular filtration rate(eGFR) 20 to 60 mL/min/1.73 m2 in the United Kingdom Heart and Renal Protection-III trial. The purpose of this study with prospective data collection is to assess the efficacy and safety of sacubitril/valsartan in maintenance hemodialysis patients with heart failure.
Methods:
STUDY DESIGN: Hospital based longitudinal, randomised active control prospective study. The design is based on parallel randomized controlled trials with non-inferiority.
AREA OF STUDY: The study is a single centre study conducted in the Department of Nephrology, IPGME& R and SSKM Hospital.
STUDY POPULATION: Patients diagnosed with CKD stage V on MHD having HF with reduced ejection fraction: (EF<50%)
INCLUSION CRITERIA: 1. >18 Years of age who have given written informed consent before any study assessment. 2. End stage renal disease (ESRD) patients (eGFR<15ml/min/1.73m² as measured by the Chronic Kidney Disease Epidemiology Collaboration formula at screening) who have been receiving hemodialysis 3 times a week. 3. Chronic heart failure (NYHA class ≥ II) with reduced ejection fraction, defined as known LVEF ≤ 50%. 4. Mean sitting systolic blood pressure (msSBP) ≥ 110 mmHg. 5. Good compliance.
EXCLUSION CRITERIA: 1. Acute Kidney Injury (AKI) on Renal Replacement Therapy (RRT). 2. Isolated right heart failure owing to pulmonary disease, primary cause of dyspnoea due to noncardiac, non-HF causes such as acute or chronic respiratory disorders. 3. Systolic blood pressure lower than 100 mmHg at screen 4. Previous history of intolerance or hypersensitivity to recommended target doses of angiotensin receptor blockers/ARNI. 5. Significant laboratory abnormalities at screening interfering with assessment of study drug safety or efficacy (such as serum potassium>5.5mmol/L, or alanine aminotransferase or aspartate aminotransferase>2 times the upper limit of the normal range) 6. History of angioedema. 7. Any medications that have potential for drug-drug interaction with LCZ696 /ARB will not be allowed during the study. 8. Pregnant female. 9. <18 yrs of age.
SAMPLE SIZE: About 86 known cases of CKD stage V (KDIGO 2012 Classification) on Maintenance Hemodialysis (CKDVD), who are being classified as suffering from chronic Heart Failure (NYHA Class ≥II), attending our Nephrology OPD or being admitted in ward, will be part of our study. The sample size of 86, 43 in each arm is sufficient to detect clinically important difference between two groups with error probability at 0.05 and power at 0.95. The sample size was determined using the repeated measures ANOVA in GPower.
STUDY DURATION: 1 year (AUGUST 2023- JULY 2024)
Results:
AN INTERIM ANALYSIS HAS BEEN DONE FOR THE COMPILED DATA. OUT OF TOTAL 86 PATIENTS,IN THE ARNI GROUP (SACUBITRIL-VALSARTAN) n=43, 5 patients had episodes of hyperkalemia (11.62%), while in telmisartan group N=43, 9 patients had hyperkalemia (20.9%). in the ARNI group 34 patients had NYHA class improvement (79.06%) and in the TELMISARTAN group 26 patients had NYHA improvement. in the ARNI group 36 patients had improvement in EJECTION FRACTION from baseline (83%), while 28 patients (65%) had improvement from baseline in the TELMISARTAN group. 3 patients had episodes of hypotension in in the ARNI group and 2 patients in the TELMISARTAN group. 3 patients reported of FISTULA failure in the ARNI group. and 2 with fistula failure in the TELMISARTAN group.
3 patients had episodes of hospitalisation with 1 patient expired in the ARNI group. while 2 patients had hospitalisation with 1 patient expired in the TELMISARTAN group.
Conclusions:
Our study has shown that SACUBITRIL- VALSARTAN is relatively safe in Ckd populations particularly those who are undergoing maintenance hemodialysis. it is particularly effective in improving quality of life as shown by nyha class improvement, ejection fraction imoprovement and also effective in reducing mortality. sacubitril/valsartan might reduce the risk of cardiovascular events (and in particular those related to HF) among patients with CKD.
I have no potential conflict of interest to disclose.
I did not use generative AI and AI-assisted technologies in the writing process.