sacubitril and Renal-Insufficiency--Chronic

The prevalence and mortality of heart failure with preserved ejection fraction (HFpEF) are high in patients with chronic kidney disease (CKD). However, there is still a lack of recommendations for the medication therapy of these patients in the guideline so far.. We conducted a systematic review and meta-analysis of all the studies assessing medication therapy for patients with CKD and HFpEF by July 21, 2021. Pooled analysis was performed using a random-effect model and the quality assessment was performed. In our research, we followed to the Preferred Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The meta-analysis was registered on PROSPERO.. We finally identified six studies, three of which were randomized controlled trials and the others were retrospective cohort studies. The results of meta-analysis including three retrospective cohort studies showed that renin-angiotensin system inhibitors had significantly reduced all-cause mortality by 14% (3 studies, 3816 patients, HR 0.86; 95% CI 0.79-0.95; I. For patients with CKD and HFpEF, renin-angiotensin system inhibitors is associated with significant benefits in all-cause mortality and all-cause hospitalization but has no significant effect on hospitalization for heart failure. The subgroup analysis of one RCT study focused on ARNI showed that although long-term treatment with sacubitril-valsartan may reduce the risk of hospitalization for heart failure and cardiovascular death, more studies are needed to confirm that.

Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Biphenyl Compounds; Drug Combinations; Female; Heart Failure; Humans; Male; Renal Insufficiency, Chronic; Retrospective Studies; Stroke Volume; Valsartan

While it is well known that angiotensin-converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARBs) increase the risk of acute renal failure, the role of neprilysin inhibition (NEPi) is unclear and some physicians are reluctant to prescribe sacubitril/valsartan because of safety concerns. This meta-analysis aimed to examine the risk for renal events, progression of chronic kidney disease (CKD) or progression to dialysis on combined NEPi and ACEi/ARBs compared with ACEi or ARBs.. We performed a systematic meta-analysis including 17 randomized controlled trials (study drug sacubitril/valsartan or omapatrilat), involving a total of 23 569 patients, after searching PubMed, Cochrane, ClinicalTrials.org and Embase for eligible studies. From the included trials, all renal endpoints, including long- and short-term outcomes and hyperkalemia, were extracted. Pooled odds ratios (ORs) were calculated using the DerSimonian and Laird method. The study was registered at PROSPERO.. Overall, treatment with sacubitril/valsartan or omapatrilat showed a slightly lower risk of any renal event [OR 0.82 (0.7-0.97)] compared with treatment with an ACEi or ARB alone. Also, there was a decreased risk of severe acute renal events [OR 0.8 (0.69-0.93)] and a decrease in estimated glomerular filtration rate decline [mean difference -0.58 mL/min (-0.83 to -0.33 mL/min)]. There was no difference in chronic renal events [OR 0.92 (0.8-1.05)] or hyperkalemia [OR 1.02 (0.84-1.23)].. NEPi + ACEi/ARBs are safe in terms of renal adverse events. Longer trials focusing on CKD are needed to evaluate the effect of NEPi on decreasing progression of CKD.

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Humans; Hyperkalemia; Neprilysin; Randomized Controlled Trials as Topic; Renal Dialysis; Renal Insufficiency, Chronic; Valsartan

Hypertension is a leading cause of cardiovascular disease and chronic kidney disease, resulting in premature death and disability. The Renin-Angiotensin-Aldosterone System (RAAS) blockers, including Angiotensin-Converting Enzyme (ACE) inhibitors or Angiotensin Receptor Blockers (ARBs), are used as first-line antihypertensive therapy to treat hypertensive patients with comorbidities, including diabetes, ischemic heart disease, heart failure, and chronic kidney disease. The use of RAS blockers is associated with the risks, such as hyperkalemia, angioedema, etc. The drugs potentiating them interact pharmacodynamically, resulting in adverse consequences. This review article focuses on the clinically important drug interactions of RAAS blockers.. The electronic databases, such as Medline/PubMed Central/PubMed, Google Scholar, ScienceDirect, Cochrane Library, Directory of Open Access Journals (DOAJ), Embase, and reference lists were searched to identify relevant articles.. The risk of hyperkalemia may be enhanced potentially in patients receiving a RAS blocker and potassium-sparing diuretics, potassium supplements, trimethoprim, adrenergic betablockers, antifungal agents, calcineurin inhibitors, pentamidine, heparins or an NSAID, concomitantly. The patients taking ACE inhibitors and mTOR inhibitors, DPP4 inhibitors, alteplase, or sacubitril/valsartan concurrently may be at increased risk of developing angioedema.. Clinicians, pharmacists, and other healthcare practitioners should be accountable for medication safety. To avoid adverse implications, prescribers and pharmacists must be aware of the drugs that interact with RAAS blockers.

Topics: Angioedema; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Drug Interactions; Humans; Hyperkalemia; Hypertension; Potassium; Renal Insufficiency, Chronic; Renin-Angiotensin System

The amount of evidence for guideline-directed new heart failure (HFrEF) disease-modifying drugs in the context of chronic kidney disease (CKD) is relatively modest, especially in end-stage CKD. We report a case of dramatic reverse remodelling and disease regression in a naïve HFrEF young woman on haemodialysis treated with sacubitril/valsartan and SGLT2i. At 10-month follow-up, the patient normalized left ventricle and atrial volumes and improved ejection fraction to the normal range, assessed both by echocardiography and cardiac magnetic resonance. Cardiac biomarkers and exercise performance improved consensually. The haemodialysis protocol and the loop diuretic dose were unchanged within the whole period.

Topics: Female; Heart Failure; Humans; Kidney Failure, Chronic; Renal Insufficiency, Chronic; Stroke Volume; Tetrazoles; Valsartan

There are few contemporary data on outcomes, costs, and treatment following a hospitalization for heart failure (hHF) in epidemiologically representative cohorts.. This study sought to describe rehospitalizations, hospitalization costs, use of guideline-directed medical therapy (GDMT) (renin-angiotensin system inhibitors, sacubitril/valsartan, beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter-2 inhibitors), and mortality after hHF.. EVOLUTION HF (Utilization of Dapagliflozin and Other Guideline Directed Medical Therapies in Heart Failure Patients: A Multinational Observational Study Based on Secondary Data) is an observational, longitudinal cohort study using data from electronic health records or claims data sources in Japan, Sweden, the United Kingdom, and the United States. Adults with a first hHF discharge between 2018 and 2022 were included. The 1-year event rates per 100 patient-years (ERs) for death and rehospitalizations (with a primary diagnosis of heart failure (HF), chronic kidney disease [CKD], myocardial infarction, stroke, or peripheral artery disease) were calculated. Hospital health care costs were cumulatively summarized. Cumulative GDMT use was assessed using Kaplan-Meier estimates.. Of 263,525 patients, 28% died within the first year post-hHF (ER: 28.4 [95% CI: 27.0-29.9]). Rehospitalizations were mainly driven by HF (ER: 13.6 [95% CI: 9.8-17.4]) and CKD (ER: 4.5 [95% CI: 3.6-5.3]), whereas the ERs for myocardial infarction, stroke, and peripheral artery disease were lower. Health care costs were predominantly driven by HF and CKD. Between 2020 and 2022, use of renin-angiotensin system inhibitors, sacubitril/valsartan, beta-blockers, and mineralocorticoid receptor antagonists changed little, whereas uptake of sodium-glucose cotransporter-2 inhibitors increased 2- to 7-fold.. Incident post-hHF rehospitalization risks and costs were high, and GDMT use changed little in the year following discharge, highlighting the need to consider earlier and greater implementation of GDMT to manage risks and reduce costs.

Topics: Adrenergic beta-Antagonists; Adult; Angiotensin Receptor Antagonists; Antihypertensive Agents; Glucose; Heart Failure; Hospitalization; Humans; Longitudinal Studies; Mineralocorticoid Receptor Antagonists; Myocardial Infarction; Peripheral Arterial Disease; Renal Insufficiency, Chronic; Sodium; Sodium-Glucose Transporter 2 Inhibitors; Stroke; Stroke Volume; United States; Valsartan

Patients with chronic kidney disease (CKD) are often complicated with heart failure with preserved ejection fraction (HFpEF). However, several drugs, including angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB), have not shown apparent benefits in terms of morbidity and mortality of HFpEF. PARAMOUNT and other studies have shown the potential benefits of Sacubitril/Valsartan on patients with HFpEF, but its effects on renal function and the effect of low-dose Sacubitril/Valsartan in actual clinical conditions have not been thoroughly evaluated. In our longitudinal and observational research, 353 patients were followed up for 12 weeks. We evaluated renal function [urinary protein, serum creatinine and estimated glomerular filtration rate (eGFR)] and cardiac function [NT-proBNP (brain natriuretic peptide), New York Heart Association (NYHA) classification, left ventricular ejection fraction (LVEF), left atrial width and left ventricular end-diastolic width] at baseline and during follow-up. Worsening renal function (WRF) was defined as an increased serum creatinine≥26.5umol/L or decreased eGFR≥20%. The decline of eGFR in the Sacubitril/Valsartan group was slower than that in the control group (p = 0.021). The outcome of proteinuria in the ACEI/ARB group was significantly better than that in the Sacubitril/Valsartan group (p = 0.001). In terms of echocardiogram, the average left atrial width in Sacubitril/Valsartan group decreased by 1.38 ± 3.02 mm, which was significantly lower than that in the ACEI/ARB group (p = 0.02). The increase of urine protein class in the ACEI/ARB group increased the risk of WRF with statistical significance (OR = 2.36, 95%CI 1.01-5.49, p = 0.047), but no statistical significance was found in all the patients or Sacubitril/Valsartan group. In conclusion, Sacubitril/Valsartan could more effectively slow down renal function decline and reverse myocardial remodeling in patients with CKD and HFpEF than ACEI/ARB, even at low doses, though its protective effect on urinary protein is not as good as that of ACEI/ARB.

Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Biphenyl Compounds; Creatinine; Drug Combinations; Heart Failure; Humans; Kidney; Renal Insufficiency, Chronic; Stroke Volume; Tetrazoles; Valsartan; Ventricular Function, Left

The association between cardiac complications, such as heart failure (HF), and chronic kidney disease (CKD) is well known. In this study, we examined the effectiveness and safety of treatment with neprilysin inhibition in patients with advanced chronic kidney disease (stage 3b-4).. This single-centre, longitudinal, retrospective study of 31 months duration involved consecutive patients with CKD and HF with a reduced ejection fraction (HFrEF) who started treatment with sacubitril/valsartan. Glomerular filtration rate (GFR), cardiovascular risk factors, proteinuria, potassium, echocardiographic parameters and admissions for heart failure were analysed.. The study comprised 25 patients with a median age of 73.2 ± 5.9 years. The most frequent aetiology of heart failure was ischemic heart disease. The median GFR was 29.4 ± 8.3 ml/min/1.73 m. This study shows that sacubitril/valsartan may play a beneficial role in patients who have advanced CKD and HFrEF, with a satisfactory safety profile.

Topics: Aged; Aminobutyrates; Biphenyl Compounds; Drug Combinations; Heart Failure; Humans; Renal Insufficiency, Chronic; Retrospective Studies; Stroke Volume; Valsartan; Ventricular Function, Left