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Introduction: In this retrospective analysis, we evaluate the effectiveness of the potassium (K+) binder sodium zirconium cyclosilicate (SZC) in maintaining normokalemia and facilitating the initiation, optimization, and maintenance of renin–angiotensin–aldosterone system inhibitors (RAASi) in patients with heart failure (HF) with reduced ejection fraction (HFrEF). Methods: A total of 44 patients with HFrEF and a history of hyperkalemia who were receiving SZC to enable the prescription of RAASi were identified from two district general hospital sites. Retrospective analysis was performed to determine biochemical response, alterations in pharmacotherapy, and subsequent HF outcomes following initiation of SZC. Results: Mean K+ was reduced by 0.9 mmol/L within 1 month of initiation of SZC; mean K+ after 12 months of treatment was 4.8 mmol/L with a median (interquartile range) duration of treatment of 13 (8.4–15.1) months. Following SZC treatment, 100% of patients received an angiotensin receptor–neprilysin inhibitor (18% increase) and 93% received a mineralocorticoid receptor antagonist (41% increase), with 59% and 37% achieving guideline-recommended dosing, respectively. Ninety-one percent of patients were able to receive triple or quadruple therapy with the addition of a beta-blocker and a sodium glucose co-transporter 2 inhibitor. Reduced rates of hospitalization for HF (HHF) were observed with 12 episodes per 100 patient-years recorded (reduced from 21) in addition to improvements in mean left ventricular ejection fraction (29–36%) and median N-terminal pro-B-type natriuretic peptide (3458–2055 ng/L, 45% median reduction). Renal function (creatinine clearance increased from 48.4 to 49.3 ml/min) and systolic blood pressure (decreased from 124 to 122 mmHg) were similar following optimization, and no tolerability issues were identified. Conclusions: Extended real-world treatment with the K+ binder SZC was effective at maintaining normokalemia, and was associated with a greater uptake of RAASi, a reduced rate of HHF, and improvements in cardiac biomarkers in patients with HFrEF. [ABSTRACT FROM AUTHOR]

Resumen: Antecedentes y objetivo: La hiperpotasemia (HK) es una alteración electrolítica en la concentración de iones potasio (K+), cuyo riesgo aumenta en pacientes con enfermedad renal crónica (ERC) o insuficiencia cardiaca (IC) y/o en pacientes en tratamiento con inhibidores del sistema renina-angiotensina-aldosterona (iSRAA). Los nuevos quelantes orales de K+ ofrecen un tratamiento seguro y eficaz para mantener la normopotasemia en estos pacientes. El objetivo del análisis es estimar el coste-efectividad del ciclosilicato de sodio y zirconio (CSZ) para el tratamiento de la HK crónica en pacientes con ERC o IC vs. tratamiento estándar (poliestireno sulfonato cálcico y modificaciones del estilo de vida) desde la perspectiva del Sistema Nacional de Salud (SNS) español. Materiales y métodos: Se utilizaron dos modelos de microsimulación que reflejan la historia natural de la ERC y de la IC. En ambos modelos se realizó una simulación de forma individual de los niveles de K+. Con base en la eficacia (reducción de los niveles de K+), la calidad de vida de los pacientes (utilidades según estado de salud, y disutilidades de los eventos derivados de cada patología y los eventos adversos [EA] del tratamiento) y a los costes contemplados (coste del tratamiento para la HK, del tratamiento con iSRAA y su modificación, de los estados de salud, del manejo de los eventos derivados de cada patología, de los episodios de HK, y de los EA del tratamiento) (€, 2022), se obtuvieron resultados de beneficio clínico (años de vida ajustados por calidad [AVAC]) y costes. Se empleó un horizonte temporal de toda la vida del paciente y se aplicó una tasa de descuento del 3% para costes y resultados. Resultados: El CSZ resulta una opción más efectiva en ambas patologías, con una diferencia de AVAC de 0,476 en ERC, y de 0,978 en IC vs. tratamiento estándar, y supone un coste incremental de 3.616 € y 14.749 €, respectivamente, obteniéndose un ratio coste-utilidad incremental (RCUI) de 7.605 €/AVAC en ERC y 15.078 €/AVAC en IC. Conclusiones: El CSZ es una alternativa con una buena relación coste-efectividad para el tratamiento de la HK en pacientes con ERC o IC, teniendo en cuenta los valores de eficiencia de referencia empleados habitualmente en España. Abstract: Background and objective: Hyperkalemia (HK) is an electrolyte disturbance in the concentration of potassium ions (K+), whose risk increases in patients with chronic kidney disease (CKD) or heart failure (HF) and/or in patients being treated with renin-angiotensin-aldosterone system inhibitors (RAASi). The new oral K+ chelators offer a safe and effective treatment to maintain normokalemia in these patients. The objective of the analysis is to estimate the cost-effectiveness of sodium zirconium cyclosilicate (SZC) for the treatment of chronic HK in patients with CKD or HF versus standard treatment (calcium polystyrene sulfonate and lifestyle modifications) from the perspective of the Spanish National Health System. Materials and methods: Two microsimulation models reflecting the natural history of CKD and HF were used. In both models, K+ levels were simulated individually. Based on efficacy (reduction of K+ levels), quality of life of patients (utilities according to health states, and disutilities of events derived from each pathology and adverse events [AEs] of treatment) and costs considered (cost of treatment for HK, of RAASi treatment and its modification, health states, management of events derived from each pathology, HK episodes, and AEs treatment) (€, 2022), clinical benefit (quality-adjusted life years [QALYs]) and cost results were obtained. A time horizon of the patient's lifetime was used and a discount rate of 3% was applied for costs and outcomes. Results: SZC is a more effective option in both pathologies, with a difference in QALYs of 0.476 in CKD and 0.978 in HF compared to standard treatment, and it represents an incremental cost of € 3,616 and € 14,749, respectively, obtaining an incremental cost-utility ratio of € 7,605 /QALY in CKD and € 15,078 /QALY in HF. Conclusions: SZC is a cost-effective alternative for the treatment of HK in patients with CKD or HF, taking into account the reference efficiency values commonly used in Spain.

Introduction: Sodium zirconium cyclosilicate (SZC) is a nonabsorbed cationexchanger approved in China for the treatment of hyperkalemia [HK; serum potassium (sK+) levels >5.0 mmol/L]. This is the first real-world study aimed to assess the effectiveness, safety, and treatment patterns of SZC in Chinese patients with HK. Here we present the results of the first interim analysis. Methods: This multicenter, prospective, cohort study included patients aged =18 years with documented HK within 1-year before study enrollment day. These patients were followed up for 6 months from the enrollment day after initiating SZC treatment. The treatment was categorized into correction phase (FAS-P1) and maintenance phase (FAS-P2 new and ongoing users). Subgroup analysis was performed in patients on hemodialysis (FAS-H). The primary objective was evaluation of safety profile of SZC; secondary objectives included assessment of treatment patterns of SZC and its effectiveness. Results: Of 421 screened patients, 193, 354, and 162 patients were enrolled in the FAS-P1, FAS-P2, and FAS-H groups, respectively. sK+ levels were reduced significantly from 5.9 mmol/L to 5.0 mmol/L after the correction phase. For the maintenance phase, the mean sK+ levels were maintained at 5.2 mmol/L and 5.0 mmol/L in the FAS-P2 new and ongoing user, respectively, and 5.3 mmol/L in the FAS-H subgroup. A considerable proportion of patients showed normokalemia after 48 h of SZC treatment (FAS-P1:51.3%) which was maintained up to 6 months in the maintenance phase (FAS-P2:44%). SZC was well-tolerated. Conclusion: SZC was effective and safe for the treatment of HK in real-world clinical practice in China. [ABSTRACT FROM AUTHOR]

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INTRODUCTION: Hyperkalemia (HK) may result in disruptions of guidelines-concordant renin-angiotensin-aldosterone system inhibitors (RAASi), a standard of care in persons with chronic kidney disease (CKD). Such disruptions-dose reduction or discontinuation-diminish the benefits of RAASi, placing patients at risk of serious events and renal dysfunction. This real-world study evaluated RAASi modifications among patients who initiated sodium zirconium cyclosilicate (SZC) for HK. METHODS: Adults (≥ 18 years) initiating outpatient SZC (index date) while on RAASi were identified from a large US claims database (January 2018-June 2020). RAASi optimization (maintain same or up-titration of RAASi dosage), non-optimization (down-titration of RAASi dosage or discontinuation), and persistence were descriptively summarized following index. Predictors of RAASi optimization were assessed using multivariable logistic regression models. Analyses were conducted by subgroups, including patients without end-stage kidney disease (ESKD), with CKD, and with CKD + diabetes. RESULTS: A total of 589 patients initiated SZC during RAASi therapy (mean age 61.0 years, 65.2% male), and 82.7% patients (n = 487) kept RAASi after index (mean follow-up  = 8.1 months). Most patients (77.4%) optimized RAASi therapy after initiating SZC; 69.6% maintained the same dosage while 7.8% had up-titrations. A similar rate of RAASi optimization was observed among subgroups without ESKD (78.4%), with CKD (78.9%), and with CKD + diabetes (78.1%). At 1-year post-index, 73.9% of all patients who optimized RAASi were still on therapy, while only 17.9% of patients who did not optimize therapy were still on a RAASi. Among all patients, predictors of RAASi optimization included fewer prior hospitalizations (odds ratio = 0.79, 95% CI [0.63-1.00]; p

BackgroundThe KBindER (K+ Binders in Emergency Room and hospitalized patients) clinical trial is the first head-to-head evaluation of oral potassium binders (cation-exchange resins) for acute hyperkalemia therapy.MethodsEmergency room and hospitalized patients with a blood potassium level ≥ 5.5 mEq/L are randomized to one of four study groups: potassium binder drug (sodium polystyrene sulfonate, patiromer, or sodium zirconium cyclosilicate) or nonspecific laxative (polyethylene glycol). Exclusion criteria include recent bowel surgery, ileus, diabetic ketoacidosis, or anticipated dialysis treatment within 4 h of treatment drug. Primary endpoints include change in potassium level at 2 and 4 h after treatment drug. Length of hospital stay, next-morning potassium level, gastrointestinal side effects and palatability will also be analyzed. We are aiming for a final cohort of 80 patients with complete data endpoints (20 per group) for comparative statistics including multivariate adjustment for kidney function, diabetes mellitus, congestive heart failure, metabolic acidosis, renin-angiotensin-aldosterone system inhibitor prescription, and treatment with other agents to lower potassium (insulin, albuterol, loop diuretics).DiscussionThe findings from our study will inform decision-making guidelines on the role of oral potassium binders in the treatment of acute hyperkalemia.Trial registrationClinicalTrials.gov Identifier: NCT04585542 . Registered 14 October 2020.

Background: Patiromer and sodium zirconium cyclosilicate (SZC) are 2 oral potassium binders approved for chronic hyperkalemia. It is unknown if one is more effective at reducing serum potassium than the other in acute hyperkalemia. Objective: The objective of this study was to determine if there was a difference between patiromer and SZC in the reduction of serum potassium in patients with acute hyperkalemia. Methods: This was a single-center, retrospective, observational study. Patients with a nonhemolyzed serum potassium level of 5.5 mEq/L or greater and received at least one dose of patiromer or SZC were included. The primary outcome was to determine the difference in effectiveness between patiromer and SZC in lowering of serum potassium 6 to 24 hours after administration. Secondary outcomes included description of total dosage received in 24 hours and incidence of electrolyte changes. Results: A total of 200 patients were included in this study, with 100 patients in each group. Serum potassium was significantly reduced by both patiromer (−1.2 mEq/L, 95% confidence interval [CI]: −2.3 to −0.2) and SZC (−0.8 mEq/L, 95% CI: −1.0 to −0.7), but there was no difference between the 2 medications in the amount of potassium reduction (P = 0.464). No clinically significant differences in electrolyte changes were seen. Conclusions and Relevance: This study represents the first head-to-head comparison of patiromer and SZC in the setting of acute hyperkalemia. No difference in effectiveness between patiromer and SZC in reducing serum potassium was seen. Both agents can be considered in acute hyperkalemia management. [ABSTRACT FROM AUTHOR]

Inpatient treatment of hyperkalaemia with insulin and dextrose can be complicated by iatrogenic hypoglycaemia. We sought to assess the incidence of hypoglycaemia in hospitalised patients with renal disease and assess the impact of the introduction of a local guideline incorporating the use of sodium zirconium cyclosilicate (SZC) for patients with moderate hyperkalaemia. After establishing a significant burden of hypoglycaemia in the initial observation period, a requirement for hourly capillary blood glucose monitoring (for up to 6 h) following the administration of insulin for hyperkalaemia was incorporated into the guidelines. The two-fold introduction of SZC alongside changes in patient care after the administration of insulin/dextrose resulted in more appropriate use of insulin/dextrose, as well as a significant (73%) reduction in the iatrogenic burden of hypoglycaemia (P = 0.04). [ABSTRACT FROM AUTHOR]

L'hyperkaliémie, fréquente en pratique clinique courante, est un facteur de risque majeur de mortalité. Elle affecte principalement les patients présentant une insuffisance rénale chronique (IRC), un diabète ou recevant un traitement par inhibiteurs du système rénine-angiotensine-aldostérone (iSRAA). La prise en charge thérapeutique a pour objectif non seulement d'éviter les complications de l'hyperkaliémie, mais aussi d'éviter l'arrêt des traitements cardio- et néphroprotecteurs comme les iSRAA. L'emploi du polystyrène sulfonate, largement prescrit, est souvent limité par l'acceptabilité des patients. Des données récentes sont venues mettre en doute son innocuité, notamment sa tolérance digestive. Deux nouvelles molécules échangeuses de potassium ont fait leur apparition, le patiromer et le sulfonate de zirconium. Leur intérêt en pratique clinique ainsi que leur acceptabilité en cas de prescription prolongée, restent à démontrer. L'association d'un diurétique thiazidique ou d'un inhibiteur du cotransporteur sodium-glucose de type 2 (iSGLT2) au traitement par iSRAA dans l'IRC, peut également permettre de mieux contrôler la kaliémie. Il n'existe pas à l'heure actuelle de recommandations pour positionner les différents traitements hypokaliémiants. Le choix de ces traitements doit s'adapter aux pathologies du patient et tenir compte des autres effets attendus de ces molécules. Hyperkalemia is common in everyday clinical practice, and is a major risk factor for mortality. It mainly affects patients with chronic renal failure (CKD), diabetes or receiving treatment with inhibitors of the renin-angiotensin-aldosterone system (iRAAS). Therapeutic management aims not only to avoid the complications of hyperkalemia, but also to avoid discontinuation of cardio- and nephroprotective treatments such as iRAAS. The use of polystyrene sulfonate, widely prescribed, is often limited by patient acceptability. Recent data have cast doubt on its safety, particularly in terms of digestive tolerance. Two new potassium exchange molecules have appeared on the market: patiromer and zirconium sulfonate. Their value in clinical practice, and their acceptability in the event of prolonged prescription, remain to be demonstrated. The combination of a thiazide diuretic or an inhibitor of the sodium-glucose cotransporter type 2 (iSGLT2) with iRAAS therapy in CKD, may also improve control of kalemia. At present, there are no recommendations for the positioning of the various hypokalemic treatments. The choice of these treatments must be adapted to the patient's pathologies and consider the other expected effects of these molecules. [ABSTRACT FROM AUTHOR]

Background: Oral potassium binders have a role in the management of acute hyperkalemia among hospitalized patients. However, with therapeutic additions to this class, there is insufficient evidence between potassium binders to support a standard of care recommendation for use in this acute setting. Objective: The purpose of this study was to compare the acute potassium lowering effects of sodium zirconium cyclosilicate (SZC) and sodium polystyrene sulfonate (SPS). Methods: A retrospective review of admitted patients who received SZC or SPS was conducted after exemption from the Institutional Review Board. Patients with baseline potassium values less than 5.1 mmol/L or factors contributing to potentially false report of serum potassium were excluded. The primary outcome was the average change in potassium from baseline to 24 hours following potassium binder administration. Secondary outcomes compared changes to potassium from baseline to various time periods after administration, presence of electrolyte changes, and documentation of serious adverse events. Results: A total of 246 patients were included, with 128 receiving SZC and 118 receiving SPS. Mean change in serum potassium (mmol/L) at 24 hours was not significant between binders (−.78 vs −.91; P =.22). Secondary efficacy and safety outcomes were also similar between groups. A total of 5 serious adverse events were reported, occurring only in the SPS group. Conclusion: SZC and SPS have comparable effects in acute potassium reduction, with serious gastrointestinal adverse events documented only in SPS patients. Health systems may consider this data in determining medication formularies or during order set development. [ABSTRACT FROM AUTHOR]

Background: Crush Syndrome (CS), a severe trauma resulting from prolonged muscle compression, is commonly seen in large-scale disasters such as earthquakes. It not only causes localized tissue damage but also triggers electrolyte imbalances, particularly hyperkalemia, increasing the risk of early mortality. This study aims to assess the early intervention effects of Sodium Zirconium Cyclosilicate (SZC) on hyperkalemia in rat CS model. Methods: A rat CS model was established using a self-developed multi-channel intelligent small-animal crush injury platform. Rats in the experimental groups were treated with varying doses of SZC before compression and immediately post-decompression. The efficacy of SZC was evaluated by continuous monitoring of blood potassium levels and survival rates. Serum creatinine (Cre) and blood urea nitrogen (BUN) levels were analyzed, and renal damage was assessed through histopathological examination. Results: SZC treatment significantly reduced blood potassium levels and improved survival rates in rats. Compared to the placebo group, the SZCtreated rats showed a significant decrease in blood potassium levels at 6 and 12 h post-decompression, maintaining lower levels at 24 h. Biochemical analysis indicated no significant impact of SZC on renal function, with no notable differences in Cre and BUN levels between groups. Histopathological findings revealed similar levels of renal damage in both groups. Conclusion: SZC demonstrates significant early intervention effects on hyperkalemia in a rat model of crush injury, effectively improving survival rates without adverse effects on renal function. These results provide a new strategic direction for the clinical treatment of Crush Syndrome and lay the foundation for future clinical applications. [ABSTRACT FROM AUTHOR]

Background This observational cohort study compared the likelihood of maintained (stabilized/up-titrated) renin–angiotensin–aldosterone system inhibitor (RAASi) therapy at 6 months following hyperkalaemia in patients with chronic kidney disease (CKD) and/or heart failure (HF) from the USA, Japan and Spain who received sodium zirconium cyclosilicate (SZC) for at least 120 days, relative to those with no prescription for a potassium (K+) binder. Methods Using health registers and hospital medical records, patients with CKD and/or HF receiving RAASi therapy who experienced a hyperkalaemia episode were identified. Propensity score (PS) matching (1:4) was applied to balance the SZC cohort to the no K+ binder cohort on baseline characteristics. Logistic regression analysis was performed to compare the odds of maintained RAASi therapy at 6 months in the SZC versus no K+ binder cohorts. Results The PS-matched SZC cohort included 565 (USA), 776 (Japan) and 56 (Spain) patients; the no K+ binder cohort included 2068, 2629 and 203 patients, respectively. At 6 months, 68.9% (USA), 79.9% (Japan) and 69.6% (Spain) in the SZC cohorts versus 53.1% (USA), 56.0% (Japan) and 48.3% (Spain) in the no K+ binder cohorts had maintained RAASi therapy. Meta-analysed across countries, the odds ratio of maintained RAASi therapy in the SZC cohort versus no K+ binder cohort was 2.56 (95% confidence interval 1.92–3.41; P  < .0001). Conclusions In routine clinical practice across three countries, patients treated with SZC were substantially more likely to maintain guideline-concordant RAASi therapy at 6 months following hyperkalaemia relative to patients with no K+ binder treatment. [ABSTRACT FROM AUTHOR]

Introduction: Hyperkalaemia (HK) is prevalent among patients with chronic kidney disease (CKD) and chronic heart failure, especially if they are treated with renin‐angiotensin‐aldosterone system inhibitors (RAASi). This study evaluated the cost‐effectiveness of a newly developed anti‐HK therapy, sodium zirconium cyclosilicate (SZC), to the current standard of care for treating HK in advanced CKD patients from the Singapore health system perspective. Methods: We adapted a global microsimulation model to simulate individual patients' potassium level trajectories with baseline potassium ≥5.5 mmol/L, CKD progression, changes in treatment, and other fatal and non‐fatal events. Effectiveness data was derived from ZS‐004 and ZS‐005 trials. Model parameters were localised using CKD patients' administrative and medical records at the Singapore General Hospital Department of Renal Medicine. We estimated the lifetime cost and quality‐adjusted life years (QALYs) of each HK treatment, and the incremental cost‐effectiveness ratio of SZC. Results: SZC demonstrated cost‐effectiveness with an incremental cost‐effectiveness ratsio of SGD 45 068 per QALY over a lifetime horizon, below the willingness‐to‐pay threshold of SGD 90 000 per QALY. Notably, SZC proved most cost‐effective for patients with less severe CKD who were concurrently using RAASi. Sensitivity analyses confirmed the robustness of the findings, accounting for alternative parameter values and statistical uncertainty. Conclusion: This study establishes the cost‐effectiveness of SZC as a treatment for HK, highlighting its potential to mitigate the risk of hyperkalaemia and optimise RAASi therapy. These findings emphasise the value of integrating SZC into the Singapore health system for improved patient outcomes and resource allocation. Summary at a glance: The use of sodium zirconium cyclosilicate (SZC) can potentially lower the risk of hyperkalaemia among patients with chronic kidney disease and facilitate the optimization of RAASi therapy. This study demonstrated the incremental cost‐effectiveness of SZC relative to usual care (sodium polystyrene sulfonate) from the Singapore healthcare system perspective. [ABSTRACT FROM AUTHOR]

Background: Sodium zirconium cyclosilicate (SZC), an ion-exchange resin, is effective in the control of hyperkalemia in adults with chronic kidney disease (CKD); reports of use in children are limited. Prolonged therapy with SZC to relax dietary potassium restriction in CKD has not been examined. Methods: We conducted a retrospective chart review of patients 6 months to 18 years of age with CKD stage 4–5 or on dialysis (5D) administered SZC for sustained hyperkalemia (potassium ≥ 5.5 mEq/L, three consecutive values). Patients received SZC (0.5–10 g per dose; age-based) either short-term (< 30 days) or long-term (> 30 days). Results: Twenty patients with median age 10.8 (inter-quartile range 3.9, 13.4) years were treated with SZC. Short-term SZC, for 5 (3, 19) days, was associated with safe management of dialysis catheter insertions (n = 5) and access dysfunction (n = 4), and was useful during palliative care (n = 1). Serum potassium levels decreased from 6.7 (6.1, 6.9) to 4.4 (3.7, 5.2) mEq/L (P < 0.001). Long-term SZC for 5.3 (4.2, 10.1) months achieved decline in serum potassium from 6.1 (5.8, 6.4) to 4.8 (4.2, 5.4) mEq/L (P < 0.001). SZC use was associated with liberalization of diet (n = 6) and was useful in patients with poor adherence to dietary restriction (n = 3). Adverse events or edema were not observed; serum sodium and blood pressure remained stable. Conclusions: SZC was safe and effective for the management of acute and chronic hyperkalemia in children with CKD4-5/5D. Its use was associated with relaxation of dietary potassium restriction. Studies to examine its routine use to improve diet and nutritional status in children with CKD are required. [ABSTRACT FROM AUTHOR]

Background: We shall assess the efficacy and safety of patiromer in subjects with heart failure (HF) in randomized controlled trials (RCTs). Methods: The protocol has been developed supported the PRISMA-P checklist by using (PICO [population, intervention, comparators, and outcome]) items, for adult subjects with HF who have received patiromer in RCTs versus SZC or placebo to attain specific endpoint of control of hyperkalemia. The subjects with HF (population) receiving patiromer (intervention) are compared to placebo or other potassium binders (comparators), like sodium zirconium cyclosilicate (ZS-9, SZC, Lokelma®) for the non-inferiority or superiority in terms of effects on hyperkalemia (outcome) and alter in potassium serum levels. Results: Patiromer may provide an efficient treatment for hyperkalemia in subjects with HF receiving angiotensin-converting enzyme inhibitor (ACEi), angiotensin receptor blocker (ARB) and/or mineralocorticoids/aldosterone antagonists (MRA/AA). Patiromer may facilitate the clinical utility of RAAS inhibitors without discontinuation or interruption of therapy in subjects with HF. Patiromer may enable dose titration of AA without the danger of hyperkalemia. Patiromer is anticipated to halt recurrence of hyperkalemia in subjects with HF. Conclusion: Patiromer may provide safe and effective therapy for prevention, maintenance, management, and prevent recurrence of hyperkalemia in subjects with HF as compared to the other comparators. [ABSTRACT FROM AUTHOR]

Heart failure is a chronic and invalidating syndrome that affects tens of millions of people worldwide with significant socio-economic ramifications for the health care systems. Significant progress in the understanding of the pathophysiology of heart failure has allowed the gradual introduction of several drug classes for the management of such patients. Beta-blockers, mineralocorticoid receptor antagonists, angiotensin receptor neprilysin inhibitors, and sodium–glucose-cotransporter 2 inhibitors are all considered pillars of the guideline-directed medical therapy for heart failure. Despite remarkable improvements in the morbidity and mortality of heart failure, however, many patients still develop clinically significant hyperkalemia during combined treatment with those four pharmacological pillars. The consequence is often a down-titration or discontinuation of one or more crucial drugs, which in turns leads to a considerable increase in the risk of cardiovascular events, dialysis, and all-cause mortality. This paper will explore novel approaches for the management of hyperkalemia in heart failure, including closer monitoring of potassium levels, early review of drugs that might increase the risk of hyperkalemia, and pharmacological treatment of hyperkalemia, with a special emphasis on sodium–glucose-cotransporter 2 inhibitors and potassium-binding agents, including patiromer and sodium zirconium cyclosilicate. [ABSTRACT FROM AUTHOR]

Resumen: La hiperpotasemia es una alteración electrolítica frecuente con consecuencias potencialmente graves a corto, medio y largo plazo, tanto en términos de morbilidad y mortalidad como de consumo de recursos del Sistema Nacional de Salud. El abordaje de la hiperpotasemia por diversas especialidades médicas y la reciente disponibilidad de nuevos tratamientos farmacológicos específicos hace necesaria una acción unificada y actualizada. El presente documento de consenso entre las sociedades científicas más directamente implicadas en el abordaje de la hiperpotasemia (Sociedad Española de Cardiología, Sociedad Española de Endocrinología y Nutrición, Sociedad Española de Medicina Interna, Sociedad Española de Medicina de Urgencias y Emergencias y Sociedad Española de Nefrología) repasa, en primer lugar, aspectos básicos del balance de potasio y de la potasemia, centrándose posteriormente en el concepto, epidemiología, fisiopatología, y abordaje diagnóstico y terapéutico de la hiperpotasemia. Se han revisado las evidencias y los principales estudios publicados con el objetivo de que sea una herramienta útil en el abordaje multidisciplinar del paciente con hiperpotasemia. Abstract: Hyperkalaemia is a common electrolyte imbalance with potentially serious short-, medium- and long-term consequences on morbidity and mortality rates and the use of national health service resources. The fact that different medical specialities can manage hyperkalaemia makes it important to have a unified approach, and the recent availability of new specific drug treatments means that the approach needs to be updated. This consensus document from the scientific societies most directly involved in the management of hyperkalaemia (Sociedad Española de Cardiología [Spanish Society of Cardiology], Sociedad Española de Endocrinología y Nutrición [Spanish Society of Endocrinology and Nutrition], Sociedad Española de Medicina Interna [Spanish Society of Internal Medicine], Sociedad Española de Medicina de Urgencias y Emergencias [Spanish Society of Emergency Medicine and Emergencies] and Sociedad Española de Nefrología [Spanish Society of Nephrology]) first of all reviews basic aspects of potassium balance and blood potassium. Then it goes on to focus on the concept, epidemiology, pathophysiology and diagnostic and therapeutic approaches to hyperkalaemia. The available evidence and the main published studies have been reviewed with the aim of providing a useful tool in the multidisciplinary approach to patients with hyperkalaemia.

Problem: Hyperkalemia is a serious condition among intra‐abdominal transplant recipients, and the safety and efficacy of sodium zirconium cyclosilicate (SZC) for its management during the early post‐transplant period are not well‐established. Methods: Adults who received at least one 10‐g dose of SZC within 14 days after an intra‐abdominal transplant between January 2020 and July 2022 were included in our study. The primary outcome was the change in potassium (K+) levels following the first SZC dose. Other analyses explored adjunctive potassium‐lowering therapies, potential gastrointestinal complications, and patient subgroups based on therapy and transplant type. Results: Among the recipients (n = 46), 11 were kidney recipients, 26 were liver recipients, seven were simultaneous liver/kidney recipients, and two were simultaneous pancreas/kidney recipients. The mean time to first dose post‐transplant was 7.6 (±4) days, and the mean change in serum K+ after the initial SZC dose was −.27 mEq (p =.001). No gastrointestinal complications were observed following the SZC dose. The mean increase in serum bicarbonate was.58 mEq (p =.41) following the first dose of SZC. Four kidney recipients required dialysis following the SZC dose. Conclusion: This study represents the largest investigation on the use of SZC in transplant recipients. A single 10‐g dose of SZC reduced serum K+ levels in all subgroups, while the use of adjunctive K+‐lowering therapies did not provide additional reduction beyond the effects of SZC. Importantly, no gastrointestinal complications were observed. These findings suggest that SZC may be a safe and promising therapeutic option for hyperkalemia management following solid organ transplantation. [ABSTRACT FROM AUTHOR]

Study Objective: To assess the efficacy of single‐dose sodium zirconium cyclosilicate (SZC) compared to the FDA approved three times daily (TID) dosing and to single‐dose sodium polystyrene sulfonate (SPS) for the management of asymptomatic hyperkalemia in hospitalized patients. Design: Single‐center retrospective chart review. Setting: University of Florida Health Jacksonville, a 695‐bed academic medical center in Jacksonville, FL, between June 15, 2018 and August 15, 2021. Patients: Three hundred fifty‐one adult patients who were admitted to any hospital unit in the specified timeframe and received one of three interventions for asymptomatic hyperkalemia (serum potassium ≥4.7 mmol/L) were included in this study. Intervention: The interventions compared were single‐dose SZC 10 g, SZC 10 g × 3 doses (30 g total) within 24 h, or SPS 15–30 g once. Measurements and Main Results: The primary outcome was the proportion of patients achieving normokalemia (K+ 3.3–4.6 mmol/L) within 12–30 h of the first study dose. Secondary outcomes included average change in potassium within 12–30 h and 3–54 h from the first dose. The primary outcome was met in 68 patients (58.1%) in the SZC 10 g group, 51 (43.6%) in the SZC 10 g × 3 doses group, and 81 (69.2%) in the SPS 15–30 g group (p < 0.01). The average reduction in potassium in 12–30 h was 0.70 mmol/L, 0.78 mmol/L, and 0.99 mmol/L in the SZC 10 g, SZC 10 g × 3 doses, and SPS 15–30 g groups, respectively (p < 0.01). Conclusions: SZC 10 g once resulted in more patients achieving normokalemia compared to SZC 10 g × 3 doses but less than SPS (p < 0.01). Single‐dose SZC may be a reasonable option to manage asymptomatic hyperkalemia in the hospital setting, but achieving normokalemia with one dose may be less likely in patients with higher baseline potassium concentrations and impaired renal function. [ABSTRACT FROM AUTHOR]

• The impact of hyperkalemia in the down-titration or reduction of HF therapy is well known. • Patiromer and sodium zirconium cyclosilicate are new treatment available for hyperkalemia. • Patiromer and sodium zirconium cyclosilicate were significantly associated with heart failure therapy optimization, reduction of hyperkalemia events and reduction of mean potassium levels, albeit with a higher rate of hypokalemia events. • Trials evaluating whether this heart failure therapy optimization results in a lower incidence of major adverse cardiovascular events are now needed. Hyperkalemia often occurs among heart failure (HF) patients, particularly when treated with renin-angiotensin-aldosterone system inhibitors (RAASi). Even modest potassium levels variations raise the risk of mortality and prompt patients to discontinue disease-modifying treatment, as RAASi. Novel potassium binders (NPB), patiromer and sodium zirconium cyclosilicate, are effective in reducing potassium levels and are approved for the treatment of hyperkalemia in HF, but whether their use results in a real optimization of HF treatment remains to be seen. The aim of the present meta-analysis was to assess the efficacy of NPB on the optimization of RAASi therapy in HF patients. PubMed, Web of Science and Clinicaltrial.gov were searched without restrictions from inception to 06 August 2022 to identify valuable articles. The studies that met the inclusion criteria were analyzed. The prespecified primary outcome was the optimization of RAASi therapy in HF patients, defined as the proportion of patients on RAASi at the end of follow-up. Secondary outcomes were hyperkalemia events, reduction in potassium levels, and adverse drugs reactions. Six studies with a total of 1390 patients were included. NPB improved RAASi therapy optimization in HF by 14% (95% CI: 4–26%), decreased hyperkalemia events by 29% (95% CI: 55–92%), and reduced potassium levels by 0.31 mEq/L (95% CI: 0.18–0.44) compared to placebo, maintaining a good safety profile. NPB are effective in allowing RAASi therapy optimization in patients affected by HF, in reducing hyperkalemia events and potassium levels. CRD42022351811 URL: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=351811 NPB in HF: A new therapeutic approach for an old problem Caption: CI, confidence interval; GI, gastrointestinal; HF, heart failure; NPB, novel potassium binders; RAASi, RAAS inhibitors; RCT, randomized controlled trial; RR, relative risk; SZC, sodium zirconium cyclosilicate. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Potassium-binders patiromer and sodium zirconium cyclosilicate (SZC) are approved to treat hyperkalaemia, which is frequently observed in chronic kidney disease (CKD). Elevated blood pressure (BP) is common in CKD, due in part to impaired sodium excretion. The effect of patiromer, which exchanges calcium for potassium and SZC, which exchanges sodium or hydrogen for potassium, on BP was assessed in a CKD rat model. Methods: Thirty-six Sprague Dawley rats with 5/6 nephrectomy were randomised to three groups (n = 12/group) to receive 4 g/kg/day patiromer or SZC, or vehicle treatment, for 8 weeks. BP was determined by radiotelemetry and urinary protein and electrolytes were measured. Results: At Week 8, systolic BP (sBP) increased in all groups; however, patiromer led to a lower mean (standard deviation) sBP than vehicle or SZC (141 [2.9] vs 158 [5.2] or 162 [6.1] mm Hg, respectively, both p < 0.001), with no difference in sBP between vehicle and SZC (p = 0.08). Similar results were observed for diastolic BP. Serum potassium levels fell with SZC (p < 0.02), but not vehicle or patiromer. Urine potassium decreased with both patiromer and SZC versus vehicle (p < 0.01); urine sodium increased with SZC (p < 0.01); and urine calcium increased with patiromer (p < 0.01). Urine phosphorus decreased with patiromer (p < 0.01) but increased with SZC (p < 0.01). Patiromer resulted in less proteinuria than vehicle or SZC (both p < 0.017). Conclusions: After 8 weeks, treatment with patiromer resulted in lower BP in rats than vehicle or SZC. Further studies are needed to determine the mechanism of the differential effect of potassium binders on rat BP. [ABSTRACT FROM AUTHOR]

Background: Hyperkalemia is an electrolyte abnormality with potentially life-threatening consequences. Published data have shown that potassium-binding polymer patiromer (Veltassa) is associated with reduced rates of severe edema and hospitalization for heart failure compared with sodium zirconium cyclosilicate (SZC, Lokelma) when treating hyperkalemia. The aim of this study was to evaluate the possible costs associated with these interventions in the Spanish and UK settings. Methods: A cost-analysis model was developed in Microsoft Excel to compare the costs associated with patiromer and SZC for the management of hyperkalemia. Clinical event rates were taken from a published real-world comparative study, with the base case capturing the statistically significant reduction in severe edema with patiromer vs SZC and a sensitivity analysis also including the non-statistically significant reduction in hospitalization for heart failure. Country-specific costs, expressed in 2022 Euros (EUR) and British pounds sterling (GBP), were evaluated from a healthcare payer perspective and included pharmacy costs and costs of clinical events. Results: Patiromer may be associated with cost savings of EUR 107 and GBP 630 per patient-year of treatment vs SZC in Spain and the UK, respectively. The majority of cost savings were due to the possible lower daily cost of patiromer compared with SZC. Including the difference in heart failure hospitalization rates in a sensitivity analysis led to greater cost savings with patiromer over SZC, increasing to EUR 460 and GBP 902 in Spain and the UK, respectively. Extrapolation of patient-level economic outcomes to a population level found that patiromer was associated with annual cost savings of EUR 30.6 million in Spain, and GBP 801.7 million in the UK vs SZC. Conclusions: Patiromer has the potential to be cost saving vs SZC for the treatment of hyperkalemia in Spain and the UK based on the results of a real-world evidence analysis. [ABSTRACT FROM AUTHOR]

Introduction: Our model was conducted from Kuwaiti payer's perspective to provide evidence on the cost-effectiveness of Sodium zirconium cyclosilicate (SZC) versus patiromer to correct and maintain serum potassium (K+) in combination with renin‐angiotensin‐aldosterone system inhibitors (RAASis) with different dose titration in patients with chronic kidney disease/heart failure (CKD/HF) with/without renal replacement therapy (RRT). Methodology: The model was developed as a patient-level, fixed-time increment stochastic simulation to simulate the complexity of disease, including multiple coexisting and competing conditional risks. This model was established to compare SZC versus patiromer as a treatment for hyperkalemia (HK) among adult populations with underlying conditions of advanced CKD stages 3a–5 or HF to correct and maintain serum K + over a lifetime horizon. The clinical outcomes of SZC and patiromer were demonstrated through arm-specific K + trajectories extracted from the HARMONIZE trial and OPAL-HK trial, respectively. The utility data was captured from different studies. Direct medical cost was captured from local data from Kuwaiti hospitals. Sensitivity analyses were conducted to assess the uncertainty in the model. Results: Within different scenarios of CKD/HF, SZC was a cost-saving option, with/without RRT, whether one-off administration or repeated administration, except for one-off treatment administration among the HF cohort, which generated an incremental cost effectiveness ratio of KWD 331/quality adjusted life year (QALY). The incremental QALY of SZC ranged from 0.007 to 0.202. In addition, the savings observed with SZC fall within a range of KWD −60 to KWD −1,235 at serum K+ ≥ 5.1 mmol/L. Conclusion: The evidence generated by our model recommends the inclusion of SZC as a treatment option to correct HK and maintain normal serum K + level for CKD/HF patients within the Kuwaiti healthcare system. The costs saved from reducing frequent HK episodes, RAASis discontinuation/down titration, major cardiovascular events, and hospitalization offset the drug acquisition cost of SZC. [ABSTRACT FROM AUTHOR]

ObjectivesHyperkalemia most commonly develops in chronic kidney disease (CKD) or heart failure (HF) patients. Sodium zirconium cyclosilicate (SZC) is a new selective potassium (K+) binder for treating hyperkalemia. The aim of this study was to evaluate the cost-effectiveness of SZC vs. usual care for the treatment of hyperkalemia among CKD patients or HF patients in China.MethodsIndividual patient microsimulation models were constructed to simulate a CKD cohort until the initiation of renal replacement therapy (RRT) and a HF cohort across the lifetime horizon. K+ levels were based on two phase 3 clinical trials. Health state utility and event incidence rates were retrieved from literature. Drug costs and healthcare utilization costs were obtained from negotiated price, literature, and expert interviews. Costs and quality-adjusted life-years (QALYs) were both discounted at 5%. The main outcomes were overall costs, QALYs, and incremental cost-effectiveness ratio (ICER). The willingness-to-pay (WTP) threshold in China is CNY 80,976-242,928/QALY, which is one to three times the gross domestic product per capita. Sensitivity analyses were performed to characterize the models’ uncertainty.ResultsIn the HF cohort, the base case results revealed that SZC was associated with 2.86 QALYs and the total cost was CNY 92671.58; usual care was associated with 1.81 QALYs and CNY 54101.26. In the CKD cohort, SZC was associated with 3.23 QALYs and CNY 121416.82 total cost; usual care was associated with 2.91 QALYs and CNY 111464.57. SZC resulted in an ICER of CNY 36735.87/QALY for the HF cohort and CNY 31181.55/QALY for the CKD cohort, respectively. The one-way and probability sensitivity analyses found that the results were robust.ConclusionSZC is a cost-effective treatment compared to usual care in HF and CKD patients. SZC is an important novel treatment option for managing patients with hyperkalemia in China.

Sodium Zirconium Cyclosilicate (SZC) is commonly used for treating hyperkalemia because it sequesters gastrointestinal potassium ions, thereby reducing serum potassium levels. However, a less-discussed aspect of SZC is its radiopacity on x-ray-based imaging techniques. The European Medicines Agency (EMA) has only vaguely addressed this issue. Radiopaque substances like SZC can interfere with diagnostic imaging, creating challenges for clinicians and radiologists. We present the case of a 34-year-old Italian male to illustrate these concerns.

Hyperkalemia is a common electrolyte disorder in patients with chronic kidney disease (CKD) that increases in prevalence with the decline of glomerular fltration rate (GFR). Another risk of hyperkalemia is the use of renin-angiotensin-aldosterone system inhibitors (RAASi) and/or mineralocorticoid receptor antagonists (MRAs) in managing CKD and proteinuria. The treatment of chronic hyperkalemia is challenging especially for outpatients. Treatment options for hyperkalemia include the potassium exchange resins of which two new potassium binders, Patiromer Sorbitex Calcium, and Sodium Zirconium Cyclosilicate (SZC) have demonstrated their clinical efficacy in reducing serum potassium with a positive safety profile. The old potassium exchange resin sodium polystyrene sulfonate (Kayexalate™) has some negative side effects including colonic necrosis, hypomagnesemia, and hypernatremia. In this review and literature search, we compare the available oral potassium exchange resins, highlight their advantages and disadvantages and comment on efficacy and safety parameters specifically in CKD patients.

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Hyperkalemia is one of the most common electrolyte disorders in chronic kidney disease (CKD) and is associated with serious adverse outcomes. Hyperkalemia risk is even greater when CKD patients also have additional predisposing conditions such as diabetes or heart failure. Renin-angiotensin-aldosterone-system blockers are first-line treatments for cardio- and nephroprotection, but their use is often limited due to K+ elevation, resulting in high rates of discontinuation. This article provides an overview of factors interfering with K+ homeostasis and discusses recent data on newer therapeutic agents used for the treatment of hyperkalemia. A detailed literature search was performed in two major databases (PubMed/MEDLINE and Scopus) up to April 2023. Major clinical trials have tested new and promising kidney protective therapies such as sodium/glucose-cotransporter-2 inhibitors and mineralocorticoid-receptor-antagonists, with promising results. Until recently, the only treatment option for hyperkalemia was the cation-exchanging resin sodium-polystyrene-sulfonate. However, despite its common use, the efficacy and safety data of this drug in the long-term management of hyperkalemia are scarce. During the last decade, two novel orally administered K+-exchanging compounds (patiromer and sodium-zirconium-cyclosilicate) have been approved for the treatment of adults with hyperkalemia, as they both effectively reduce elevated serum K+ and maintain chronically K+ balance within the normal range with an excellent tolerability and no serious adverse events. [ABSTRACT FROM AUTHOR]

Introduction: Patients receiving cardiorenal-protective renin–angiotensin–aldosterone system inhibitors (RAASis) are at increased risk of developing hyperkalemia, which is associated with increased medical costs. The aim of this study was to evaluate the impact of adding sodium zirconium cyclosilicate (SZC) therapy on 3-month medical costs in patients who experienced hyperkalemia while receiving RAASi therapy. Methods: The retrospective OPTIMIZE II study used medical and pharmacy claims data from IQVIA PharMetrics® Plus. Patients aged ≥ 18 years who received SZC (≥ 60 day supply over 3 months' follow-up) and continued RAASi between July 2019 and December 2021 (Continue RAASi + SZC cohort) were 1:1 exact and propensity score matched with patients who discontinued RAASi after hyperkalemia diagnosis and did not receive SZC (Discontinue RAASi + no SZC cohort). The primary outcome was hyperkalemia-related medical costs to payers over 3 months; all-cause medical and pharmacy costs were also analyzed. Results: In the Continue RAASi + SZC (n = 467) versus Discontinue RAASi + no SZC (n = 467) cohort, there were significant reductions in mean per-patient hyperkalemia-related medical costs (reduction of $2216.07; p = 0.01) and all-cause medical costs (reduction of $6102.43; p < 0.001); mean hyperkalemia-related inpatient medical costs and all-cause inpatient and emergency department medical costs were significantly reduced. The reduction in all-cause medical cost in the Continue RAASi + SZC cohort offset an increase in the mean per-patient all-cause pharmacy cost (increase of $3117.71; p < 0.001). Conclusion: RAASi therapy has well-established cardiorenal benefits. In OPTIMIZE II, management of RAASi-induced hyperkalemia with SZC was associated with lower hyperkalemia-related and all-cause medical costs than RAASi discontinuation without SZC, demonstrating medical cost savings with maintaining RAASi therapy with SZC. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy of sodium zirconium cyclosilicate (SZC) in combination with insulin and glucose infusion in managing hyperkalemia. Methods: A total of 126 patients, who were admitted with hyperkalemia (= 5 mmol/L) to the Yongchuan District Hospital of Traditional Chinese Medicine, Chongqing, China from January 2021 to December 2022, were retrospectively studied. Participants were divided into three groups based on different potassium-lowering regimens, viz, SZC group (40 patients), insulin with glucose (IG) group (38 patients) and SZC + IG group (48 patients). Changes in potassium levels, other serum electrolytes (magnesium, sodium, phosphate, calcium), alanine aminotransferase (ALT) and albumin before and after treatment were recorded. Adverse reactions during treatment were also recorded. Results: Post-treatment, the potassium levels in all three groups exhibited a significant reduction when compared to pre-treatment values (p < 0.05). The SZC + IG group showed the highest efficacy, with a significant reduction in blood potassium levels observed 4 h after administration, which was more pronounced compared to other groups. The SZC + IG group, maintained potassium ion concentration at a normal level for a longer duration and no serious adverse reactions were observed during treatment. Conclusion: Intervention with SZC + IG lowers blood potassium levels, maintains it within normal range, and is more effective than the individual use of SZC or IG. A combination of sodium zirconium cyclosilicate, insulin and glucose infusion for treating hyperkalemia will need to be investigated further in a large-scale multicenter study. [ABSTRACT FROM AUTHOR]

Purpose Potassium binders are frequently utilized for the treatment of hyperkalemia in hospitalized patients; however, there is limited data directly comparing individual agents. The purpose of this study was to compare the effectiveness and safety of sodium polystyrene sulfonate (SPS) and sodium zirconium cyclosilicate (SZC) for hyperkalemia treatment in hospitalized patients. Methods This retrospective cohort study evaluated adult patients who were admitted within a 7-hospital health system and received SPS or SZC for a serum potassium level greater than 5.0 mEq/L. Patients receiving dialysis prior to SPS/SZC administration, those receiving other potassium-lowering medications within 6 hours prior to blood sampling for a repeat potassium level, and those started on kidney replacement therapy prior to sampling for a repeat potassium level were excluded. Results Following evaluation of 3,903 patients, the mean reduction in serum potassium 4 to 24 hours after binder administration was 0.96 mEq/L with SPS and 0.78 mEq/L with SZC (P < 0.0001). The median dose of SPS was 30 g (interquartile range [IQR], 15-30 g) while the median (IQR) dose of SZC was 10 g (10-10 g). Resolution of hyperkalemia within 24 hours was achieved in a higher percentage of patients with use of SPS (74.9%) versus SZC (68.8%) (P < 0.001). Conclusion One of the largest comparisons of SPS and SZC conducted to date, this study demonstrated the effectiveness and safety of both agents. While a statistically greater reduction in serum potassium was observed with use of SPS, there was significant dosing variability among agents that limited the ability to directly compare specific doses. Further investigation is needed to determine the optimal dose of each agent for acute hyperkalemia management. This data will inform clinical decisions about the choice of potassium binder for acute hyperkalemia. [ABSTRACT FROM AUTHOR]

Background: Sodium zirconium cyclosilicate (SZC) is an inorganic zirconium silicate compound that selectively exchanges potassium for hydrogen and sodium. "Once" doses of SZC (with option to redose) in patients with hyperkalemia in hospitalized settings have not been evaluated. We hypothesized that a once dose of SZC would be non-inferior to sodium polystyrene sulfonate (SPS) in reducing serum potassium. Objective: The objective of our study is to evaluate the effect of a "once" dose of SZC when compared with SPS in reducing serum potassium levels. Methods: This was a retrospective analysis of patients who received either a "once" dose of SZC or single or repeated doses of SPS for hyperkalemia. The primary endpoint was mean absolute reduction in the first serum potassium value at least 4 hours after administration. The secondary efficacy endpoints were the rate of additional potassium-lowering therapies and the rate of normokalemia within 48 hours. Safety endpoints were the incidence of electrolyte abnormalities, hypoglycemia, hypertension, hypotension, and colonic necrosis. Results: A total of 260 patients were included in the analysis. The mean initial serum potassium was similar between groups (5.6 ± 0.4). The absolute serum potassium reduction was −0.88 ± 0.64 mEq/L and −0.75 ± 0.65 mEq/L with SZC and SPS, respectively. The "once" regimen of SZC demonstrated non-inferiority compared with SPS (P < 0.0001). The proportion of patients achieving normokalemia within 48 hours and the proportion of patients receiving additional potassium-lowering therapies did not differ between groups. Conclusion and Relevance: The "once" dose regimen (with redose option) of SZC was non-inferior to the "once" or repeated dosing regimen of SPS with regard to absolute potassium reduction. There were no significant differences in the rate of additional potassium-lowering therapies and the rate of normokalemia at 48 hours. The incidence of hypertension was less common among patients who received SZC. [ABSTRACT FROM AUTHOR]

Abstract Aims Several patients with heart failure and reduced ejection fraction (HFrEF) do not receive renin–angiotensin–aldosterone system (RAAS) inhibitors at the recommended dose or at all, frequently due to actual or feared hyperkalaemia. Sodium zirconium cyclosilicate (SZC) is an orally administered non‐absorbed intestinal potassium binder proven to lower serum potassium concentrations. Methods and results PRIORITIZE‐HF was an international, multicentre, parallel‐group, randomized, double‐blind, placebo‐controlled study to evaluate the benefits and risks of using SZC to intensify RAAS inhibitor therapy. Patients with symptomatic HFrEF were eligible and randomly assigned to receive SZC 5 g or placebo once daily for 12 weeks. Doses of study medication and RAAS inhibitors were titrated during the treatment period. The primary endpoint was the proportion of patients at 12 weeks in the following categories: (i) any RAAS inhibitor at less than target dose, and no MRA; (ii) any RAAS inhibitor at target dose and no MRA; (ii) MRA at less than target dose; and (iv) MRA at target dose. Due to challenges in participant management related to the COVID‐19 pandemic, the study was prematurely terminated with 182 randomized patients. There was no statistically significant difference in the distribution of patients by RAAS inhibitor treatment categories at 3 months (P = 0.43). The proportion of patients at target MRA dose was numerically higher in the SZC group (56.4%) compared with the placebo group (47.0%). Overall, SZC was well tolerated. Conclusions PRIORITIZE‐HF was terminated prematurely due to COVID‐19 and did not demonstrate a statistically significant increase in the intensity of RAAS inhibitor therapies with the potassium‐reducing agent SZC compared with placebo.

Abstract Background The KBindER (K+ Binders in Emergency Room and hospitalized patients) clinical trial is the first head-to-head evaluation of oral potassium binders (cation-exchange resins) for acute hyperkalemia therapy. Methods Emergency room and hospitalized patients with a blood potassium level ≥ 5.5 mEq/L are randomized to one of four study groups: potassium binder drug (sodium polystyrene sulfonate, patiromer, or sodium zirconium cyclosilicate) or nonspecific laxative (polyethylene glycol). Exclusion criteria include recent bowel surgery, ileus, diabetic ketoacidosis, or anticipated dialysis treatment within 4 h of treatment drug. Primary endpoints include change in potassium level at 2 and 4 h after treatment drug. Length of hospital stay, next-morning potassium level, gastrointestinal side effects and palatability will also be analyzed. We are aiming for a final cohort of 80 patients with complete data endpoints (20 per group) for comparative statistics including multivariate adjustment for kidney function, diabetes mellitus, congestive heart failure, metabolic acidosis, renin-angiotensin-aldosterone system inhibitor prescription, and treatment with other agents to lower potassium (insulin, albuterol, loop diuretics). Discussion The findings from our study will inform decision-making guidelines on the role of oral potassium binders in the treatment of acute hyperkalemia. Trial registration ClinicalTrials.gov Identifier: NCT04585542 . Registered 14 October 2020.

Abstract It is well established that an elevated potassium level (hyperkalemia) is associated with a risk of adverse events including morbidity, mortality and healthcare system cost. Hyperkalemia is commonly encountered in many chronic conditions including kidney disease, diabetes and heart failure. Furthermore, hyperkalemia may result from the use of renin-angiotensin-aldosterone system inhibitors (RAASi), which are disease-modifying treatments for these conditions. Therefore, balancing the benefits of optimizing treatment with RAASi while mitigating hyperkalemia is crucial to ensure patients are optimally treated. In this review, we will briefly discuss the definition, causes, epidemiology and consequences of hyperkalemia. The majority of the review will be focused on management of hyperkalemia in the acute and chronic setting, emphasizing contemporary approaches and evolving data on the relevance of dietary restriction and the use of novel potassium binders.

Renin–angiotensin–aldosterone system inhibitors (RAASi) and mineralocorticoid receptor antagonists (MRAs) are important interventions to improve outcomes in patients with chronic kidney disease and heart failure, but their use is limited in some patients by the development of hyperkalemia. The risk of hyperkalemia may differ between agents, with one trial showing lower risk of hyperkalemia with the novel non-steroidal MRA finerenone compared with steroidal MRA spironolactone. Novel potassium binders, including patiromer and sodium zirconium cyclosilicate, are available interventions to manage hyperkalemia and enable continuation of RAASi and MRAs in patients who could benefit from these treatments. These agents bind free potassium ions in the lumen of the gastrointestinal tract to prevent the absorption of dietary potassium and increase potassium secretion. Several studies showed that potassium binders are effective compared with placebo for preventing hyperkalemia or steroidal MRA discontinuation, but none has evaluated whether this strategy impacts clinically important endpoints such as cardiovascular events. Due to this and other limitations related to cost, clinical availability, pill burden and patient selection, alternative potential strategies to mitigate hyperkalemia may be more practical. Conservative strategies include increased monitoring and use of loop or thiazide diuretics to increase urinary potassium excretion. Non-steroidal MRAs may have a lower risk of hyperkalemia than steroidal MRAs and have stronger anti-inflammatory and anti-fibrotic effects with resultant reduced risk of kidney disease progression. Sodium-glucose cotransporter-2 inhibitors also decrease hyperkalemia risk in patients on MRAs and decrease cardiovascular events and kidney disease progression. These may be better first-line interventions to obviate the need for potassium binders and offer additional benefits. [ABSTRACT FROM AUTHOR]

Sodium Zirconium Cyclosilicate (SZC) is commonly used for treating hyperkalemia because it sequesters gastrointestinal potassium ions, thereby reducing serum potassium levels. However, a less-discussed aspect of SZC is its radiopacity on x-ray-based imaging techniques. The European Medicines Agency (EMA) has only vaguely addressed this issue. Radiopaque substances like SZC can interfere with diagnostic imaging, creating challenges for clinicians and radiologists. We present the case of a 34-year-old Italian male to illustrate these concerns. [ABSTRACT FROM AUTHOR]

BackgroundReliable, timely-onset, oral treatments with an acceptable safety profile for patients with hyperkalemia are needed. We examined the efficacy and safety of sodium zirconium cyclosilicate (SZC; formerly ZS-9) treatment for ≤ 48 h in patients with baseline serum potassium level ≥ 5.5 mmol/L.MethodsData were pooled from two phase 3 studies (ZS-003 and HARMONIZE) among patients receiving SZC 10 g three times daily. Outcomes included mean and absolute change from baseline, median time to potassium level ≤ 5.5 and ≤ 5.0 mmol/L, and proportion achieving potassium level ≤ 5.5 and ≤ 5.0 mmol/L at 4, 24, and 48 h. Outcomes were stratified by baseline potassium. Safety outcomes were evaluated.ResultsAt baseline, 125 of 170 patients (73.5%) had potassium level 5.5- 6.5 mmol/L. Regardless of baseline potassium, mean potassium decreased at 1 h post-initial dose. By 4 and 48 h, 37.5% and 85.0% of patients achieved potassium level ≤ 5.0 mmol/L, respectively. Median (95% confidence interval) times to potassium level ≤ 5.5 and ≤ 5.0 mmol/L were 2.0 (1.1-2.0) and 21.6 (4.1-22.4) h, respectively. Fifteen patients (8.8%) experienced adverse events; none were serious.ConclusionsSZC 10 g three times daily achieved serum potassium reduction and normokalemia, with a favorable safety profile.Trial registrationClinicalTrials.gov identifiers: ZS-003: NCT01737697 and HARMONIZE: NCT02088073.

This correction notice addresses an error in the affiliation of one of the authors in a study on the effectiveness and safety of sodium zirconium cyclosilicate in Chinese patients with hyperkalemia. The correction does not impact the scientific conclusions of the article. The study involves a multicenter, real-world analysis of the treatment patterns in the Chinese population. The authors emphasize that the views expressed in the article are their own and may not reflect those of their affiliated organizations or the publisher. [Extracted from the article]

The document is a corrigendum for a study on the effectiveness, safety, and treatment pattern of sodium zirconium cyclosilicate in Chinese patients with hyperkalemia. The study is a multicenter, prospective, real-world analysis conducted in various hospitals across China. The article corrects an error in one of the affiliations listed in the original publication, emphasizing that the scientific conclusions remain unchanged. [Extracted from the article]

Aims: Several patients with heart failure and reduced ejection fraction (HFrEF) do not receive renin–angiotensin–aldosterone system (RAAS) inhibitors at the recommended dose or at all, frequently due to actual or feared hyperkalaemia. Sodium zirconium cyclosilicate (SZC) is an orally administered non‐absorbed intestinal potassium binder proven to lower serum potassium concentrations. Methods and results: PRIORITIZE‐HF was an international, multicentre, parallel‐group, randomized, double‐blind, placebo‐controlled study to evaluate the benefits and risks of using SZC to intensify RAAS inhibitor therapy. Patients with symptomatic HFrEF were eligible and randomly assigned to receive SZC 5 g or placebo once daily for 12 weeks. Doses of study medication and RAAS inhibitors were titrated during the treatment period. The primary endpoint was the proportion of patients at 12 weeks in the following categories: (i) any RAAS inhibitor at less than target dose, and no MRA; (ii) any RAAS inhibitor at target dose and no MRA; (ii) MRA at less than target dose; and (iv) MRA at target dose. Due to challenges in participant management related to the COVID‐19 pandemic, the study was prematurely terminated with 182 randomized patients. There was no statistically significant difference in the distribution of patients by RAAS inhibitor treatment categories at 3 months (P = 0.43). The proportion of patients at target MRA dose was numerically higher in the SZC group (56.4%) compared with the placebo group (47.0%). Overall, SZC was well tolerated. Conclusions: PRIORITIZE‐HF was terminated prematurely due to COVID‐19 and did not demonstrate a statistically significant increase in the intensity of RAAS inhibitor therapies with the potassium‐reducing agent SZC compared with placebo. [ABSTRACT FROM AUTHOR]