Sodium Zirconium Research Articles

Coste-efectividad del ciclosilicato de sodio y zirconio para el tratamiento de la hiperpotasemia en pacientes con enfermedad renal crónica o insuficiencia cardiaca en España

Background and objectiveHyperkalemia (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 methodsTwo 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. ResultsSZC 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. ConclusionsSZC 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.

Consensus statement on the management of hyperkalaemia-An Asia-Pacific perspective.

Hyperkalaemia is an electrolyte imbalance that impairs muscle function and myocardial excitability, and can potentially lead to fatal arrhythmias and sudden cardiac death. The prevalence of hyperkalaemia is estimated to be 6%-7% worldwide and 7%-10% in Asia. Hyperkalaemia frequently affects patients with chronic kidney disease, heart failure, and diabetes mellitus, particularly those receiving treatment with renin-angiotensin-aldosterone system (RAAS) inhibitors. Both hyperkalaemia and interruption of RAAS inhibitor therapy are associated with increased risks for cardiovascular events, hospitalisations, and death, highlighting a clinical dilemma in high-risk patients. Conventional potassium-binding resins are widely used for the treatment of hyperkalaemia; however, caveats such as the unpalatable taste and the risk of gastrointestinal side effects limit their chronic use. Recent evidence suggests that, with a rapid onset of action and improved gastrointestinal tolerability, novel oral potassium binders (e.g., patiromer and sodium zirconium cyclosilicate) are alternative treatment options for both acute and chronic hyperkalaemia. To optimise the care for patients with hyperkalaemia in the Asia-Pacific region, a multidisciplinary expert panel was convened to review published literature, share clinical experiences, and ultimately formulate 25 consensus statements, covering three clinical areas: (i) risk factors of hyperkalaemia and risk stratification in susceptible patients; (ii) prevention of hyperkalaemia for at-risk individuals; and (iii) correction of hyperkalaemia for at-risk individuals with cardiorenal disease. These statements were expected to serve as useful guidance in the management of hyperkalaemia for health care providers in the region.

Cost-effectiveness analysis of sodium zirconium cyclosilicate for hyperkalemia among patients with chronic kidney disease or heart failure in Kuwait

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.

Randomised, blinded, cross-over evaluation of the palatability of and preference for different potassium binders in participants with chronic hyperkalaemia in the USA, Canada and Europe: the APPETIZE study

ObjectivesTraditional potassium (K+) binders for treating hyperkalaemia are unpalatable and poorly tolerated. Newer K+ binders are reportedly better tolerated; however, no published data describe their palatability, a determinant of long-term...

Mortality and hyperkalaemia-associated hospitalisation in patients with chronic kidney disease: comparison of sodium zirconium cyclosilicate and sodium/calcium polystyrene sulfonate.

Sodium zirconium cyclosilicate (SZC), a novel drug used for treating hyperkalaemia, is effective in reducing serum potassium levels. The effects of potassium adsorbents on the mortality and hyperkalaemia-associated hospitalisation rates remain unclear. We aimed to examine how mortality and hyperkalaemia-associated hospitalisation rates vary with usage of various potassium adsorbents. This retrospective study used patients' data between April 2008 and August 2021 obtained from a large-scale Japanese medical claims database. Consecutive patients with chronic kidney disease (CKD) prescribed potassium adsorbents were enrolled and divided into three groups according to the adsorbent type [SZC, calcium polystyrene sulfonate (CPS), and sodium polystyrene sulfonate (SPS)] and were observed for 1 year. The primary outcome was a composite of mortality and hyperkalaemia-associated hospitalisation. In total, 234, 54 183, and 18 692 patients were prescribed SZC, CPS, and SPS, respectively. The SZC group showed a higher event-free survival rate than the other two groups. The hazard ratio for the primary outcome in the CPS and SPS groups was similar in the analyses of the subgroups of patients who did not receive renal replacement therapy and those who received haemodialysis. The SZC group had a higher renin-angiotensin-aldosterone system inhibitors (RAASi) continuation rate compared to CPS and SPS groups, the difference being especially significant for SPS. This real-world study demonstrated the therapeutic effect of SZC in reducing mortality and hyperkalaemia-associated hospitalisations. The high RAASi continuation rate in the SZC group might be a contributing factor for improvement of the primary outcome.

Hyperkalaemia in Cardiological Patients: New Solutions for an Old Problem.

Hyperkalaemia is one of the most common electrolyte disorders in patients with cardiovascular disease (CVD). The true burden of hyperkalaemia in the real-world setting can be difficult to assess, but in population-based cohort studies up to 4 in 10 patients developed hyperkalaemia. In addition to drugs interfering with potassium metabolism and food intake, several conditions can cause or worsen hyperkalaemia, such as advanced age, diabetes, and chronic kidney disease. Mortality, cardiovascular morbidity, and hospitalisation are higher in patients with hyperkalaemia. Hyperkalaemia represents a major contraindication or a withholding cause for disease-modifying therapies like renin-angiotensin-aldosterone inhibitors (RAASi), mainly mineralocorticoid receptor antagonists. Hyperkalaemia can be also classified as acute and chronic, according to the onset. Acute hyperkalaemia is often a life-threatening emergency requiring immediate treatment to avoid lethal arrhythmias. Therapy goal is cell membrane stabilisation by calcium administration, cellular intake, shift of extracellular potassium to the intracellular space (insulin, beta-adrenergic agents, sodium bicarbonate), and increased elimination with diuretics or dialysis. Chronic hyperkalaemia was often managed with dietary counselling to prevent potassium-rich food intake and tapering of potassium-increasing drugs, mostly RAASi. Sodium polystyrene sulphonate, a potassium binder, was the only therapeutic option. Recently, new drugs such as patiromer and sodium zirconium cyclosilicate give new opportunities for the treatment of hyperkalaemia, as they proved to be safe, well tolerated, and effective. Aim of this review is to describe the burden of hyperkalaemia in cardiovascular patients, its direct and indirect effects, and the therapeutic options now available in the acute and chronic setting.

Hyperkalemia: Pharmacotherapies and Clinical Considerations.

Hyperkalemia has been defined as a condition where a serum potassium level is >5.5 mmol/l. It is associated with fatal dysrhythmias and muscular dysfunction. Certain medical conditions, such as chronic kidney disease (CKD), diabetes mellitus, and others, can lead to hyperkalemia. Many of the signs of hyperkalemia are nonspecific. A history and physical examination can be beneficial in the diagnosis of the condition. In this regard, certain characteristic electrocardiogram findings are associated with hyperkalemia along with laboratory potassium levels. In acute and potentially lethal conditions, hyperkalemia treatments include glucose and insulin, bicarbonate, calcium gluconate, beta-2 agonists, hyperventilation, and dialysis. There are several drugs, both old and new, that can additionally aid in the reduction of serum potassium levels. The present investigation evaluated some of these different drugs, including sodium polystyrene sulfonate (SPS), sodium zirconium cyclosilicate (SZC), and patiromer. These drugs each have increased selectivity for potassium and work primarily in the gastrointestinal (GI) tract. Each of these medications has unique benefits and contraindications. Clinicians must be aware of these medications when managing patients with hyperkalemia.

Evaluation of the introduction of novel potassium binders in routine care; the Stockholm CREAtinine measurements (SCREAM) project

BackgroundThe pharmacological management of hyperkalemia traditionally considered calcium or sodium polystyrene sulfonate and, since recently, the novel binders patiromer and sodium zirconium cyclosilicate. We evaluated their patterns of use, duration of treatment and relative effectiveness/safety in Swedish routine care.MethodsObservational study of adults initiating therapy with sodium polystyrene sulfonate or a novel binder (sodium zirconium cyclosilicate or patiromer) in Stockholm 2019–2021. We quantified treatment duration by repeated dispensations, compared mean achieved potassium concentration within 60 days, and potential adverse events between treatments.ResultsA total of 1879 adults started treatment with sodium polystyrene sulfonate, and 147 with novel binders (n = 41 patiromer and n = 106 sodium zirconium cyclosilicate). Potassium at baseline for all treatments was 5.7 mmol/L. Sodium polystyrene sulfonate patients stayed on treatment a mean of 61 days (14% filled ≥3 consecutive prescriptions) compared to 109 days on treatment (49% filled ≥3 prescriptions) for novel binders. After 15 days of treatment, potassium similarly decreased to 4.6 (SD 0.6) and 4.8 (SD 0.6) mmol/L in the sodium polystyrene sulfonate and novel binder groups, respectively, and was maintained over the 60 days post-treatment. In multivariable regression, the odds ratio for novel binders (vs sodium polystyrene sulfonate) in reaching potassium ≤ 5.0 mmol/L after 15 days was 0.65 (95% CI 0.38–1.10) and after 60 days 0.89 (95% CI 0.45–1.76). Hypocalcemia, hypokalemia, and initiation of anti-diarrheal/constipation medications were the most-commonly detected adverse events. In multivariable analyses, the OR for these events did not differ between groups.ConclusionWe observed similar short-term effectiveness and safety for all potassium binders. However, treatment duration was longer for novel binders than for sodium polystyrene sulfonate.Graphical abstract

Effects of Patiromer and Sodium Zirconium Cyclosilicate on Blood Pressure in Rats with Chronic Kidney Disease.

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. 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. 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). 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.

Effectiveness, safety, and treatment pattern of sodium zirconium cyclosilicate in Chinese patients with hyperkalemia: interim analysis from a multicenter, prospective, real-world study (Actualize Study).

Introduction: Sodium zirconium cyclosilicate (SZC) is a nonabsorbed cation-exchanger approved in China for the treatment of hyperkalemia [HK; serum potassium (sK+) levels >5.0mmol/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 ≥18years with documented HK within 1-year before study enrollment day. These patients were followed up for 6months 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 5.9mmol/L to 5.0mmol/L after the correction phase. For the maintenance phase, the mean sK+ levels were maintained at 5.2mmol/L and 5.0mmol/L in the FAS-P2 new and ongoing user, respectively, and 5.3mmol/L in the FAS-H subgroup. A considerable proportion of patients showed normokalemia after 48h of SZC treatment (FAS-P1:51.3%) which was maintained up to 6months 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.

Management of hyperkalemia: Expert consensus from Kuwait - a Modified Delphi Approach.

Hyperkalemia is common in heart failure (HF) patients on renin angiotensin aldosterone inhibitors (RAASi), in chronic kidney disease (CKD), and in hemodialysis, and it negatively impacts their management. New potassium binders, such as sodium zirconium cyclosilicate (SZC), are effective in management of acute and chronic hyperkalemia. However, guidelines inconsistencies and lack of standardized treatment protocols are hindering proper and wider use of such agents. Therefore, an expert panel from Kuwait developed a consensus statement to address hyperkalemia management in acute settings, in HF, in CKD, and in hemodialysis. A three-step modified Delphi method was adopted to develop the present consensus, which consisted of two rounds of voting and in-between a virtual meeting. Twelve experts from Kuwait participated in this consensus. Statements were developed and shared with experts for voting. A meeting was held to discuss statements that did not reach consensus at the first round and then the remaining statements were shared for final voting. The consensus consists of 44 statements involving an introduction to and the management of hyperkalemia in acute settings, HF, CKD, and hemodialysis. Thirty-six statements approved unanimously in the first vote. In the second vote, four statements were removed and four were approved after editing. Hyperkalemia management lacks standardized definitions, treatment thresholds and consistent guidelines and laboratory practices. This consensus is in response to lack of standardized treatment in the Arabian Gulf, and it aims to establish guidance on hyperkalemia management for healthcare practitioners in Kuwait and highlight future needs.

Cost-effectiveness analysis of sodium zirconium cyclosilicate for treating hyperkalemia among Chinese patients.

Hyperkalemia 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. Individual 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. In 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. SZC 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.

Potassium homeostasis and therapeutic intervention with sodium zirconium cyclosilicate: A model-informed drug development case study.

Potassium (K+ ) is the main intracellular cation in the body. Elevated K+ levels (hyperkalemia) increase the risk of life-threatening arrhythmias and sudden cardiac death. However, the details of K+ homeostasis and the effects of orally administered K+ binders, such as sodium zirconium cyclosilicate (SZC), on K+ redistribution and excretion in patients remain incompletely understood. We built a fit-for-purpose systems pharmacology model to describe K+ homeostasis in hyperkalemic subjects and capture serum K+ (sK+ ) dynamics in response to acute and chronic administration of SZC. The resulting model describes K+ distribution in the gastrointestinal (GI) tract, blood, and extracellular and intracellular spaces of tissue, renal clearance of K+ , and K+ -SZC binding and excretion in the GI tract. The model, which was fit to time-course sK+ data for individual patients from two clinical trials, accounts for bolus delivery of K+ in meals and oral doses of SZC. The virtual population of patients derived from fitting the model to these trials was then modified to predict the SZC dose-response and inform clinical trial design in two new applications: emergency lowering of sK+ in severe hyperkalemia and prevention of hyperkalemia between dialysis sessions in patients with end-stage chronic kidney disease. In both cases, the model provided novel and useful insight that was borne out by the now completed clinical trials, providing a concrete case study of fit-for-purpose, model-informed drug development after initial approval of a drug.

CO35 Clinical Outcomes Associated with Sodium Zirconium Cyclosilicate for Treating Hyperkalaemia in Patients Receiving Haemodialysis

CO35 Clinical Outcomes Associated with Sodium Zirconium Cyclosilicate for Treating Hyperkalaemia in Patients Receiving Haemodialysis

Plant-based diet in chronic kidney disease through the use of sodium zirconium cyclosilicate (Helpful trial)

Plant-based diet in chronic kidney disease through the use of sodium zirconium cyclosilicate (Helpful trial)

The efficacy and safety of new potassium binders on renin-angiotensin-aldosterone system inhibitor optimization in heart failure patients: a systematic review and meta-analysis.

Guideline-directed medical therapy (GDMT) has improved outcomes in patients with heart failure, including the use of renin-angiotensin-aldosterone system inhibitors, which can hinder the excretion of potassium, resulting in hyperkalaemia. New potassium binders (NPBs) can prevent this adverse effect; however, the efficacy and safety of NPB for this indication have not been fully established. We conducted a systematic review and meta-analysis synthesizing randomized controlled trials (RCTs), which were retrieved by systematically searching PubMed, Web of Science, Scopus, and Cochrane through 26 April 2023. The risk of bias assessment was conducted, following Cochrane's updated Risk of Bias 2 assessment tool. We used the fixed-effects model to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD), with a 95% confidence interval (CI) (PROSPERO ID: CRD42023426113). We included six RCTs with a total of 1432 patients. NPB was significantly associated with successful mineralocorticoid receptor antagonist (MRA) optimization [RR: 1.13 with 95% CI (1.02-1.25), P=0.02], decreased patients with MRA at less than the target dose [RR: 0.72 with 95% CI (0.57-0.90), P=0.004], and decreased hyperkalaemic episodes [RR: 0.42 with 95% CI (0.24-0.72), P=0.002]. However, there was no difference between NPB and placebo regarding angiotensin-converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB)/angiotensin receptor/neprilysin inhibitor (ANRi) optimization [RR: 1.02 with 95% CI (0.89-1.17), P=0.76] and serum potassium change [MD: -0.31 with 95% CI (-0.61 to 0.00), P=0.05], with an acceptable safety profile except for the increased incidence of hypokalaemia with NPB [RR: 1.57 with 95% CI (1.12-2.21), P=0.009]. NPB has been shown to improve GDMT outcomes by enhancing MRA optimization and reducing hyperkalaemic episodes. However, there are limited data on the effects of NPB on ACEi/ARB/ANRi optimization. Future RCTs should investigate ACEi/ARB/ANRi optimization and conduct head-to-head comparisons of NPB (patiromer and sodium zirconium cyclosilicate).

Sodium zirconium cyclosilicate hydrate reduces medical expenses compared with hemodialysis in patients with acute hyperkalemia

BackgroundSodium zirconium cyclosilicate (SZC) has recently emerged as a therapeutic option for the management of acute hyperkalemia. Nevertheless, the relative effectiveness, safety, and financial considerations of SZC therapy versus conventional hemodialysis therapy remain uncertain.MethodsIn this retrospective study, we embarked upon a comparative analysis encompassing the financial aspects, safety profiles, and efficacy metrics associated with SZC therapy and hemodialysis in patients grappling with acute hyperkalemia. No patients had systemic congestion or uremia.ResultsA total of 21 patients (median 81 years old, 14 men) were included; 14 received SZC therapy and seven underwent hemodialysis. Acute hyperkalemia improved immediately within several days without any procedure-related adverse events, regardless of therapeutic interventions (p < 0.05 for both). Total medical expenses were significantly lower in the SZC group than in the hemodialysis group (55,596 [43,652, 69,761] vs. 419,768 [354,270, 514,700] Japanese yen, p < 0.001).ConclusionsIn the realm of acute hyperkalemia management, SZC therapy emerges as an economically judicious alternative, while upholding parity in terms of safety and effectiveness when compared with the conventional hemodialysis paradigm—unless complicated by systemic congestion or uremia. The pressing task at hand revolves around the discernment of the optimal patient demographic for SZC therapy within the ambit of acute hyperkalemia.

Effectiveness of Patiromer Versus Sodium Zirconium Cyclosilicate for the Management of Acute Hyperkalemia.

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. 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. 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. 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. 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 13944: The Efficacy and Safety of New Potassium Binders on RASSi Optimization in Hyperkalemic Patients With Heart Failure: A Systematic-Review and Meta-Analysis of Randomized Controlled Trials

Introduction: Guideline-directed medical therapy (GDMT) has improved outcomes in patients with heart failure (HF), including the use of renin-angiotensin-aldosterone system inhibitors (RAASi); angiotensin-converting enzyme inhibitors (ACEis), angiotensin receptor blockers (ARBs), angiotensin receptor/neprilysin inhibitor (ANRi), and mineralocorticoid receptor antagonists (MRAs). RAASi can hinder the excretion of potassium, resulting in hyperkalemia. New potassium binders (NPB) (patiromer and sodium zirconium cyclosilicate) can prevent this adverse effect; however, the efficacy and safety of NPB for this indication have not been fully established. Methods: We conducted a systematic review and meta-analysis synthesizing randomized controlled trials (RCTs), which were retrieved by systematically searching: PubMed, Web of Science, SCOPUS, and Cochrane through April 26th, 2023. We used the fixed-effect model to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD), with a 95% confidence interval (CI). Results: We included five RCTs with a total of 1,399 patients. BPB was significantly associated with successful MRA optimization (RR: 1.13 with 95% CI [1.02, 1.25], P=0.02), decreased patients with MRA at less than target dose (RR: 0.72 with 95% CI [0.57, 0.90], P=0.004), and decreased hyperkalemic episodes (RR: 0.50 with 95% CI [0.32, 0.79], P=0.003). However, there was no difference between NPB and placebo regarding ACEi/ARB/ANRi optimization (RR: 1.02 with 95% CI [0.89, 1.17], P=0.76) and serum potassium change (MD: -0.31 with 95% CI [-0.61, 0.00], P=0.05). Conclusion: NPB can successfully improve GDMT outcomes by enhancing MRA optimization and decreasing hyperkalemic episodes. However, data regarding the NPB effect on ACEi/ARB/ANRi optimization remain scarce. Therefore, future RCTs should investigate it and conduct a head-to-head comparison of NPB.

Effect of sodium zirconium cyclosilicate in combination with insulin and glucose infusion on hyperkalemia treatment

Purpose: To evaluate the efficacy of sodium zirconium cyclosilicate (SZC) in combination with insulinand glucose infusion in managing hyperkalemia.&#x0D; 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.&#x0D; Results: Post-treatment, the potassium levels in all three groups exhibited a significant reduction when compared to pre- treatment values (p &lt; 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.&#x0D; 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.