Zirconium Cyclosilicate Research Articles

P330 MANAGEMENT OF HYPERKALEMIA IN A PATIENT WITH HFREF

Abstract Hyperkalimia (HK) is a condition that occurs very frequently in patients with heart failure (HF). HK often limits and discourages the implementation and optimization of RAASI therapy in patients with HFrEF. The introduction of the new K–binders drugs has made it possible to overcome this obstacle by allowing optimization of therapy even in patients with persistent hyperkalemia. Mr. AB aged 83 years cognitively intact and autonomous ( Katz‘s BADL and Lawton‘s IADL preserved; MMSE 29/30). February 2022 accessed DEA for aggravating exertional dyspnea; at that time echocardiogram finding reduced left ventricular systolic function, FE 35%. March 2022 performed elective coronarography: coronary tree free of critical lesions, confirmed on echocardiogram reduced FE. Post indication to undertake Sacubitril/Valsartan, beta blocker and SGLT2i therapy. For moderate CKD (eGFR 33 ml/min) with tendency to hyperkalemia not initiated MRA. April 2022 the patient was taken to our Heart Failure Outpatient Clinic–UTIG– AOU Careggi. June 2022 considered improvement in renal function and Kaliemia in optimized range GDMTs therapy with Potassium Canreonate 25 mg/day. At control EEs in July 2022 found hyperKalemia with K values 5.5 mEq/L but stability of renal function. Reduced therefore the dosage of Potassium Canreonate (25 mg every other day) with indication to repeat blood tests soon. September 2022 despite reduction in MRA dosage further increase in Kaliemia values to 5.8 mEq/L. Suspended Potassium Canreonate and started Sodium Zirconium Cyclosilicate therapy initially at loading dosage of 10 g three times daily for two days then continued with maintenance dosage of 5 g. At follow–up performed the following week K 4.5 mEq/L. Re–introduced Potassium Canreonate 25 mg/day with initial tight control of potassium values that remained stably at optimal values. Hyperkalemia is an obstacle in titrating HFrEF, especially in elderly patients with CKD. However, we have new drugs available that may allow the implementation of guideline–recommended treatments by controlling potassium values.

Real-World Modifications of Renin-Angiotensin-Aldosterone System Inhibitors in Patients with Hyperkalemia Initiating Sodium Zirconium Cyclosilicate Therapy: The OPTIMIZE I Study.

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. Adults (≥ 18years) 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. A total of 589 patients initiated SZC during RAASi therapy (mean age 61.0years, 65.2% male), and 82.7% patients (n = 487) kept RAASi after index (mean follow-up = 8.1months). 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 < 0.05) and fewer prior emergency department (ED) visits (0.78 [0.63-0.96]; p < 0.05). Consistent with clinical trial findings, nearly 80% of patients who initiated SZC for HK optimized their RAASi therapy. Patients may require long-term SZC therapy to encourage continuation of RAASi therapy especially after inpatient and ED visits.

Safety and efficacy of new potassium binders on hyperkalemia management in patients with heart failure: a systematic review and meta-analysis of randomized controlled trials.

Hyperkalemia leads to suboptimal use of evidence-based therapies in patients with heart failure (HF). Therefore, we aimed to assess whether new potassium binders are effective and safe to promote medical optimization in patients with HF. MEDLINE, Cochrane, and Embase were searched for randomized controlled trials (RCTs) that reported outcomes after initiation of Patiromer or Sodium Zirconium Cyclosilicate (SZC) versus placebo in patients with HF at high risk of hyperkalemia development. Risk ratios (RR) with 95% confidence intervals (CI) were pooled with a random effects model. Quality assessment and risk of bias were performed according to Cochrane recommendations. A total of 1432 patients from 6 RCTs were included, of whom 737 (51.5%) patients received potassium binders. In patients with HF, potassium binders increased the use of renin-angiotensin-aldosterone inhibitors (RR 1.14; 95% CI 1.02-1.28; p = 0.021; I2 = 44%) and reduced the risk of hyperkalemia (RR 0.66; 95% CI 0.52-0.84; p < 0.001; I2 = 46%). The risk of hypokalemia was significantly increased in patients treated with potassium binders (RR 5.61; 95% CI 1.49-21.08; p = 0.011; I2 = 0%). There was no difference between groups in all-cause mortality rates (RR 1.13; 95% CI 0.59-2.16; p = 0.721; I2 = 0%) or in adverse events leading to drug discontinuation (RR 1.08; 95% CI 0.60-1.93; p = 0.801; I2 = 0%). The use of new potassium binders Patiromer or SZC in patients with HF at risk for hyperkalemia increased the rates of medical therapy optimization with renin-angiotensin-aldosterone inhibitors and reduced the incidence of hyperkalemia, at the cost of an increased prevalence of hypokalemia.

Evaluation of the effect of sodium zirconium cyclosilicate on arrhythmia-related cardiovascular outcomes in patients receiving chronic haemodialysis with hyperkalaemia: protocol for the multicentre, randomised, controlled DIALIZE-Outcomes study

IntroductionPatients with kidney failure receiving chronic haemodialysis have elevated risk of arrhythmias potentially increasing the likelihood of sudden cardiac death, stroke and hospitalisation. The DIALIZE study (NCT03303521) demonstrated that sodium...

In pursuit of balance: renin-angiotensin-aldosterone system inhibitors and hyperkalaemia treatment.

Hyperkalaemia is a life-threatening condition leading to significant morbidity and mortality. It is common in heart failure (HF) patients due to the disease itself, which often co-exists with chronic kidney disease and diabetes mellitus, the fluctuations in renal function, and the use of some drugs [i.e. renin-angiotensin-aldosterone system (RAAS) inhibitors]. In particular, hyperkalaemia opposes to their administration or up-titration, thus impacting on mortality. New K+ binders, namely, patiromer and sodium zirconium cyclosilicate, are an intriguing option to manage hyperkalaemia in HF patients, both to reduce its fatal effects and to let clinicians up-titrate RAAS inhibitors. Even if their real impact on strong outcomes is still to be determined, we hereby provide an overview of hyperkalaemia in HF and its current management. New trials are welcome to fill the gap in knowledge.

Sodium polystyrene is unsafe and should not be prescribed for the treatment of hyperkalaemia: primum non nocere!

'Old-generation' potassium (K) binders [i.e. sodium (SPS) and calcium polystyrene sulfonate] are widely used, but with substantial heterogeneity across countries to treat hyperkalaemia (HK). However, there are no randomized data to support their chronic use to manage HK, nor have they been shown to have a renin-angiotensin-aldosterone system inhibitor (RAASi)-enabling effect. These compounds have poor tolerability and an unpredictable onset of action and magnitude of K lowering. Furthermore, SPS may induce fluid overload, owing to the fact that it exchanges K for sodium. Its use has also been associated with colonic necrosis, as emphasized by a black box warning from the US Food and Drug Administration. In contrast, two new K binders, patiromer and sodium zirconium cyclosilicate, have been shown to be safe and well tolerated for chronic management of HK, thereby enabling RAASi optimization, as acknowledged by the latest international cardiorenal guidelines. In view of the lack of reliable evidence regarding the efficacy and safety of the old-generation K binders compared with the placebo-controlled randomized and real-word evidence demonstrating the safety, efficacy and RAASi-enabling effect of the new K binders, clinicians should now use these new K binders to treat HK (primum non nocere!).

Pharmacological strategies to manage hyperkalaemia: out with the old, in with the new? Not so fast….

Since the 1950s, sodium polystyrene sulphonate (SPS) has been the dominant cation exchange agent prescribed for hyperkalaemia. Clinicians have had plenty of time to learn of SPS's advantages and limitations. The demands of drug regulatory agencies regarding the incorporation of medications into the market were not so stringent then as they are today, and the efficacy and safety of SPS have been questioned. In recent years, two novel cation exchangers, patiromer and sodium zirconium cyclosilicate, have received (or are in the process of receiving) regulatory approval in multiple jurisdictions globally, after scrutiny of carefully conducted trials regarding their short-term and mid-term efficacy. In this debate, we defend the view that all three agents are likely to have similar efficacy. Harms are much better understood for SPS than for newer agents, but currently there are no data to suggest that novel agents are safer than SPS. Drug choices need to consider costs, access and numbers-needed-to-treat to prevent clinically important events; for potassium exchangers, we need trials directly examining clinically important events.

Fecal Ammonium in mice with CKD: gastrointestinal sequestration by SZC.

Background: Urinary Ammonium (NH4+) excretion is decreased in CKD but very little is known about fecal NH4+excretion. Sodium Zirconium Cyclosilicate (SZC) is a cation-exchanger that selectively captures K+ in the gastrointestinal tract. We investigated if SZC can sequester NH4+ in vivo and evaluated the effect of SZC on fecal NH4+ in a mouse model of CKD. Methods: Mice with CKD induced by 5/6 kidney ablation were fed either a regular diet or a diet containing SZC (4g/Kg) and followed for 7 days. Feces NH4+ was measured before and after addition of 50 mEq KCl/L to release NH4+ from SZC. NH4+ sequestered in SZC in the gastrointestinal tract was estimated from the delta fecal NH4+observed when KCl was added to liberate the sequestered NH4+. Results: In mice with CKD fecal NH4+ excretion was higher than in normal mice and also higher than urine NH4+ excretion measured concurrently. Using data pooled from the SZC diet, the delta NH4+ was 6.5 ± 0.6 as compared to 0.6 ± 0.6 µmol/g on the normal diet p<0.0001. Conclusions:Fecal NH4+ excretion in CKD is increased and about 6-fold higher than urine NH4+ excretion revealing an important route of elimination of NH4+ present in the GI tract. SZC administration sequesters a substantial portion of NH4+ in the GI tract suggesting that the binding of NH4+ offers therapeutic potential beyond its known primary action as a specific K+ binder.

A randomized study to compare oral potassium binders in the treatment of acute hyperkalemia

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.

Delivery of sodium zirconium cyclosilicate through gastric and enteral feeding tubes.

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Rationale and design of CONTINUITY: a Phase 4 randomized controlled trial of continued post-discharge sodium zirconium cyclosilicate treatment versus standard of care for hyperkalemia in chronic kidney disease.

Individuals with chronic kidney disease (CKD) hospitalized with hyperkalemia are at risk of hyperkalemia recurrence and re-hospitalization. We present the rationale and design of CONTINUITY, a study to examine the efficacy of continuing sodium zirconium cyclosilicate (SZC)-an oral, highly selective potassium (K+) binder-compared with standard of care (SoC) on maintaining normokalemia and reducing re-hospitalization and resource utilization among participants with CKD hospitalized with hyperkalemia. This Phase 4, randomized, open-label, multicenter study will enroll adults with Stage 3b-5 CKD and/or estimated glomerular filtration rate <45mL/min/1.73 m2, within 3months of eligibility screening, hospitalized with a serum potassium (sK+) level of >5.0-≤6.5 mmol/L, without ongoing K+ binder treatment. The study will include an in-hospital phase, where participants receive SZC for 2-21days, and an outpatient (post-discharge) phase. At discharge, participants with sK+ 3.5-5.0mmol/L will be randomized (1:1) to SZC or SoC and monitored for 180days. The primary endpoint is the occurrence of normokalemia at 180days. Secondary outcomes include incidence and number of hospital admissions or emergency department visits both with hyperkalemia as a contributing factor, and renin-angiotensin-aldosterone system inhibitor down-titration. The safety and tolerability of SZC will be evaluated.Ethics approval has been received from all relevant ethics committees. Enrollment started March 2022 and the estimated study end date is December 2023. This study will assess the potential of SZC versus SoC in managing people with CKD and hyperkalemia post-discharge. ClinicalTrials.gov identifier: NCT05347693; EudraCT: 2021-003527-14, registered on 19 October 2021.

Compared effectiveness of sodium zirconium cyclosilicate and calcium polystyrene sulfonate on hyperkalemia in patients with chronic kidney disease.

Hyperkalemia is a well-recognized electrolyte abnormality in patients with chronic kidney disease (CKD). Potassium binders are often used to prevent and treat hyperkalemia. However, few studies have evaluated the difference in serum potassium (K+) level-lowering effect during the post-acute phase between the novel potassium binder, sodium zirconium cyclosilicate (ZSC), and conventional agents. This retrospective study included patients who received potassium binders (either ZSC or calcium polystyrene sulfonate [CPS]) in our hospital between May 2020 and July 2022. The patients were divided into the ZSC and CPS groups. After propensity score matching, we compared changes from baseline to the first follow-up point, at least 4 weeks after initiating potassium binders, in electrolytes including K+ level between the two groups. Of the 132 patients, ZSC and CPS were administered in 48 and 84 patients, respectively. After matching, 38 patients were allocated to each group. The ZSC group showed greater reduction in K+ levels than did the CPS group (P < 0.05). Moreover, a significant increase in serum sodium minus chloride levels, a surrogate marker for metabolic acidosis, was observed in the ZSC group (P < 0.05). Our results demonstrated that ZSC could potentially improve hyperkalemia and metabolic acidosis in patients with CKD.

Use of tecovirimat for mpox infection followed by JYNNEOS vaccination postinfection in a liver transplant recipient.

Use of tecovirimat for mpox infection followed by JYNNEOS vaccination postinfection in a liver transplant recipient.

Evaluation of safety, effectiveness and treatment patterns of sodium zirconium cyclosilicate in management of hyperkalaemia in China: a real-world study protocol

IntroductionHyperkalaemia (HK) is a potentially life-threatening electrolyte imbalance associated with several adverse clinical outcomes. The efficacy and negative effects of currently existing treatment options have made HK management questionable. Sodium...

Single Dose of Sodium Zirconium Cyclosilicate Versus Sodium Polystyrene Sulfonate in Hospitalized Patients With Hyperkalemia.

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. 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. 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. 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. 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.

Impact on hospitalizations of long-term versus short-term therapy with sodium zirconium cyclosilicate during routine outpatient care of patients with hyperkalemia: the recognize I study

ABSTRACT Background Hyperkalemia is associated with increased healthcare resource utilization (HRU). This study evaluated the impact of sodium zirconium cyclosilicate (SZC) use on HRU in outpatients with hyperkalemia. Research design and methods A retrospective noncomparative study using claims data from the HealthVerity warehouse, which included outpatients in the United States who initiated SZC between January and December 2019 (index date) with ≥6 months’ continuous coverage before (baseline) and after (follow-up) the index date (total coverage of 12 months). The study aimed to describe HRU with long-term and short-term SZC (defined as >90 and ≤90 days’ supply, respectively, during 180 days’ follow-up) and identify characteristics associated with long-term versus short-term therapy. Results Of 1153 patients, 748 (64.9%) received short-term and 405 (35.1%) received long-term therapy. During follow-up, lower proportions of patients on long-term versus short-term therapy had hyperkalemia-related hospitalizations (10.1% vs 15.1%; P < 0.05) and all-cause hospitalizations (22.5% vs 29.3%; P < 0.05). Hyperkalemia-related and all-cause hospitalization proportions were 33.0% and 23.3% lower, respectively. Predictors of long-term therapy included stage 3 chronic kidney disease. Conclusions Approximately one-third of patients with hyperkalemia received long-term SZC therapy. Hyperkalemia-related and all-cause hospitalization proportions were lower with long-term therapy, although further confirmatory studies are needed.

An evaluation of sodium zirconium cyclosilicate: a new treatment option for hyperkalaemia in China

ABSTRACT Introduction Hyperkalemia is a common complication of chronic kidney disease (CKD), diabetes mellitus (DM), and heart failure (HF) that can lead to severe arrhythmias and sudden death and is associated with a higher risk of mortality. Therefore, the prevention and treatment of hyperkalemia is important. Sodium zirconium cyclosilicate (SZC), a new oral potassium-lowering drug, has offered an additional treatment option for Chinese patients with hyperkalemia since its launch in China in late 2019, and some experience has been accumulated regarding its efficacy and safety. Areas covered In this review, the authors summarize the epidemiological features of hyperkalemia in China and review the clinical data regarding the use of sodium zirconium cyclosilicate in Chinese patients. Expert opinion The prevalence of hyperkalemia is particularly high in Chinese patients with chronic kidney disease and heart failure. In China, recent clinical studies have shown that SZC rapidly reduces serum potassium, maintains normal potassium concentration, and is well tolerated and safe. Two Chinese expert consensus statements have recommended the use of SZC for the acute correction and chronic maintenance of potassium concentration.

Sodium polystyrene sulfonate versus sodium zirconium cyclosilicate for the treatment of hyperkalemia in the emergency department

BackgroundHyperkalemia accounts for over 800,000 emergency department (ED) visits in the United States each year, and has been associated with significant morbidity and mortality likely due to fatal cardiac dysrhythmias. Previous studies have demonstrated reductions in mortality when potassium levels are normalized in the ED. Cation exchange resins, such as sodium polystyrene sulfonate (SPS) and sodium zirconium cyclosilicate (SZC), may be administered as a means of definitively eliminating potassium from the body. This practice is based on physician preference and is not supported by high quality data. Two studies evaluating the use of cation exchange resins versus standard treatment in the ED demonstrated reductions in serum potassium levels within two hours of administration; however, there have been no published studies investigating these agents in a head-to-head comparison. ObjectiveThe purpose of this study was to evaluate the efficacy and safety of SPS versus SZC in lowering serum potassium in patients presenting to the ED with hyperkalemia. MethodsThis was an institutional review board-approved, retrospective cohort study conducted at a single-site ED. All patients who received medications under the “ED Hyperkalemia Treatment” order set between August 26, 2019 and May 13, 2021 were eligible for inclusion. The primary outcome was the change in serum potassium from baseline to first repeat level following SPS or SZC administration in the ED. ResultsA total of 885 patients were screened with 54 patients in the SPS group and 51 patients in the SZC group included in the final analyses. The mean change in serum potassium from baseline to first repeat level following administration of the cation exchange resin was −1.1 mEq/L for both groups. ConclusionAdministration of SPS or SZC for the treatment of hyperkalemia in the ED resulted in similar reductions in serum potassium.

Impact of Sodium Zirconium Cyclosilicate Therapy on Nutrition Status in Patients with Hyperkalemia.

Background: Restriction of oral potassium intake is a necessary dietary intervention for managing chronic hyperkalemia. These dietary changes may have negative impacts on nutrition status, particularly in geriatric cohorts with multiple comorbidities. Sodium zirconium cyclosilicate (SZC) is a newly introduced potassium binder intended for patients with hyperkalemia. We aimed to investigate whether the improvements in hyperkalemia with SZC therapy and the liberation of potassium intake restriction may improve nutrition status in a primarily geriatric patient cohort with chronic hyperkalemia. Methods: Patients who were maintained on SZC therapy for at least 3 months were retrospectively studied. Following the initiation of SZC and improvement in hyperkalemia, instructions on the restriction of potassium intake were loosened according to the institutional protocol. The change in nutrition status during the 3 month therapeutic period using SZC was investigated by referencing the prognostic nutritional index score (PNI), geriatric nutritional risk index score (GNRI), and controlling nutritional status (CONUT) scores. Results: A total of 24 patients (median age 78 years, 58% men, median estimated glomerular filtration rate 29.8 mL/min//1.73 m2) were included. Serum potassium level decreased significantly from 5.4 (5.1, 5.9) to 4.4 (4.2, 4.9) mEq/L without any drug-related adverse events, including hypokalemia. Nutrition-related scores, including the PNI score, the GNRI score, and the CONUT score, improved significantly following 3 months of SZC therapy (p < 0.05 for all). Psoas muscle volume and average days for one movement also improved significantly during the therapeutic period (p < 0.05 for both). Conclusions: Mid-term SZC therapy and liberation of potassium intake restriction might improve nutrition status in geriatric patients with chronic hyperkalemia.

488 NOVEL POTASSIUM BINDERS IMPROVES RAASI THERAPY OPTIMIZATION IN HEART FAILURE: A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract Background Hyperkalemia (HK) often occurs among patients with heart failure (HF), particularly when treated with renin-angiotensin-aldosterone system inhibitors (RAASi). Even modest variations from normal potassium levels raise the risk of mortality and prompt patients to limit or cease disease-modifying treatment. Novel potassium binders (NPB), patiromer and sodium zirconium cyclosilicate, are approved for treatment of HK, but whether this results in a real optimization of HF treatment remains to be seen. Objectives To assess the efficacy of NPB on the persistence of therapy with RAASi in HF patients. Methods PubMed and Web of Science 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 main outcome was the proportion of HF patients achieving target dose of RAASi. Secondary outcomes were the reduction in potassium levels, hyperkalemia events and persistence of therapy with RAASi in the overall population. Results Eight studies, with a total of 2247 patients were included. NPB improved optimization of RAASi therapy in HF compared to placebo by 21% (95% CI: 5% – 39%), decreased potassium levels by 0.48 mEq/L (95% CI: 0.28–0.67) and decreased hyperkalemia events by 53% (95% CI: 34% – 64%) and improved the proportion of the overall study population on RAASi therapy by 28% (95% CI: 7% – 52%). Conclusion The present meta-analysis suggests that NPB are favorable in improving the proportion of patients on RAASi therapy, whether they have HF or not, in reducing potassium levels and hyperkalemia events.