Potassium binders (patiromer, sodium zirconium cyclosilicate)

AMT in HFrEFAMT in HFpEF

Removal by dialysis

What each drug's prescribing information says about removal by (haemo)dialysis. Where the label is silent, this page says so rather than inferring from protein binding.

PatiromerLabel does not address dialysis removal
Patiromer is not absorbed; the label contains no statement on dialysis.
Sodium zirconium cyclosilicateLabel does not address dialysis removal
Not absorbed; the label gives a haemodialysis dosing regimen (non-dialysis days) rather than a removal statement.
- “For patients on chronic hemodialysis, administer LOKELMA only on non-dialysis days.”
  LOKELMA (sodium zirconium cyclosilicate) PI, AstraZeneca (2025)· 2.2 Dosage Adjustment for Patients on Chronic Hemodialysis Source

Drugs and doses

Drug	Brands	Start	Target	Kidney dosing
Patiromer	Veltassa	8.4 g once daily	Titrate by 8.4 g at ≥1-week intervals to target K+; max 25.2 g once daily	No renal dose adjustment (93% of trial patients had CKD). No dialysis-specific labelling. Separate other oral drugs by 3 h (includes bisoprolol, carvedilol, nebivolol, mycophenolate). Monitor magnesium.
Sodium zirconium cyclosilicate (SZC)	Lokelma	10 g t.i.d. for up to 48 h (correction), then 10 g once daily; haemodialysis: 5 g once daily on non-dialysis days	Maintenance 5 g every other day to 15 g daily (HD: 5-15 g on non-dialysis days)	No CKD dose adjustment stated. Haemodialysis: dose only on non-dialysis days, guided by the pre-dialysis K after the long interdialytic interval. Each 5 g contains ~400 mg sodium (oedema warning, relevant in HF). Separate pH-dependent oral drugs by 2 h; lowers tacrolimus exposure.

Status by kidney stage

Stage	Initiate	Continue
G1	Allowed Can be used to treat confirmed hyperkalaemia (labelled for adults). Hyperkalaemia is uncommon at this stage. ESC 2026 HF makes no recommendation because clinical benefit is unproven.	Allowed Continue while needed to keep potassium in range and maintain RAASi/MRA.
G2	Allowed Same as G1. Use only for confirmed hyperkalaemia, mainly to maintain or uptitrate RAASi/MRA.	Allowed Continue as needed.
G3a	Allowed Allowed to manage hyperkalaemia and keep ACE-I/ARNI/ARB/MRA going. ESC CVD-CKD 2026 says binders 'may be useful' in HF+CKD, and KDIGO 2024 places them second line before reducing RASi/MRA (action threshold K >5.5).	Allowed Continue as needed; no renal dose adjustment.
G3b	Allowed Allowed. This is the population where binder-enabled RAASi optimisation was tested (DIAMOND and REALIZE-K enrolled eGFR ≥30; PRIORITIZE-HF eGFR 20-59). Outcome benefit is unproven.	Allowed Continue as needed; no renal dose adjustment.
G4	Allowed Allowed by label (no renal dose adjustment; 93% of patiromer trial patients had CKD). HF trials largely excluded eGFR <30, so HF-specific evidence is extrapolated.	Allowed Continue as needed.
G5	Allowed Allowed by label; no renal dose adjustment. Potassium binders are listed for refractory hyperkalaemia in CKD. Severe or refractory hyperkalaemia with very low GFR or low urine output may need emergent dialysis instead.	Allowed Continue as needed.
dialysis	Use with caution SZC has a labelled haemodialysis regimen: 5 g once daily on non-dialysis days only (10 g if K >6.5), titrated on the pre-dialysis K after the long interval; watch for hypokalaemia (DIALIZE: 41% vs 1% responders). Patiromer has no dialysis-specific label statement; a small RCT (PEARL-HD) showed less hyperkalaemia.	Use with caution Continue with dose adjustment to the pre-dialysis potassium; reduce or stop if K falls below target or on acute illness (hypokalaemia risk).
aki	Use with caution Binders work slowly and both labels say they must not be used as emergency treatment for life-threatening hyperkalaemia. In AKI, treat acute hyperkalaemia by standard emergency measures (dialysis if refractory or oliguric). A binder may be added for subacute control.	Use with caution May continue if already established; reassess dose as kidney function recovers to avoid hypokalaemia.
transplant	Use with caution No transplant outcome data, but there are labelled immunosuppressant interactions. SZC decreases tacrolimus exposure (gastric pH effect; give other drugs 2 h apart). Patiromer must be separated by 3 h from mycophenolate mofetil; tacrolimus showed no clinically important interaction.	Use with caution Continue with drug spacing and tacrolimus level monitoring.

Cutoffs recorded from the sources

potassium > 5.5 mmol/L → allowed (initiate; patiromer, sodium-zirconium-cyclosilicate)
“Figure 32 | Actions to manage hyperkalemia (potassium >5.5 mmol/l) in chronic kidney disease.” — kdigo2024-ckd, p. 113
potassium > 5.5 mmol/L → allowed (initiate; patiromer, sodium-zirconium-cyclosilicate)
“A conservative threshold for action is recurrent serum potassium values >5.5 mmol/L.” — esc2026-ckd, p. 19
potassium > 5.7 mmol/L → allowed (initiate; patiromer, sodium-zirconium-cyclosilicate)
“Higher thresholds for action (e.g. >5.7 mmol/L) are often justified in CKD due to chronic hyperkalaemia, aiming to avoid serum potassium levels of 6.0 mmol/L or above.” — esc2026-ckd, p. 19
potassium > 5 mmol/L → allowed (initiate; patiromer, sodium-zirconium-cyclosilicate)
“In patients with chronic or recurrent hyperkalaemia on RAAS inhibitors therapy an approved Kþ-lowering agent may be initiated as soon as Kþ levels are confirmed as >5.0 mEq/L.” — esc2021-supp, p. 35
potassium >= 5.5 mEq/L → allowed (initiate; patiromer, sodium-zirconium-cyclosilicate)
“In patients with HF who experience hyperkalemia (serum potassium level ‡5.5 mEq/L) while taking a renin-angiotensin-aldosterone system inhibitor (RAASi), the effectiveness of potassium binders (patiromer, sodium zirconium cyclosilicate) to improve outcomes by facilitating continuation of RAASi therapy is uncertain (5,6).” — aha2022, p. 48
potassium > 5.5 mmol/L → caution (dose_reduce; RAASi/MRA (context))
“Severe hyperkalaemia (potassium >5.5 or >6 mmol/L) should lead to temporary down-titration or discontinuation of MRAs and/or ARNIs/ACE-Is/ARBs (see Supplementary data online, Tables S4, S5 and S9).” — esc2026, p. 35
potassium > 5.5 mmol/L → caution (dose_reduce; MRA (context))
“If K+ rises above 5.5 mmol/L, halve a dose and monitor blood chemistry closely.” — esc2026-supp, p. 18
potassium > 6 mmol/L → not-recommended (hold; MRA (context))
“If K+ rises to >6.0 mmol/L, interrupt MRA immediately and seek specialist advice.” — esc2026-supp, p. 18
potassium >= 6 mmol/L → not-recommended (hold; ACEI/ARB/finerenone (context))
“Stop ACEI/ARB/finerenone if potassium ≥6.0 mmol/L; in 5.5–6.0 mmol/L range, should optimize other factors and consider dose reduction, where applicable (Section 3.7.1).” — esc2026-ckd, p. 33
potassium > 6 mEq/L → not-recommended (hold; RAASi (context))
“Generally, dose reduction of these agents is advised if potassium is between 5.5 mEq/L and 6 mEq/L and temporarily termination if potassium is above 6 mEq/L, with reinstitution of the drug only when the potassium drops below 5.5 mEq/L.” — mullens2022, p. 13
potassium < 5 mEq/L → allowed (initiate; RAASi (context))
“In patients with eGFR <60 ml/min per 1.73 m2, initiate ACEi, ARB, sMRA, or nsMRA if serum potassium is <5 mEq/l.” — kdigo2026-hf, p. 11
potassium > 6.5 mEq/L → caution (initiate; sodium-zirconium-cyclosilicate)
“The recommended starting dose is 5 g once daily on non-dialysis days. Consider a starting dose of 10 g once daily on non-dialysis days in patients with serum potassium greater than 6.5 mEq/L.” — fda-sodium-zirconium-cyclosilicate, Section 2.2 Dosage Adjustment for Patients on Chronic Hemodialysis
potassium < 3.5 mEq/L → caution (dose_reduce; sodium-zirconium-cyclosilicate, patiromer)
“In clinical trials in patients who were not on dialysis, 4.1% of LOKELMA-treated patients developed hypokalemia with a serum potassium value less than 3.5 mEq/L, which resolved with dosage reduction or discontinuation of LOKELMA.” — fda-sodium-zirconium-cyclosilicate, Section 6.1 Laboratory Abnormalities
other < 1.4 mg/dL serum magnesium → caution (continue; patiromer)
“Approximately 9% of adult patients in clinical trials developed hypomagnesemia with a serum magnesium value < 1.4 mg/dL.” — fda-patiromer, Section 6.1 Laboratory Abnormalities
other >= 3 hours separation from other oral drugs → caution (continue; patiromer)
“Administer Veltassa at least 3 hours before or 3 hours after other oral medications except those shown to not have a clinically important interaction [see Drug Interactions (7) and Clinical Pharmacology (12.3)].” — fda-patiromer, Section 2.1 General Information
other >= 2 hours separation from other oral drugs → caution (continue; sodium-zirconium-cyclosilicate)
“In general, other oral medications should be administered at least 2 hours before or 2 hours after LOKELMA [see Drug Interactions (7) ].” — fda-sodium-zirconium-cyclosilicate, Section 2.3 Reconstitution and Administration
egfr < 30 mL/min/1.73m2 → allowed (initiate; patiromer, sodium-zirconium-cyclosilicate)
“Patients were excluded if they had an estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m2, systolic blood pressure <90 mmHg or symptomatic hypotension, or any significant comorbidity that could change their clinical course independent of heart failure.” — butler2022, Methods (Patients)

Trial evidence (informational)

DIAMOND · HFrEF (LVEF ≤40%) with RAASi hyperkalaemia (two K >5.0) or prior RAASi reduction; eGFR ≥30
Adjusted mean change in K (primary): +0.03 vs +0.13 mmol/L; difference −0.10 mmol/L, P<0.001
“At the end of treatment, the median (interquartile range) duration of follow-up was 27 (13–43) weeks, the adjusted mean change in potassium was +0.03 mmol/l in the patiromer group and +0.13 mmol/l in the placebo group [difference in the adjusted mean change between patiromer and placebo: −0.10 mmol/l (95% confidence interval, CI −0.13, 0.07); P < 0.001].” — butler2022, Abstract (Methods and results)
DIAMOND · as above
Hyperkalaemia >5.5 / MRA dose reduction: HR 0.63 (0.45-0.87) / HR 0.62 (0.45-0.87)
“Risk of hyperkalemia >5.5 mmol/l [hazard ratio (HR) 0.63; 95% CI 0.45, 0.87; P = 0.006), reduction of MRA dose (HR 0.62; 95% CI 0.45, 0.87; P = 0.006), and total adjusted hyperkalemia events/100 person-years (77.7 vs. 118.2; HR 0.66; 95% CI 0.53, 0.81; P < 0.001) were lower with patiromer.” — butler2022, Abstract (Methods and results)
REALIZE-K · HFrEF (LVEF ≤40%), MRA-induced hyperkalaemia, eGFR ≥30 (randomized withdrawal, n=203)
Optimal response (normokalaemia on spironolactone ≥25 mg): 71% vs 36%; OR 4.45 (2.89-6.86)
“Higher percentage of SZC- vs placebo-treated participants had optimal response (71% vs 36%; OR: 4.45; 95% CI: 2.89-6.86; P < 0.001).” — kosiborod2025, Abstract (Results)
REALIZE-K · as above
CV death or worsening HF (exploratory): 11 (11%) SZC vs 3 (3%) placebo; nominal P=0.034
“Composite of cardiovascular (CV) death or worsening HF occurred in 11 (11%) participants in the SZC group (1 with CV death, 10 with HF events) and 3 (3%) participants in the placebo group (1 with CV death, 2 with HF events; log-rank nominal P = 0.034).” — kosiborod2025, Abstract (Results)
PRIORITIZE-HF · Symptomatic HFrEF at hyperkalaemia risk (eGFR 20-59), n=182, terminated early (COVID-19)
RAASi intensity categories at 12 weeks: No significant difference (P=0.43)
“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).” — tardif2023, Abstract (Methods and results)
DIALIZE · 196 HD patients with predialysis hyperkalaemia
Responders (predialysis K 4.0-5.0 in ≥3/4 sessions): 41.2% vs 1.0%, P<0.001
“Of 97 patients receiving sodium zirconium cyclosilicate, 41.2% met the primary end point and were deemed treatment responders compared with 1.0% of 99 patients receiving placebo (P<0.001).” — fishbane2019, Abstract (Results)
DIALIZE-Outcomes · 2690 HD patients with predialysis K ≥5.5
SCD, stroke, arrhythmia-related events: 8.8% vs 8.9%; HR 0.98 (0.76-1.26)
“No treatment effect was observed on the primary composite end point (SZC, 8.8% [119 patients] vs. placebo, 8.9% [119 patients]; hazard ratio 0.98; 95% confidence interval 0.76-1.26) or individual cardiovascular outcomes.” — fishbane2025, Abstract (Results)
PEARL-HD · ESKD on thrice-weekly HD (n=31 analysed)
Episodes of K ≥5.5: Fewer hyperkalaemia episodes with patiromer
“Patiromer administered daily reduced the frequency of hyperkalemia in study participants with ESKD who receive thrice-weekly HD. Larger studies are needed to determine whether patiromer reduces significant cardiac events.” — middleton2024, Abstract (Conclusion)

Acute kidney injury

No AKI-specific binder evidence. Both labels state the drugs are not for emergency treatment of life-threatening hyperkalaemia (delayed onset). ESC CVD-CKD warns that severe or refractory hyperkalaemia with severely decreased GFR or low urine output may need emergent dialysis.

“Limitation of Use: Veltassa should not be used as an emergency treatment for life-threatening hyperkalemia because of its delayed onset of action [see Clinical Pharmacology (12.2)].”
VELTASSA (patiromer) PI, Vifor (2025)· Section 1 Indications and Usage Source
“LOKELMA should not be used as an emergency treatment for life-threatening hyperkalemia because of its delayed onset of action [see Clinical Pharmacology (12.2) and Clinical Studies (14)].”
LOKELMA (sodium zirconium cyclosilicate) PI, AstraZeneca (2025)· Section 1 Indications and Usage Source
“Importantly, insulin-dextrose infusions do not result in any potassium excretion, so severe and refractory hyperkalaemia in patients with severely decreased GFR or low urine output may need emergent dialysis.”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 19 Source
“Severe hyperkalaemia can result in life-threatening arrhythmias, particularly when serum potassium is >6.5 mmol/L.”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 19 Source

Dialysis

SZC is the only binder with labelled haemodialysis dosing (non-dialysis days, 5-15 g; DIALIZE 41% vs 1% responders; no difference in interdialytic weight gain). DIALIZE-Outcomes (n=2690, stopped early) improved normokalaemia but not arrhythmia-related outcomes (HR 0.98). Patiromer: no labelled dialysis regimen; PEARL-HD (small RCT) reduced hyperkalaemia episodes. ESC CVD-CKD lists potassium binders among dialysis strategies.

Trials: DIALIZE, DIALIZE-Outcomes

“For patients on chronic hemodialysis, administer LOKELMA only on non-dialysis days.”
LOKELMA (sodium zirconium cyclosilicate) PI, AstraZeneca (2025)· Section 2.2 Dosage Adjustment for Patients on Chronic Hemodialysis Source
“The recommended starting dose is 5 g once daily on non-dialysis days. Consider a starting dose of 10 g once daily on non-dialysis days in patients with serum potassium greater than 6.5 mEq/L.”
LOKELMA (sodium zirconium cyclosilicate) PI, AstraZeneca (2025)· Section 2.2 Dosage Adjustment for Patients on Chronic Hemodialysis Source
“A greater proportion of patients were responders in the LOKELMA arm as compared to placebo (41% vs 1%, respectively; p<0.001).”
LOKELMA (sodium zirconium cyclosilicate) PI, AstraZeneca (2025)· Section 14.5 Study 4 Source
“In a clinical trial of LOKELMA in patients on chronic hemodialysis in which most patients were treated with doses of 5 to 10 g once daily on non-dialysis days, there was no difference in the mean change from baseline in interdialytic weight gain (a measure of fluid retention) between the LOKELMA and placebo groups.”
LOKELMA (sodium zirconium cyclosilicate) PI, AstraZeneca (2025)· Section 5.2 Edema Source
“In a clinical trial of LOKELMA in patients on chronic hemodialysis, 5% of patients developed pre-dialysis hypokalemia (serum potassium <3.5 mEq/L) in both the LOKELMA and placebo groups; 3% and 1% of patients developed a serum potassium < 3.0 mEq/L in the LOKELMA and placebo groups, respectively.”
LOKELMA (sodium zirconium cyclosilicate) PI, AstraZeneca (2025)· Section 6.1 Laboratory Abnormalities Source
“Of 97 patients receiving sodium zirconium cyclosilicate, 41.2% met the primary end point and were deemed treatment responders compared with 1.0% of 99 patients receiving placebo (P<0.001).”
Fishbane S et al. DIALIZE: sodium zirconium cyclosilicate in hemodialysis. J Am Soc Nephrol 2019 (PMC6727265) (2019)· Abstract (Results) Source
“No treatment effect was observed on the primary composite end point (SZC, 8.8% [119 patients] vs. placebo, 8.9% [119 patients]; hazard ratio 0.98; 95% confidence interval 0.76-1.26) or individual cardiovascular outcomes.”
Fishbane S et al. DIALIZE-Outcomes. Kidney Int 2025 (PMID 40618849, abstract) (2025)· Abstract (Results) Source
“Maintenance of normokalemia at 12 months was significantly better with SZC than placebo (74.0% [495 patients] vs. 47.0% [293 patients]; odds ratio 3.36; 95% confidence interval 2.64-4.26).”
Fishbane S et al. DIALIZE-Outcomes. Kidney Int 2025 (PMID 40618849, abstract) (2025)· Abstract (Results) Source
“Patiromer administered daily reduced the frequency of hyperkalemia in study participants with ESKD who receive thrice-weekly HD. Larger studies are needed to determine whether patiromer reduces significant cardiac events.”
Middleton JP et al. Randomized trial of patiromer on efficacy to reduce episodic hyperkalemia in patients with ESKD treated with hemodialysis (PEARL-HD). Kidney Int Rep 2024 (PMC11551111, full text) (2024)· Abstract (Conclusion) Source
“Minimize electrolyte shifts and avoid sudden cardiac death • Dietary potassium restriction • Potassium binders • Titrate dialysate prescription”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 68 Source
“The effect of oral potassium binders on clinical outcomes in HF has not been established.”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 39, Section 6.2.3.2 Source

Kidney transplant

No transplant outcome data. Interactions with immunosuppressants: SZC lowers tacrolimus exposure; patiromer needs 3-h separation from mycophenolate mofetil (tacrolimus showed no clinically important interaction).

“In another drug-drug interaction study in healthy volunteers, co-administration of LOKELMA 15 g decreased the systemic exposures of tacrolimus (Figure 2), likely due to LOKELMA’s action on elevating gastric pH.”
LOKELMA (sodium zirconium cyclosilicate) PI, AstraZeneca (2025)· Section 12.3 Pharmacokinetics (Drug Interactions) Source
“Immunosuppressants Mycophenolate mofetil”
VELTASSA (patiromer) PI, Vifor (2025)· Section 7.1, Table 2 Source
“Immunosuppressants Tacrolimus”
VELTASSA (patiromer) PI, Vifor (2025)· Section 7.2, Table 3 Source
“The utilization of oral potassium binders can minimize the additional risk of hyperkalemia from using RASi and MRA and facilitate more permanent use of GDMT.”
Ghimire A et al. Heart Failure in Kidney Transplant Recipients: Narrative Review of Risk Factors, Therapy, and Current Gaps. Cardiol Ther 2026 (PMC12988941) (2026)· Strategies to enhance GDMT uptake Source

Albuminuria

No albuminuria-specific binder statement. KDIGO 2024 frames binders as a way to keep RASi in CKD (where RASi is indicated for A2-A3).

“Practice Point 3.6.3: Hyperkalemia associated with use of RASi can often be managed by measures to reduce the serum potassium levels rather than decreasing the dose or stopping RASi.”
KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of CKD (2024)· p. 44 Source
“Use of these newer exchange agents may help facilitate essential use of RASi/MRA.”
KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of CKD (2024)· p. 111 Source

Monitoring

Titrate at ≥1-week intervals on serum potassium. In haemodialysis, check pre-dialysis K one week after each SZC change. Patiromer: monitor magnesium. SZC: monitor for oedema in HF/CKD (sodium ~400 mg per 5 g) and adjust diuretics. When restarting or uptitrating RAASi, check K/creatinine within 2-4 weeks (KDIGO).

“Adults: The recommended starting dose of Veltassa is 8.4 grams patiromer orally once daily. The dose can be up-titrated based on serum potassium level at 1-week or longer intervals, in increments of 8.4 grams.”
VELTASSA (patiromer) PI, Vifor (2025)· Section 2.2 Recommended Dosing and Titration Source
“During initiation and after a dose adjustment, assess serum potassium after one week. The recommended maintenance dose range is from 5 g to 15 g once daily, on non-dialysis days.”
LOKELMA (sodium zirconium cyclosilicate) PI, AstraZeneca (2025)· Section 2.2 Dosage Adjustment for Patients on Chronic Hemodialysis Source
“Monitor serum magnesium. Consider magnesium supplementation in patients who develop low serum magnesium levels on Veltassa.”
VELTASSA (patiromer) PI, Vifor (2025)· Section 5.2 Hypomagnesemia Source
“Monitor for signs of edema, particularly in patients who should restrict their sodium intake or are prone to fluid overload (e.g., heart failure or renal disease). Advise patients to adjust dietary sodium, if appropriate.”
LOKELMA (sodium zirconium cyclosilicate) PI, AstraZeneca (2025)· Section 5.2 Edema Source
“Practice Point 3.6.2: Changes in BP, serum creatinine, and serum potassium should be checked within 2–4 weeks of initiation or increase in the dose of a RASi, depending on the current GFR and serum potassium.”
KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of CKD (2024)· p. 44 Source

In-hospital initiation

Not for emergency treatment of life-threatening hyperkalaemia (onset is delayed). SZC 10 g t.i.d. for up to 48 h can be used for initial correction. Insulin-dextrose shifts but does not remove potassium.

“LOKELMA should not be used as an emergency treatment for life-threatening hyperkalemia because of its delayed onset of action [see Clinical Pharmacology (12.2) and Clinical Studies (14)].”
LOKELMA (sodium zirconium cyclosilicate) PI, AstraZeneca (2025)· Section 1 Indications and Usage Source
“For initial treatment of hyperkalemia, the recommended dose of LOKELMA is 10 g administered three times a day for up to 48 hours.”
LOKELMA (sodium zirconium cyclosilicate) PI, AstraZeneca (2025)· Section 2.1 Recommended Dosage Source
“Importantly, insulin-dextrose infusions do not result in any potassium excretion, so severe and refractory hyperkalaemia in patients with severely decreased GFR or low urine output may need emergent dialysis.”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 19 Source

Outpatient

Main use is chronic outpatient RAASi/MRA enablement (DIAMOND, REALIZE-K run-in). ESC 2026 makes no recommendation; ACC 2024 says 'consider'; KDIGO 2024 puts binders before reducing RASi/MRA.

“No specific recommendations for the use of potassium binders are included in the guideline at current time, due to insufficient evidence for clinical benefit.”
2026 ESC Guidelines for the diagnosis and treatment of heart failure (2026)· p. 33 Source
“Consider treating with patiromer or sodium zirconium cyclosilicate”
2024 ACC Expert Consensus Decision Pathway for Treatment of HFrEF (2024)· p. 31 Source
“2nd line: Medications Consider: • Appropriate use of diuretics • Optimize serum bicarbonate levels • Licensed potassium exchange agents 3rd line: Last resort • Reduce dose or discontinue RASi/MRA”
KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of CKD (2024)· p. 113 Source
“Patiromer allowed for 85% of participants to be optimized on GDMT.”
2024 ACC Expert Consensus Decision Pathway for Treatment of HFrEF (2024)· p. 18 Source

Where sources disagree

Should binders be used to enable RAASi/MRA in HF (recommendation strength)?

“No specific recommendations for the use of potassium binders are included in the guideline at current time, due to insufficient evidence for clinical benefit.”
2026 ESC Guidelines for the diagnosis and treatment of heart failure (2026)· p. 33 Source
“In patients with HF who experience hyperkalemia (serum potassium level ‡5.5 mEq/L) while taking a renin-angiotensin-aldosterone system inhibitor (RAASi), the effectiveness of potassium binders (patiromer, sodium zirconium cyclosilicate) to improve outcomes by facilitating continuation of RAASi therapy is uncertain (5,6).”
2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure (2022)· p. 48 Source
“Treatment with oral potassium binders (patiromer or sodium zirconium cyclosilicate) may be useful in patients with HF and CKD to decrease serum potassium, reduce the risk of hyperkalaemia, and avoid down-titration or withdrawal of risk-modifying therapies such as ACEI/ARBs, ARNIs, and MRAs.”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 39 Source
“2nd line: Medications Consider: • Appropriate use of diuretics • Optimize serum bicarbonate levels • Licensed potassium exchange agents 3rd line: Last resort • Reduce dose or discontinue RASi/MRA”
KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of CKD (2024)· p. 113 Source
“Consider treating with patiromer or sodium zirconium cyclosilicate”
2024 ACC Expert Consensus Decision Pathway for Treatment of HFrEF (2024)· p. 31 Source
“In patients with chronic or recurrent hyperkalaemia on RAAS inhibitors therapy an approved Kþ-lowering agent may be initiated as soon as Kþ levels are confirmed as >5.0 mEq/L.”
2021 ESC HF Guidelines Supplementary Data (2021)· p. 35 Source

Tool uses esc2026: ESC 2026 HF is primary and gives no recommendation (insufficient evidence of clinical benefit). FDA labels permit use for hyperkalaemia, so cells are 'allowed' (never 'recommended'). The KDIGO/ESC CVD-CKD sequence (binder before cutting RASi/MRA) is shown as supporting text.

Potassium threshold at which to start a binder / act on RAASi

“In patients with chronic or recurrent hyperkalaemia on RAAS inhibitors therapy an approved Kþ-lowering agent may be initiated as soon as Kþ levels are confirmed as >5.0 mEq/L.”
2021 ESC HF Guidelines Supplementary Data (2021)· p. 35 Source
“The protocol required patients to have hyperkalemia at screening (defined as two serum potassium values of >5.0 mmol/l) while receiving an angiotensin-converting enzyme inhibitor (ACEi), angiotensin receptor blocker (ARB), angiotensin receptor-neprilysin inhibitor (ARNi), and/or MRA therapy.”
Butler J, Anker SD, Lund LH, et al. Patiromer for the management of hyperkalemia in HFrEF: the DIAMOND trial. Eur Heart J 2022;43:4362-73 (PMC9622299, full text) (2022)· Methods (Patients) Source
“Figure 32 | Actions to manage hyperkalemia (potassium >5.5 mmol/l) in chronic kidney disease.”
KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of CKD (2024)· p. 113 Source
“A conservative threshold for action is recurrent serum potassium values >5.5 mmol/L.”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 19 Source
“Higher thresholds for action (e.g. >5.7 mmol/L) are often justified in CKD due to chronic hyperkalaemia, aiming to avoid serum potassium levels of 6.0 mmol/L or above.”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 19 Source
“Severe hyperkalaemia (potassium >5.5 or >6 mmol/L) should lead to temporary down-titration or discontinuation of MRAs and/or ARNIs/ACE-Is/ARBs (see Supplementary data online, Tables S4, S5 and S9).”
2026 ESC Guidelines for the diagnosis and treatment of heart failure (2026)· p. 35 Source
“Stop ACEI/ARB/finerenone if potassium ≥6.0 mmol/L; in 5.5–6.0 mmol/L range, should optimize other factors and consider dose reduction, where applicable (Section 3.7.1).”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 33 Source
“Generally, dose reduction of these agents is advised if potassium is between 5.5 mEq/L and 6 mEq/L and temporarily termination if potassium is above 6 mEq/L, with reinstitution of the drug only when the potassium drops below 5.5 mEq/L.”
Mullens 2022 EJHF: Renal effects of GDMT in HF, HFA/ESC consensus statement (2022)· p. 13 Source

Tool uses kdigo2024-ckd: No FDA label sets a start threshold. Default proposed: consider a binder for confirmed K >5.5 (KDIGO 2024 Figure 32; ESC CVD-CKD conservative threshold), reduce RAASi/MRA at >5.5 if mitigation fails, stop at ≥6.0 (ESC CVD-CKD, ESC 2026 supp). Make it user-adjustable (5.0 per DIAMOND/ESC 2021; 5.7 per ESC CVD-CKD for chronic CKD).

SZC sodium load, oedema and HF events

“In the REALIZE-K trial, there was a signal towards more HF deterioration with sodium zirconium cyclosilicate as compared with placebo, although the trial was not powered to detect clinical outcomes.”
2026 ESC Guidelines for the diagnosis and treatment of heart failure (2026)· p. 33 Source
“Although underpowered for clinical outcomes, more participants had HF events with SZC than placebo, which should be factored into the clinical decision making.”
Kosiborod MN et al. Sodium zirconium cyclosilicate for management of hyperkalemia during spironolactone optimization in patients with heart failure (REALIZE-K). J Am Coll Cardiol 2025;85:971-984 (PubMed abstract, PMID 39566872) (2025)· Abstract (Conclusions) Source
“Monitor for signs of edema, particularly in patients who should restrict their sodium intake or are prone to fluid overload (e.g., heart failure or renal disease). Advise patients to adjust dietary sodium, if appropriate.”
LOKELMA (sodium zirconium cyclosilicate) PI, AstraZeneca (2025)· Section 5.2 Edema Source
“Risks of HHF (any/primary) (adjusted hazard ratios [HRs], 1.373; 95% confidence interval [CI], 1.337 to 1.410), major edema encounter (HR, 1.330; 95% CI, 1.298 to 1.363), and death (HR, 1.287; 95% CI, 1.255 to 1.320) were also significantly higher in the SZC cohort compared with the PAT cohort (P < 0.05).”
Desai NR et al. The association of heart failure and edema events between patients initiating SZC or patiromer. Kidney360 2024;5:1835-1843 (PMC11687973, full text; CSL Vifor-funded claims analysis) (2024)· Abstract (Results) Source
“In a clinical trial of LOKELMA in patients on chronic hemodialysis in which most patients were treated with doses of 5 to 10 g once daily on non-dialysis days, there was no difference in the mean change from baseline in interdialytic weight gain (a measure of fluid retention) between the LOKELMA and placebo groups.”
LOKELMA (sodium zirconium cyclosilicate) PI, AstraZeneca (2025)· Section 5.2 Edema Source
“At the end of the open‐label phase, 11.6% of patients remained hyperkalaemic (sK+ >5.0 mEq/L) despite SZC titration; 1.1% had experienced an oedema‐related adverse event.”
Petrie MC et al. SZC, hyperkalaemia, and spironolactone optimization in HFrEF: the REALIZE-K open-label run-in phase. Eur J Heart Fail 2025 (PMC12482837, full text) (2025)· Results (Cohort 1) Source

Tool uses fda-sodium-zirconium-cyclosilicate: Label: monitor for oedema in HF/renal disease and adjust diuretics. REALIZE-K showed a signal of more HF events (underpowered), and a sponsor-competitor-funded claims study found more HF hospitalisations vs patiromer. In HD, DIALIZE showed no interdialytic weight-gain difference. Show a caution note for SZC in congested HF. No preference between drugs is proposed (owner decision).

Dialysis use: SZC labelled vs patiromer not labelled

“For patients on chronic hemodialysis, administer LOKELMA only on non-dialysis days.”
LOKELMA (sodium zirconium cyclosilicate) PI, AstraZeneca (2025)· Section 2.2 Dosage Adjustment for Patients on Chronic Hemodialysis Source
“No special dosing adjustments are needed for patients with renal impairment.”
VELTASSA (patiromer) PI, Vifor (2025)· Section 8.6 Renal Impairment Source
“Patiromer administered daily reduced the frequency of hyperkalemia in study participants with ESKD who receive thrice-weekly HD. Larger studies are needed to determine whether patiromer reduces significant cardiac events.”
Middleton JP et al. Randomized trial of patiromer on efficacy to reduce episodic hyperkalemia in patients with ESKD treated with hemodialysis (PEARL-HD). Kidney Int Rep 2024 (PMC11551111, full text) (2024)· Abstract (Conclusion) Source
“No treatment effect was observed on the primary composite end point (SZC, 8.8% [119 patients] vs. placebo, 8.9% [119 patients]; hazard ratio 0.98; 95% confidence interval 0.76-1.26) or individual cardiovascular outcomes.”
Fishbane S et al. DIALIZE-Outcomes. Kidney Int 2025 (PMID 40618849, abstract) (2025)· Abstract (Results) Source

Tool uses fda-sodium-zirconium-cyclosilicate: SZC has an explicit HD regimen (label). Patiromer has no dialysis-specific label text and only small RCT data. Dialysis cell = 'caution' for the class, with drug-specific notes.

HF trial evidence below eGFR 30 vs label permission

“Patients were excluded if they had an estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m2, systolic blood pressure <90 mmHg or symptomatic hypotension, or any significant comorbidity that could change their clinical course independent of heart failure.”
Butler J, Anker SD, Lund LH, et al. Patiromer for the management of hyperkalemia in HFrEF: the DIAMOND trial. Eur Heart J 2022;43:4362-73 (PMC9622299, full text) (2022)· Methods (Patients) Source
“prevalent hyperkalaemia (Cohort 1), defined as sK+ 5.1–5.9 mEq/L at screening and estimated glomerular filtration rate (eGFR) ≥30 ml/min/1.73 m2”
Petrie MC et al. SZC, hyperkalaemia, and spironolactone optimization in HFrEF: the REALIZE-K open-label run-in phase. Eur J Heart Fail 2025 (PMC12482837, full text) (2025)· Methods Source
“estimated glomerular filtration rate (eGFR) 20 to 44 mL/min/1.73 m2 [calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) equation] and serum potassium concentration between 4.0 and 5.5 mmol/L”
Tardif JC et al. Potassium reduction with sodium zirconium cyclosilicate in patients with heart failure (PRIORITIZE-HF). ESC Heart Fail 2023;10:1066-1076 (PMC10053160, full text) (2023)· Methods (Study population) Source
“Of the 666 adult patients treated with Veltassa in clinical studies, 93% had chronic kidney disease (CKD).”
VELTASSA (patiromer) PI, Vifor (2025)· Section 8.6 Renal Impairment Source
“However, due to the trial exclusion criteria, only 43 patients had an eGFR <30 ml/min/1.73 m2 [82].”
Bergen K, Spaak J. What to do with key cardiovascular drugs when kidney function worsens? Clin Kidney J 2026;19:sfaf354 (PMC12793518, full text) (2026)· Potassium binders section Source

Tool uses fda-patiromer: Labels impose no eGFR restriction (patiromer trials were 93% CKD). HF-specific RAASi-enablement trials mostly required eGFR ≥30, so G4/G5 = 'allowed' (extrapolated), not 'recommended'.

Open questions

Should the tool suggest a binder automatically when K exceeds the RAASi hold threshold, given ESC 2026 HF makes no recommendation? Proposed: show as an optional 'consider' with the REALIZE-K HF-event caveat for SZC.
Default K threshold for 'consider binder' (5.0 vs 5.5 vs 5.7) needs an owner decision; all are sourced.
Beta-blocker spacing: the patiromer label requires 3-h separation from bisoprolol, carvedilol and nebivolol (the HF beta-blockers). Should this appear as an interaction note in the beta-blocker profile?
Sodium polystyrene sulfonate is mentioned by ESC CVD-CKD (cost alternative, no randomized data) and is outside this class file. Include it?
No EMA SmPC was fetched (FDA labels exist for both). The EU Lokelma SmPC also has a dialysis regimen; fetch it if EU-specific wording is wanted.

Potassium binders (patiromer, sodium zirconium cyclosilicate)

AMT in HFrEFAMT in HFpEF

Open in the matrix

Removal by dialysis

What each drug's prescribing information says about removal by (haemo)dialysis. Where the label is silent, this page says so rather than inferring from protein binding.

PatiromerLabel does not address dialysis removal
Patiromer is not absorbed; the label contains no statement on dialysis.
Sodium zirconium cyclosilicateLabel does not address dialysis removal
Not absorbed; the label gives a haemodialysis dosing regimen (non-dialysis days) rather than a removal statement.
- “For patients on chronic hemodialysis, administer LOKELMA only on non-dialysis days.”
  LOKELMA (sodium zirconium cyclosilicate) PI, AstraZeneca (2025)· 2.2 Dosage Adjustment for Patients on Chronic Hemodialysis Source

Drugs and doses

Drug	Brands	Start	Target	Kidney dosing
Patiromer	Veltassa	8.4 g once daily	Titrate by 8.4 g at ≥1-week intervals to target K+; max 25.2 g once daily	No renal dose adjustment (93% of trial patients had CKD). No dialysis-specific labelling. Separate other oral drugs by 3 h (includes bisoprolol, carvedilol, nebivolol, mycophenolate). Monitor magnesium.
Sodium zirconium cyclosilicate (SZC)	Lokelma	10 g t.i.d. for up to 48 h (correction), then 10 g once daily; haemodialysis: 5 g once daily on non-dialysis days	Maintenance 5 g every other day to 15 g daily (HD: 5-15 g on non-dialysis days)	No CKD dose adjustment stated. Haemodialysis: dose only on non-dialysis days, guided by the pre-dialysis K after the long interdialytic interval. Each 5 g contains ~400 mg sodium (oedema warning, relevant in HF). Separate pH-dependent oral drugs by 2 h; lowers tacrolimus exposure.

Status by kidney stage

Stage	Initiate	Continue
G1	Allowed Can be used to treat confirmed hyperkalaemia (labelled for adults). Hyperkalaemia is uncommon at this stage. ESC 2026 HF makes no recommendation because clinical benefit is unproven.	Allowed Continue while needed to keep potassium in range and maintain RAASi/MRA.
G2	Allowed Same as G1. Use only for confirmed hyperkalaemia, mainly to maintain or uptitrate RAASi/MRA.	Allowed Continue as needed.
G3a	Allowed Allowed to manage hyperkalaemia and keep ACE-I/ARNI/ARB/MRA going. ESC CVD-CKD 2026 says binders 'may be useful' in HF+CKD, and KDIGO 2024 places them second line before reducing RASi/MRA (action threshold K >5.5).	Allowed Continue as needed; no renal dose adjustment.
G3b	Allowed Allowed. This is the population where binder-enabled RAASi optimisation was tested (DIAMOND and REALIZE-K enrolled eGFR ≥30; PRIORITIZE-HF eGFR 20-59). Outcome benefit is unproven.	Allowed Continue as needed; no renal dose adjustment.
G4	Allowed Allowed by label (no renal dose adjustment; 93% of patiromer trial patients had CKD). HF trials largely excluded eGFR <30, so HF-specific evidence is extrapolated.	Allowed Continue as needed.
G5	Allowed Allowed by label; no renal dose adjustment. Potassium binders are listed for refractory hyperkalaemia in CKD. Severe or refractory hyperkalaemia with very low GFR or low urine output may need emergent dialysis instead.	Allowed Continue as needed.
dialysis	Use with caution SZC has a labelled haemodialysis regimen: 5 g once daily on non-dialysis days only (10 g if K >6.5), titrated on the pre-dialysis K after the long interval; watch for hypokalaemia (DIALIZE: 41% vs 1% responders). Patiromer has no dialysis-specific label statement; a small RCT (PEARL-HD) showed less hyperkalaemia.	Use with caution Continue with dose adjustment to the pre-dialysis potassium; reduce or stop if K falls below target or on acute illness (hypokalaemia risk).
aki	Use with caution Binders work slowly and both labels say they must not be used as emergency treatment for life-threatening hyperkalaemia. In AKI, treat acute hyperkalaemia by standard emergency measures (dialysis if refractory or oliguric). A binder may be added for subacute control.	Use with caution May continue if already established; reassess dose as kidney function recovers to avoid hypokalaemia.
transplant	Use with caution No transplant outcome data, but there are labelled immunosuppressant interactions. SZC decreases tacrolimus exposure (gastric pH effect; give other drugs 2 h apart). Patiromer must be separated by 3 h from mycophenolate mofetil; tacrolimus showed no clinically important interaction.	Use with caution Continue with drug spacing and tacrolimus level monitoring.

Cutoffs recorded from the sources

potassium > 5.5 mmol/L → allowed (initiate; patiromer, sodium-zirconium-cyclosilicate)
“Figure 32 | Actions to manage hyperkalemia (potassium >5.5 mmol/l) in chronic kidney disease.” — kdigo2024-ckd, p. 113
potassium > 5.5 mmol/L → allowed (initiate; patiromer, sodium-zirconium-cyclosilicate)
“A conservative threshold for action is recurrent serum potassium values >5.5 mmol/L.” — esc2026-ckd, p. 19
potassium > 5.7 mmol/L → allowed (initiate; patiromer, sodium-zirconium-cyclosilicate)
“Higher thresholds for action (e.g. >5.7 mmol/L) are often justified in CKD due to chronic hyperkalaemia, aiming to avoid serum potassium levels of 6.0 mmol/L or above.” — esc2026-ckd, p. 19
potassium > 5 mmol/L → allowed (initiate; patiromer, sodium-zirconium-cyclosilicate)
“In patients with chronic or recurrent hyperkalaemia on RAAS inhibitors therapy an approved Kþ-lowering agent may be initiated as soon as Kþ levels are confirmed as >5.0 mEq/L.” — esc2021-supp, p. 35
potassium >= 5.5 mEq/L → allowed (initiate; patiromer, sodium-zirconium-cyclosilicate)
“In patients with HF who experience hyperkalemia (serum potassium level ‡5.5 mEq/L) while taking a renin-angiotensin-aldosterone system inhibitor (RAASi), the effectiveness of potassium binders (patiromer, sodium zirconium cyclosilicate) to improve outcomes by facilitating continuation of RAASi therapy is uncertain (5,6).” — aha2022, p. 48
potassium > 5.5 mmol/L → caution (dose_reduce; RAASi/MRA (context))
“Severe hyperkalaemia (potassium >5.5 or >6 mmol/L) should lead to temporary down-titration or discontinuation of MRAs and/or ARNIs/ACE-Is/ARBs (see Supplementary data online, Tables S4, S5 and S9).” — esc2026, p. 35
potassium > 5.5 mmol/L → caution (dose_reduce; MRA (context))
“If K+ rises above 5.5 mmol/L, halve a dose and monitor blood chemistry closely.” — esc2026-supp, p. 18
potassium > 6 mmol/L → not-recommended (hold; MRA (context))
“If K+ rises to >6.0 mmol/L, interrupt MRA immediately and seek specialist advice.” — esc2026-supp, p. 18
potassium >= 6 mmol/L → not-recommended (hold; ACEI/ARB/finerenone (context))
“Stop ACEI/ARB/finerenone if potassium ≥6.0 mmol/L; in 5.5–6.0 mmol/L range, should optimize other factors and consider dose reduction, where applicable (Section 3.7.1).” — esc2026-ckd, p. 33
potassium > 6 mEq/L → not-recommended (hold; RAASi (context))
“Generally, dose reduction of these agents is advised if potassium is between 5.5 mEq/L and 6 mEq/L and temporarily termination if potassium is above 6 mEq/L, with reinstitution of the drug only when the potassium drops below 5.5 mEq/L.” — mullens2022, p. 13
potassium < 5 mEq/L → allowed (initiate; RAASi (context))
“In patients with eGFR <60 ml/min per 1.73 m2, initiate ACEi, ARB, sMRA, or nsMRA if serum potassium is <5 mEq/l.” — kdigo2026-hf, p. 11
potassium > 6.5 mEq/L → caution (initiate; sodium-zirconium-cyclosilicate)
“The recommended starting dose is 5 g once daily on non-dialysis days. Consider a starting dose of 10 g once daily on non-dialysis days in patients with serum potassium greater than 6.5 mEq/L.” — fda-sodium-zirconium-cyclosilicate, Section 2.2 Dosage Adjustment for Patients on Chronic Hemodialysis
potassium < 3.5 mEq/L → caution (dose_reduce; sodium-zirconium-cyclosilicate, patiromer)
“In clinical trials in patients who were not on dialysis, 4.1% of LOKELMA-treated patients developed hypokalemia with a serum potassium value less than 3.5 mEq/L, which resolved with dosage reduction or discontinuation of LOKELMA.” — fda-sodium-zirconium-cyclosilicate, Section 6.1 Laboratory Abnormalities
other < 1.4 mg/dL serum magnesium → caution (continue; patiromer)
“Approximately 9% of adult patients in clinical trials developed hypomagnesemia with a serum magnesium value < 1.4 mg/dL.” — fda-patiromer, Section 6.1 Laboratory Abnormalities
other >= 3 hours separation from other oral drugs → caution (continue; patiromer)
“Administer Veltassa at least 3 hours before or 3 hours after other oral medications except those shown to not have a clinically important interaction [see Drug Interactions (7) and Clinical Pharmacology (12.3)].” — fda-patiromer, Section 2.1 General Information
other >= 2 hours separation from other oral drugs → caution (continue; sodium-zirconium-cyclosilicate)
“In general, other oral medications should be administered at least 2 hours before or 2 hours after LOKELMA [see Drug Interactions (7) ].” — fda-sodium-zirconium-cyclosilicate, Section 2.3 Reconstitution and Administration
egfr < 30 mL/min/1.73m2 → allowed (initiate; patiromer, sodium-zirconium-cyclosilicate)
“Patients were excluded if they had an estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m2, systolic blood pressure <90 mmHg or symptomatic hypotension, or any significant comorbidity that could change their clinical course independent of heart failure.” — butler2022, Methods (Patients)

Trial evidence (informational)

DIAMOND · HFrEF (LVEF ≤40%) with RAASi hyperkalaemia (two K >5.0) or prior RAASi reduction; eGFR ≥30
Adjusted mean change in K (primary): +0.03 vs +0.13 mmol/L; difference −0.10 mmol/L, P<0.001
“At the end of treatment, the median (interquartile range) duration of follow-up was 27 (13–43) weeks, the adjusted mean change in potassium was +0.03 mmol/l in the patiromer group and +0.13 mmol/l in the placebo group [difference in the adjusted mean change between patiromer and placebo: −0.10 mmol/l (95% confidence interval, CI −0.13, 0.07); P < 0.001].” — butler2022, Abstract (Methods and results)
DIAMOND · as above
Hyperkalaemia >5.5 / MRA dose reduction: HR 0.63 (0.45-0.87) / HR 0.62 (0.45-0.87)
“Risk of hyperkalemia >5.5 mmol/l [hazard ratio (HR) 0.63; 95% CI 0.45, 0.87; P = 0.006), reduction of MRA dose (HR 0.62; 95% CI 0.45, 0.87; P = 0.006), and total adjusted hyperkalemia events/100 person-years (77.7 vs. 118.2; HR 0.66; 95% CI 0.53, 0.81; P < 0.001) were lower with patiromer.” — butler2022, Abstract (Methods and results)
REALIZE-K · HFrEF (LVEF ≤40%), MRA-induced hyperkalaemia, eGFR ≥30 (randomized withdrawal, n=203)
Optimal response (normokalaemia on spironolactone ≥25 mg): 71% vs 36%; OR 4.45 (2.89-6.86)
“Higher percentage of SZC- vs placebo-treated participants had optimal response (71% vs 36%; OR: 4.45; 95% CI: 2.89-6.86; P < 0.001).” — kosiborod2025, Abstract (Results)
REALIZE-K · as above
CV death or worsening HF (exploratory): 11 (11%) SZC vs 3 (3%) placebo; nominal P=0.034
“Composite of cardiovascular (CV) death or worsening HF occurred in 11 (11%) participants in the SZC group (1 with CV death, 10 with HF events) and 3 (3%) participants in the placebo group (1 with CV death, 2 with HF events; log-rank nominal P = 0.034).” — kosiborod2025, Abstract (Results)
PRIORITIZE-HF · Symptomatic HFrEF at hyperkalaemia risk (eGFR 20-59), n=182, terminated early (COVID-19)
RAASi intensity categories at 12 weeks: No significant difference (P=0.43)
“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).” — tardif2023, Abstract (Methods and results)
DIALIZE · 196 HD patients with predialysis hyperkalaemia
Responders (predialysis K 4.0-5.0 in ≥3/4 sessions): 41.2% vs 1.0%, P<0.001
“Of 97 patients receiving sodium zirconium cyclosilicate, 41.2% met the primary end point and were deemed treatment responders compared with 1.0% of 99 patients receiving placebo (P<0.001).” — fishbane2019, Abstract (Results)
DIALIZE-Outcomes · 2690 HD patients with predialysis K ≥5.5
SCD, stroke, arrhythmia-related events: 8.8% vs 8.9%; HR 0.98 (0.76-1.26)
“No treatment effect was observed on the primary composite end point (SZC, 8.8% [119 patients] vs. placebo, 8.9% [119 patients]; hazard ratio 0.98; 95% confidence interval 0.76-1.26) or individual cardiovascular outcomes.” — fishbane2025, Abstract (Results)
PEARL-HD · ESKD on thrice-weekly HD (n=31 analysed)
Episodes of K ≥5.5: Fewer hyperkalaemia episodes with patiromer
“Patiromer administered daily reduced the frequency of hyperkalemia in study participants with ESKD who receive thrice-weekly HD. Larger studies are needed to determine whether patiromer reduces significant cardiac events.” — middleton2024, Abstract (Conclusion)

Acute kidney injury

“Limitation of Use: Veltassa should not be used as an emergency treatment for life-threatening hyperkalemia because of its delayed onset of action [see Clinical Pharmacology (12.2)].”
VELTASSA (patiromer) PI, Vifor (2025)· Section 1 Indications and Usage Source
“LOKELMA should not be used as an emergency treatment for life-threatening hyperkalemia because of its delayed onset of action [see Clinical Pharmacology (12.2) and Clinical Studies (14)].”
LOKELMA (sodium zirconium cyclosilicate) PI, AstraZeneca (2025)· Section 1 Indications and Usage Source
“Importantly, insulin-dextrose infusions do not result in any potassium excretion, so severe and refractory hyperkalaemia in patients with severely decreased GFR or low urine output may need emergent dialysis.”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 19 Source
“Severe hyperkalaemia can result in life-threatening arrhythmias, particularly when serum potassium is >6.5 mmol/L.”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 19 Source

Dialysis

Trials: DIALIZE, DIALIZE-Outcomes

“For patients on chronic hemodialysis, administer LOKELMA only on non-dialysis days.”
LOKELMA (sodium zirconium cyclosilicate) PI, AstraZeneca (2025)· Section 2.2 Dosage Adjustment for Patients on Chronic Hemodialysis Source
“The recommended starting dose is 5 g once daily on non-dialysis days. Consider a starting dose of 10 g once daily on non-dialysis days in patients with serum potassium greater than 6.5 mEq/L.”
LOKELMA (sodium zirconium cyclosilicate) PI, AstraZeneca (2025)· Section 2.2 Dosage Adjustment for Patients on Chronic Hemodialysis Source
“A greater proportion of patients were responders in the LOKELMA arm as compared to placebo (41% vs 1%, respectively; p<0.001).”
LOKELMA (sodium zirconium cyclosilicate) PI, AstraZeneca (2025)· Section 14.5 Study 4 Source
“In a clinical trial of LOKELMA in patients on chronic hemodialysis in which most patients were treated with doses of 5 to 10 g once daily on non-dialysis days, there was no difference in the mean change from baseline in interdialytic weight gain (a measure of fluid retention) between the LOKELMA and placebo groups.”
LOKELMA (sodium zirconium cyclosilicate) PI, AstraZeneca (2025)· Section 5.2 Edema Source
“In a clinical trial of LOKELMA in patients on chronic hemodialysis, 5% of patients developed pre-dialysis hypokalemia (serum potassium <3.5 mEq/L) in both the LOKELMA and placebo groups; 3% and 1% of patients developed a serum potassium < 3.0 mEq/L in the LOKELMA and placebo groups, respectively.”
LOKELMA (sodium zirconium cyclosilicate) PI, AstraZeneca (2025)· Section 6.1 Laboratory Abnormalities Source
“Of 97 patients receiving sodium zirconium cyclosilicate, 41.2% met the primary end point and were deemed treatment responders compared with 1.0% of 99 patients receiving placebo (P<0.001).”
Fishbane S et al. DIALIZE: sodium zirconium cyclosilicate in hemodialysis. J Am Soc Nephrol 2019 (PMC6727265) (2019)· Abstract (Results) Source
“No treatment effect was observed on the primary composite end point (SZC, 8.8% [119 patients] vs. placebo, 8.9% [119 patients]; hazard ratio 0.98; 95% confidence interval 0.76-1.26) or individual cardiovascular outcomes.”
Fishbane S et al. DIALIZE-Outcomes. Kidney Int 2025 (PMID 40618849, abstract) (2025)· Abstract (Results) Source
“Maintenance of normokalemia at 12 months was significantly better with SZC than placebo (74.0% [495 patients] vs. 47.0% [293 patients]; odds ratio 3.36; 95% confidence interval 2.64-4.26).”
Fishbane S et al. DIALIZE-Outcomes. Kidney Int 2025 (PMID 40618849, abstract) (2025)· Abstract (Results) Source
“Patiromer administered daily reduced the frequency of hyperkalemia in study participants with ESKD who receive thrice-weekly HD. Larger studies are needed to determine whether patiromer reduces significant cardiac events.”
Middleton JP et al. Randomized trial of patiromer on efficacy to reduce episodic hyperkalemia in patients with ESKD treated with hemodialysis (PEARL-HD). Kidney Int Rep 2024 (PMC11551111, full text) (2024)· Abstract (Conclusion) Source
“Minimize electrolyte shifts and avoid sudden cardiac death • Dietary potassium restriction • Potassium binders • Titrate dialysate prescription”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 68 Source
“The effect of oral potassium binders on clinical outcomes in HF has not been established.”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 39, Section 6.2.3.2 Source

Kidney transplant

“In another drug-drug interaction study in healthy volunteers, co-administration of LOKELMA 15 g decreased the systemic exposures of tacrolimus (Figure 2), likely due to LOKELMA’s action on elevating gastric pH.”
LOKELMA (sodium zirconium cyclosilicate) PI, AstraZeneca (2025)· Section 12.3 Pharmacokinetics (Drug Interactions) Source
“Immunosuppressants Mycophenolate mofetil”
VELTASSA (patiromer) PI, Vifor (2025)· Section 7.1, Table 2 Source
“Immunosuppressants Tacrolimus”
VELTASSA (patiromer) PI, Vifor (2025)· Section 7.2, Table 3 Source
“The utilization of oral potassium binders can minimize the additional risk of hyperkalemia from using RASi and MRA and facilitate more permanent use of GDMT.”
Ghimire A et al. Heart Failure in Kidney Transplant Recipients: Narrative Review of Risk Factors, Therapy, and Current Gaps. Cardiol Ther 2026 (PMC12988941) (2026)· Strategies to enhance GDMT uptake Source

Albuminuria

No albuminuria-specific binder statement. KDIGO 2024 frames binders as a way to keep RASi in CKD (where RASi is indicated for A2-A3).

“Practice Point 3.6.3: Hyperkalemia associated with use of RASi can often be managed by measures to reduce the serum potassium levels rather than decreasing the dose or stopping RASi.”
KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of CKD (2024)· p. 44 Source
“Use of these newer exchange agents may help facilitate essential use of RASi/MRA.”
KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of CKD (2024)· p. 111 Source

Monitoring

“Adults: The recommended starting dose of Veltassa is 8.4 grams patiromer orally once daily. The dose can be up-titrated based on serum potassium level at 1-week or longer intervals, in increments of 8.4 grams.”
VELTASSA (patiromer) PI, Vifor (2025)· Section 2.2 Recommended Dosing and Titration Source
“During initiation and after a dose adjustment, assess serum potassium after one week. The recommended maintenance dose range is from 5 g to 15 g once daily, on non-dialysis days.”
LOKELMA (sodium zirconium cyclosilicate) PI, AstraZeneca (2025)· Section 2.2 Dosage Adjustment for Patients on Chronic Hemodialysis Source
“Monitor serum magnesium. Consider magnesium supplementation in patients who develop low serum magnesium levels on Veltassa.”
VELTASSA (patiromer) PI, Vifor (2025)· Section 5.2 Hypomagnesemia Source
“Monitor for signs of edema, particularly in patients who should restrict their sodium intake or are prone to fluid overload (e.g., heart failure or renal disease). Advise patients to adjust dietary sodium, if appropriate.”
LOKELMA (sodium zirconium cyclosilicate) PI, AstraZeneca (2025)· Section 5.2 Edema Source
“Practice Point 3.6.2: Changes in BP, serum creatinine, and serum potassium should be checked within 2–4 weeks of initiation or increase in the dose of a RASi, depending on the current GFR and serum potassium.”
KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of CKD (2024)· p. 44 Source

In-hospital initiation

“LOKELMA should not be used as an emergency treatment for life-threatening hyperkalemia because of its delayed onset of action [see Clinical Pharmacology (12.2) and Clinical Studies (14)].”
LOKELMA (sodium zirconium cyclosilicate) PI, AstraZeneca (2025)· Section 1 Indications and Usage Source
“For initial treatment of hyperkalemia, the recommended dose of LOKELMA is 10 g administered three times a day for up to 48 hours.”
LOKELMA (sodium zirconium cyclosilicate) PI, AstraZeneca (2025)· Section 2.1 Recommended Dosage Source
“Importantly, insulin-dextrose infusions do not result in any potassium excretion, so severe and refractory hyperkalaemia in patients with severely decreased GFR or low urine output may need emergent dialysis.”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 19 Source

Outpatient

Main use is chronic outpatient RAASi/MRA enablement (DIAMOND, REALIZE-K run-in). ESC 2026 makes no recommendation; ACC 2024 says 'consider'; KDIGO 2024 puts binders before reducing RASi/MRA.

“No specific recommendations for the use of potassium binders are included in the guideline at current time, due to insufficient evidence for clinical benefit.”
2026 ESC Guidelines for the diagnosis and treatment of heart failure (2026)· p. 33 Source
“Consider treating with patiromer or sodium zirconium cyclosilicate”
2024 ACC Expert Consensus Decision Pathway for Treatment of HFrEF (2024)· p. 31 Source
“2nd line: Medications Consider: • Appropriate use of diuretics • Optimize serum bicarbonate levels • Licensed potassium exchange agents 3rd line: Last resort • Reduce dose or discontinue RASi/MRA”
KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of CKD (2024)· p. 113 Source
“Patiromer allowed for 85% of participants to be optimized on GDMT.”
2024 ACC Expert Consensus Decision Pathway for Treatment of HFrEF (2024)· p. 18 Source

Where sources disagree

Should binders be used to enable RAASi/MRA in HF (recommendation strength)?

“No specific recommendations for the use of potassium binders are included in the guideline at current time, due to insufficient evidence for clinical benefit.”
2026 ESC Guidelines for the diagnosis and treatment of heart failure (2026)· p. 33 Source
“In patients with HF who experience hyperkalemia (serum potassium level ‡5.5 mEq/L) while taking a renin-angiotensin-aldosterone system inhibitor (RAASi), the effectiveness of potassium binders (patiromer, sodium zirconium cyclosilicate) to improve outcomes by facilitating continuation of RAASi therapy is uncertain (5,6).”
2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure (2022)· p. 48 Source
“Treatment with oral potassium binders (patiromer or sodium zirconium cyclosilicate) may be useful in patients with HF and CKD to decrease serum potassium, reduce the risk of hyperkalaemia, and avoid down-titration or withdrawal of risk-modifying therapies such as ACEI/ARBs, ARNIs, and MRAs.”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 39 Source
“2nd line: Medications Consider: • Appropriate use of diuretics • Optimize serum bicarbonate levels • Licensed potassium exchange agents 3rd line: Last resort • Reduce dose or discontinue RASi/MRA”
KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of CKD (2024)· p. 113 Source
“Consider treating with patiromer or sodium zirconium cyclosilicate”
2024 ACC Expert Consensus Decision Pathway for Treatment of HFrEF (2024)· p. 31 Source
“In patients with chronic or recurrent hyperkalaemia on RAAS inhibitors therapy an approved Kþ-lowering agent may be initiated as soon as Kþ levels are confirmed as >5.0 mEq/L.”
2021 ESC HF Guidelines Supplementary Data (2021)· p. 35 Source

Potassium threshold at which to start a binder / act on RAASi

“In patients with chronic or recurrent hyperkalaemia on RAAS inhibitors therapy an approved Kþ-lowering agent may be initiated as soon as Kþ levels are confirmed as >5.0 mEq/L.”
2021 ESC HF Guidelines Supplementary Data (2021)· p. 35 Source
“The protocol required patients to have hyperkalemia at screening (defined as two serum potassium values of >5.0 mmol/l) while receiving an angiotensin-converting enzyme inhibitor (ACEi), angiotensin receptor blocker (ARB), angiotensin receptor-neprilysin inhibitor (ARNi), and/or MRA therapy.”
Butler J, Anker SD, Lund LH, et al. Patiromer for the management of hyperkalemia in HFrEF: the DIAMOND trial. Eur Heart J 2022;43:4362-73 (PMC9622299, full text) (2022)· Methods (Patients) Source
“Figure 32 | Actions to manage hyperkalemia (potassium >5.5 mmol/l) in chronic kidney disease.”
KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of CKD (2024)· p. 113 Source
“A conservative threshold for action is recurrent serum potassium values >5.5 mmol/L.”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 19 Source
“Higher thresholds for action (e.g. >5.7 mmol/L) are often justified in CKD due to chronic hyperkalaemia, aiming to avoid serum potassium levels of 6.0 mmol/L or above.”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 19 Source
“Severe hyperkalaemia (potassium >5.5 or >6 mmol/L) should lead to temporary down-titration or discontinuation of MRAs and/or ARNIs/ACE-Is/ARBs (see Supplementary data online, Tables S4, S5 and S9).”
2026 ESC Guidelines for the diagnosis and treatment of heart failure (2026)· p. 35 Source
“Stop ACEI/ARB/finerenone if potassium ≥6.0 mmol/L; in 5.5–6.0 mmol/L range, should optimize other factors and consider dose reduction, where applicable (Section 3.7.1).”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 33 Source
“Generally, dose reduction of these agents is advised if potassium is between 5.5 mEq/L and 6 mEq/L and temporarily termination if potassium is above 6 mEq/L, with reinstitution of the drug only when the potassium drops below 5.5 mEq/L.”
Mullens 2022 EJHF: Renal effects of GDMT in HF, HFA/ESC consensus statement (2022)· p. 13 Source

SZC sodium load, oedema and HF events

“In the REALIZE-K trial, there was a signal towards more HF deterioration with sodium zirconium cyclosilicate as compared with placebo, although the trial was not powered to detect clinical outcomes.”
2026 ESC Guidelines for the diagnosis and treatment of heart failure (2026)· p. 33 Source
“Although underpowered for clinical outcomes, more participants had HF events with SZC than placebo, which should be factored into the clinical decision making.”
Kosiborod MN et al. Sodium zirconium cyclosilicate for management of hyperkalemia during spironolactone optimization in patients with heart failure (REALIZE-K). J Am Coll Cardiol 2025;85:971-984 (PubMed abstract, PMID 39566872) (2025)· Abstract (Conclusions) Source
“Monitor for signs of edema, particularly in patients who should restrict their sodium intake or are prone to fluid overload (e.g., heart failure or renal disease). Advise patients to adjust dietary sodium, if appropriate.”
LOKELMA (sodium zirconium cyclosilicate) PI, AstraZeneca (2025)· Section 5.2 Edema Source
“Risks of HHF (any/primary) (adjusted hazard ratios [HRs], 1.373; 95% confidence interval [CI], 1.337 to 1.410), major edema encounter (HR, 1.330; 95% CI, 1.298 to 1.363), and death (HR, 1.287; 95% CI, 1.255 to 1.320) were also significantly higher in the SZC cohort compared with the PAT cohort (P < 0.05).”
Desai NR et al. The association of heart failure and edema events between patients initiating SZC or patiromer. Kidney360 2024;5:1835-1843 (PMC11687973, full text; CSL Vifor-funded claims analysis) (2024)· Abstract (Results) Source
“In a clinical trial of LOKELMA in patients on chronic hemodialysis in which most patients were treated with doses of 5 to 10 g once daily on non-dialysis days, there was no difference in the mean change from baseline in interdialytic weight gain (a measure of fluid retention) between the LOKELMA and placebo groups.”
LOKELMA (sodium zirconium cyclosilicate) PI, AstraZeneca (2025)· Section 5.2 Edema Source
“At the end of the open‐label phase, 11.6% of patients remained hyperkalaemic (sK+ >5.0 mEq/L) despite SZC titration; 1.1% had experienced an oedema‐related adverse event.”
Petrie MC et al. SZC, hyperkalaemia, and spironolactone optimization in HFrEF: the REALIZE-K open-label run-in phase. Eur J Heart Fail 2025 (PMC12482837, full text) (2025)· Results (Cohort 1) Source

Dialysis use: SZC labelled vs patiromer not labelled

“For patients on chronic hemodialysis, administer LOKELMA only on non-dialysis days.”
LOKELMA (sodium zirconium cyclosilicate) PI, AstraZeneca (2025)· Section 2.2 Dosage Adjustment for Patients on Chronic Hemodialysis Source
“No special dosing adjustments are needed for patients with renal impairment.”
VELTASSA (patiromer) PI, Vifor (2025)· Section 8.6 Renal Impairment Source
“Patiromer administered daily reduced the frequency of hyperkalemia in study participants with ESKD who receive thrice-weekly HD. Larger studies are needed to determine whether patiromer reduces significant cardiac events.”
Middleton JP et al. Randomized trial of patiromer on efficacy to reduce episodic hyperkalemia in patients with ESKD treated with hemodialysis (PEARL-HD). Kidney Int Rep 2024 (PMC11551111, full text) (2024)· Abstract (Conclusion) Source
“No treatment effect was observed on the primary composite end point (SZC, 8.8% [119 patients] vs. placebo, 8.9% [119 patients]; hazard ratio 0.98; 95% confidence interval 0.76-1.26) or individual cardiovascular outcomes.”
Fishbane S et al. DIALIZE-Outcomes. Kidney Int 2025 (PMID 40618849, abstract) (2025)· Abstract (Results) Source

HF trial evidence below eGFR 30 vs label permission

“Patients were excluded if they had an estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m2, systolic blood pressure <90 mmHg or symptomatic hypotension, or any significant comorbidity that could change their clinical course independent of heart failure.”
Butler J, Anker SD, Lund LH, et al. Patiromer for the management of hyperkalemia in HFrEF: the DIAMOND trial. Eur Heart J 2022;43:4362-73 (PMC9622299, full text) (2022)· Methods (Patients) Source
“prevalent hyperkalaemia (Cohort 1), defined as sK+ 5.1–5.9 mEq/L at screening and estimated glomerular filtration rate (eGFR) ≥30 ml/min/1.73 m2”
Petrie MC et al. SZC, hyperkalaemia, and spironolactone optimization in HFrEF: the REALIZE-K open-label run-in phase. Eur J Heart Fail 2025 (PMC12482837, full text) (2025)· Methods Source
“estimated glomerular filtration rate (eGFR) 20 to 44 mL/min/1.73 m2 [calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) equation] and serum potassium concentration between 4.0 and 5.5 mmol/L”
Tardif JC et al. Potassium reduction with sodium zirconium cyclosilicate in patients with heart failure (PRIORITIZE-HF). ESC Heart Fail 2023;10:1066-1076 (PMC10053160, full text) (2023)· Methods (Study population) Source
“Of the 666 adult patients treated with Veltassa in clinical studies, 93% had chronic kidney disease (CKD).”
VELTASSA (patiromer) PI, Vifor (2025)· Section 8.6 Renal Impairment Source
“However, due to the trial exclusion criteria, only 43 patients had an eGFR <30 ml/min/1.73 m2 [82].”
Bergen K, Spaak J. What to do with key cardiovascular drugs when kidney function worsens? Clin Kidney J 2026;19:sfaf354 (PMC12793518, full text) (2026)· Potassium binders section Source

Open questions

Should the tool suggest a binder automatically when K exceeds the RAASi hold threshold, given ESC 2026 HF makes no recommendation? Proposed: show as an optional 'consider' with the REALIZE-K HF-event caveat for SZC.
Default K threshold for 'consider binder' (5.0 vs 5.5 vs 5.7) needs an owner decision; all are sourced.
Beta-blocker spacing: the patiromer label requires 3-h separation from bisoprolol, carvedilol and nebivolol (the HF beta-blockers). Should this appear as an interaction note in the beta-blocker profile?
Sodium polystyrene sulfonate is mentioned by ESC CVD-CKD (cost alternative, no randomized data) and is outside this class file. Include it?
No EMA SmPC was fetched (FDA labels exist for both). The EU Lokelma SmPC also has a dialysis regimen; fetch it if EU-specific wording is wanted.