Is there evidence to support the use of sodium zirconium cyclosilicate (Lokelma®) or patiromer (Veltassa®) over sodium polystyrene (Kayexalate®) for the treatment of acute hyperkalemia in hospitalized patients?

Comment by InpharmD Researcher

Limited head-to-head data are available comparing the use of sodium zirconium cyclosilicate (Lokelma®), patiromer (Veltassa®), and sodium polystyrene (Kayexalate®) in the setting of acute hyperkalemia; most studies focus on chronic/outpatient use. One retrospective study compared patiromer to sodium polystyrene in which sodium polystyrene demonstrated a significant reduction in potassium over patiromer in mildly hyperkalemic patients. There appears to be a lack of safety data comparing the three agents.

Background

Sodium zirconium cyclosilicate (SZC) is shown to be effective in reducing serum potassium in observed clinical trials. The effects of reducing hyperkalemic levels are normally reported to occur within 48 hours but can substantially decrease measured potassium levels as early as 1 hour. Whether patients can be safely discharged after achieving such levels, however, is uncertain. Reduction in potassium levels can be maintained as long as 28 days according to one study [Table 5] and there are extended studies that have documented over 3 to 12 months of sustained benefits. Evidence for sustained normokalemic levels is limited as most studies only observe patients from 2 to 4 weeks. [1], [2], [3]

Before modern agents, sodium polystyrene sulfonate (SPS; Kayexalate) had been the lone treatment option for hyperkalemia for over 50 years; however, It has shown untoward gastrointestinal (GI) effects ranging from nausea and diarrhea to mucosal damage and intestinal necrosis. SPS can also cause various electrolyte abnormalities including hypernatremia, hypocalcemia, and hypomagnesemia. [4]

A 2017 review and meta-analysis compared patiromer and SZC in the treatment of hyperkalemia. In their analysis at day 3 of patiromer treatment, potassium change was -0.36 mEq/L (range of standard deviation 0.07 to 0.30). At 48 hours for SZC was -0.67 mEq/L (95% CI -0.45 to -0.89 mEq/L). At 1 hour, SZC change in potassium was -0.17 mEq/L (95% CI -0.05 to -0.30). Pooled analysis on adverse effects showed patiromer was associated with more gastrointestinal upset (7.6% constipation, 4.5% diarrhea) and electrolyte depletion (7.1% hypomagnesemia), whereas SZC was associated with adverse effects of urinary tract infections (1.1%) and edema (0.9%). The authors concluded, “both agents exhibited statistically and clinically significant reductions in potassium. Given the adverse effect profile and the observed time-dependent effects, sodium zirconium cyclosilicate may play more of a role in treating acute hyperkalemia.” However, these conclusions are limited by a lack of direct comparative data including similarly timed measurements. [4]

Literature Review

A search of the published medical literature revealed 5 studies investigating the researchable question:

Please see Tables 1-5 for your response.

Emergency Potassium Normalization Treatment Including Sodium Zirconium Cyclosilicate: A Phase II, Randomized, Double-blind, Placebo-controlled Study (ENERGIZE)
Design	Exploratory, phase II, multicenter, randomized, double-blind, placebo-controlled study N= 70
Objective	To perform a pilot evaluation to determine the efficacy of sodium zirconium cyclosilicate (SZC) combined with insulin and glucose for the emergency treatment of hyperkalemia.
Study Groups	SZC 10 g (n= 33) Placebo (n= 37)
Inclusion Criteria	Age > 18 years, admitted to the ED, potassium levels > 5.8 mmol/L measured by a point-of-care i-STAT device
Exclusion Criteria	Pseudohyperkalemia, life-threatening cardiac arrhythmia, expected dialysis within 4 hours of randomization, other indications requiring immediate hospital treatment, other causes of hyperkalemia that would benefit from another treatment, pregnancy/breastfeeding
Methods	Patients were randomized (1:1) to receive SZC 10 g PO up to three times during a 10-hour period at approximately 1, 4, and 10 hours or matching placebo. All patients received insulin weight-based dosing plus glucose (modified from guideline recommendations to reduce the risk of hypoglycemia). Additional potassium-lowering medications may have been given as necessary (e.g. repeat insulin/glucose). Patients initiated on dialysis were immediately discontinued from further study treatment. A post hoc analysis was performed to find the adjusted least-squares (LS) mean difference in each treatment group. The LS mean analysis will attempt to adjust for disparities in the baseline characteristics that might influence the results. The baseline characteristics of interest were not specified.
Duration	8 days
Outcome Measures	Primary outcome: reduction of serum potassium (sK+) at 4 hours versus baseline
Baseline Characteristics		SZC (n= 33)	Placebo (n= 37)
	Age, years	62.0 ± 12.7	56.4 ± 14.4
	Female	16 (48.5%)	19 (51.4%)
	Race White Black Asian Other	22 (66.7%) 11 (33.3%) 0 0	26 (70.3%) 9 (24.3%) 1 (2.7%) 1 (2.7%)
	Hispanic or latino	6 (18.2%)	19 (27.0%)
	Serum potassium	6.38 ± 0.63	6.48 ± 0.76
Results	Endpoint	SZC (n=33)	Placebo (n=37)
	Reduction in mean serum potassium at 4 hours versus baseline, mmol/L Difference in LS mean (95% confidence interval [CI])	-0.36 ± 0.57 -0.13 (-0.44 to 0.17)	-0.25 ± 0.63 -
	LS mean difference in serum potassium versus baseline, mmol/L (95% CI) Difference in least squares mean (95% CI)	-0.41 (-0.63 to -0.19) -0.13 (-0.44 to 0.17)	-0.27 (-0.48 to -0.07) -
Adverse Events	Any AE within 24 hours after starting dose SZC 24.1% versus placebo 27.3% Any AE occurring 24 hours after starting dose SZC 24.1% versus placebo 9.1% No incidence of hypokalemia reported Hypoglycemia (glucose < 70 mg/dL) was reported in 55.2% in the SZC group and 40.6% in the placebo group
Study Author Conclusions	This pilot study suggested that SZC with insulin and glucose may provide an incremental benefit in the emergency treatment of hyperkalemia over insulin and glucose alone.
InpharmD Researcher Critique	The study was performed in Denmark which may not reflect the U.S. population. This was the earliest known study for SZC which served as exploratory data for subsequent trials. Missing central potassium levels were substituted with adjusted i-STAT data.

References:

Peacock WF, Rafique Z, Vishnevskiy K, et al. Emergency potassium normalization treatment including sodium zirconium cyclosilicate: a phase II, randomized, double-blind, placebocontrolled study (ENERGIZE). Acad Emerg Med. 2020;27(6): 475-486.

Effect of Sodium Zirconium Cyclosilicate on Potassium Lowering for 28 Days Among Outpatients With Hyperkalemia (The HARMONIZE Randomized Clinical Trial)
Design	Phase 3, multicenter, randomized, double-blind, placebo-controlled trial N=258
Objective	To evaluate the efficacy and safety of sodium zirconium cyclosilicate (SZC) for 28 days in patients with hyperkalemia
Study Groups	SZC 5 g (n=45) SZC 10 g (n=51) SZC 15 g (n=56) Placebo (n=85)
Inclusion Criteria	Patients ≥ 18 years of age, having hyperkalemia (2 consecutive potassium values, measured 60 minutes apart, both ≥ 5.1 mEq/L), being able to have repeated blood draws
Exclusion Criteria	Patients with pseudohyperkalemia, dialysis requirement, life expectancy less than 3 months, cardiac arrhythmias, diabetic ketoacidosis, active treatment with sodium polystyrene sulfonate or lactulose, prior participation in another zirconium cyclosilicate trial or treatment with an unapproved drug or device within 30 days of starting the study
Methods	The study was divided into two phases: an open-label phase and the randomized phase. In the open-label phase, patients received 10 g of zirconium cyclosilicate 3 times daily with meals for 48 hours (6 total doses). If patients achieved normokalemia at the end of the open-label phase, then patients were randomized (4:4:4:7) to receive SZS 5 g, 10 g, 15 g, or placebo once daily. The dose was reduced from once daily to every other day for the remainder of the study if a patient’s potassium value was between 3.0 and 3.4 mEq/L at any time during the randomized phase.
Duration	29 days (open-label phase 48 hours)
Outcome Measures	Primary outcome: the comparison of mean serum potassium levels between placebo and each treatment group during days 8 through day 29 Secondary outcome: proportion of patients who were normokalemic at end of study, time to first recurrence of hyperkalemia, mean change in serum aldosterone and plasma renin between open-label phase baseline and day 29
Baseline Characteristics		SZC 5 g (n=45)	SZC 10 g (n=51)	SZC 15 g (n=56)	Placebo (n=85)
	Age, years	61.5 ± 16.9	63.8 ± 10	64.9 ± 12.9	64.3 ± 12.1
	Female	18 (40%)	24 (47.1%)	16 (28.6%)	41 (48.2%)
	White	36 (80%)	44 (86.3%)	46 (82.1%)	73 (85.9%)
	Serum potassium, mg/dL	4.5 ± 0.4	4.4 ± 0.4	4.5 ± 0.4	4.6 ± 0.4
	Comorbidities Chronic kidney disease Heart failure Diabetes mellitus	29 (64.4%) 18 (40%) 26 (57.8%)	36 (70.6%) 18 (35.3%) 38 (74.5%)	37 (66.1%) 25 (44.6%) 39 (69.6%)	50 (58.8%) 26 (30.6%) 54 (63.5%)
	Renin-angiotensin-aldosterone system inhibitors	33 (73.3%)	36 (70.6%)	33 (58.9%)	61 (71.8%)
Results	Endpoint	SZC 5 g (n=45)	SZC 10 g (n=51)	SZC 15 g (n=56)	Placebo (n=82)
	Potassium days 8 to 29, (95% confidence interval [CI]), mEq/L p-value versus placebo	4.8 (4.6 to 4.9) p<0.001	4.5 (4.4 to 4.6) p<0.001	4.4 (4.3 to 4.5) p<0.001	5.1 (5.0 to 5.2) -
	Proportion of normokalemic patients At day 15 At day 29	31/44 (70.5%) 32/45 (71.1%)	40/47 (85.1%) 38/50 (76.0%)	43/52 (82.7%) 45/54 (85.2%)	35/80 (43.8%) 39/82 (47.6%)
	Time to first hyperkalemia, day	14 (p=0.002)	28 (p<0.001)	Not reached	7
	Change in serum aldosterone (95% CI), ng/dL	–4.8 (–7.8 to –1.9)	–6.1 (–10.1 to –2.1)	–3.7 (–5.8 to –1.6)	–0.8 (–2.1 to 0.5)
Adverse Events	Common Adverse Events	SZC 5 g (n=45)	SZC 10 g (n=51)	SZC 15 g (n=56)	Placebo (n=82)
	Any events Anemia Edema Hypokalemia Nasopharyngitis	24 (53.3%) 0 1 (2.2%) 0 0	15 (29.4%) 0 3 (5.9%) 5 (9.8%) 0	25 (44.6%) 3 (5.4%) 8 (14.3%) 6 (10.7%) 3 (5.4%)	27 (31.8%) 0 0 0 1 (1.2%)
	Any serious event Cardiac failure Myocardial infarction Hepatotoxicity Pneumonia Dyspnea	5 (11.1%) 0 1 (2.2%) 1 (2.2%) 1 (2.2%) 0	2 (3.9%) 1 (2.0%) 0 0 0 0	3 (5.4%) 0 0 0 1 (1.8%) 1 (1.8%)	0 0 0 0 0 0
Study Author Conclusions	Among outpatients with hyperkalemia, open-label sodium zirconium cyclosilicate reduced serum potassium to normal levels within 48 hours; compared with placebo, all three doses of zirconium cyclosilicate resulted in lower potassium levels and a higher proportion of patients with normal potassium levels for up to 28 days. Further studies are needed to evaluate the efficacy and safety of zirconium cyclosilicate beyond 4 weeks and to assess long-term clinical outcomes.
InpharmD Researcher Critique	The study outcome was limited due to excluding hospitalized patients and those with life-threatening arrhythmias. The exclusion criteria is extensive and may limit the generalizability of the study. Follow-up was limited to 28 days of therapy

References:

Kosiborod M, Rasmussen HS, Lavin P, et al. Effect of sodium zirconium cyclosilicate on potassium lowering for 28 days among outpatients with hyperkalemia: the harmonize randomized clinical trial. JAMA 2014;312:2223–2233.

Sodium Zirconium Cyclosilicate in Hyperkalemia
Design	Multicenter, two-stage, randomized, double-blind, phase 3 trial N=754 (initial phase) N=543 (maintenance phase)
Objective	To investigate whether sodium zirconium cyclosilicate (ZS-9), a novel selective cation exchanger, could lower serum potassium levels in patients with hyperkalemia
Study Groups	Initial phase: Placebo (n=158) 1.25 g ZS-9 (n=154) 2.5 g ZS-9 (n=141) 5 g ZS-9 (n=157) 10 g ZS-9 (n=143) Maintenance Phase: Placebo (n=216) 1.25 g ZS-9 (n=94) 2.5 g ZS-9 (n=104) 5 g ZS-9 (n=65) 10 g ZS-9 (n=63)
Inclusion Criteria	Patients ≥ 18 years old with a serum potassium of 5.0 to 6.5 mmol/L able to undergo repeated blood draws
Exclusion Criteria	Patients receiving dialysis or organic polymer resins, phosphate binders, lactulose, xifaxan, or other non-absorbed antibiotics for hyperammonemia within 1 week of enrollment; patients with diabetic ketoacidosis, a potassium level > 6.5 mmol/L, cardiac arrhythmia requiring immediate treatment, or pseudohyperkalmia signs and symptoms
Methods	The study was divided into two phases: a randomized initial and maintenance phase: Initial phase: Patients with mean serum potassium levels 5.0 to 6.5 mmol/L were randomized to receive 1.25 g, 2.5 g, 5 g, or 10 g of ZS-9 or placebo, all administered TID with meals for 48 hours. Maintenance phase: Once a serum potassium level of 3.5 to 4.9 mmol/L was achieved, patients were randomized (1:1) to receive their original ZS-9 dose or placebo daily for 28 days. Patients who were in the placebo group during the initial phase were randomized to receive 1.25 g or 2.5 g ZS-9.
Duration	28 days (48 hours for initial phase)
Outcome Measures	Primary outcome: Initial phase: between-group difference in exponential rate of change in mean serum potassium level during the first 48 hours Maintenance phase: between-group difference in mean serum potassium level during the 12-day treatment period following the initial phase
Baseline Characteristics		Placebo (n=158)	1.25 g ZS-9 (n=154)	2.5 g ZS-9 (n=141)	5 g ZS-9 (n=157)	10 g ZS-9 (n=143)
	Age, years	65.6 ± 12.2	65.4 ± 13.1	65.9 ± 11.7	65.2 ± 11.9	66.2 ± 12.2
	Male	98 (62%)	83 (53.9%)	91 (64.5%)	96 (61.1%)	80 (55.9%)
	Race White Black	136 (86.1%) 17 (10.8%)	131 (85.1%) 20 (13.0%)	125 (88.7%) 11 (7.8%)	132 (84.1%) 20 (12.7%)	120 (83.9%) 19 (13.3%)
	Baseline serum potassium 5.0-5.3 mmol/L 5.4-5.5 mmol/L 5.6-6.5 mmol/L	95 (60.1%) 22 (13.9%) 41 (25.9%)	76 (49.4%) 38 (24.7%) 40 (26%)	72 (51.1%) 29 (20.6%) 40 (28.4%)	90 (57.3%) 36 (22.9%) 31 (19.7%)	94 (65.7%) 27 (18.9%) 22 (15.4%)
	Medical history CKD Heart failure Diabetes mellitus Use of RAAS inhibitor	96 (60.8%) 66 (41.%) 96 (60.8%) 101 (63.9%)	102 (66.2%) 57 (37%) 94 (61%) 109 (70.8%)	89 (63.1%) 54 (38.3%) 84 (59.6%) 97 (68.8%)	93 (59.2%) 64 (40.8%) 96 (61.1%) 99 (63.1%)	83 (58%) 59 (41.3%) 81 (56.6%) 96 (67.1%)
	CKD: chronic kidney disease; RAAS: renin-angiotensin-aldosterone system *There was a significant difference for serum potassium levels at baseline for the overall comparison between the 5 study groups (p= 0.03).
Results	Endpoint	Placebo	1.25 g ZS-9	2.5 g ZS-9	5 g ZS-9	10 g ZS-9
	Initial phase Reduction in mean exponential rates of change/hour p-value	(n=158) 0.09% -	(n=154) 0.11% > 0.05	(n=141) 0.16% < 0.001	(n=157) 0.21% < 0.001	(n=143) 0.3% < 0.001
	Maintenance phase Increase in mean exponential rate of change/hour p-value	(n=216) 1.04% vs 10 g 0.47% vs 5 g	Not reported -	Not reported -	(n=65) 0.09% p=0.008	(n=63) 0.14% p<0.001
	The 5-g (p= 0.008) and 10-g (p < 0.001) groups were better in maintaining normokalemia compared to placebo during the maintenance phase.
Adverse Events	Common Adverse Events: Initial phase: gastrointestinal disorders (5.1% vs 4.5% vs 2.1% vs 3.8% vs 3.5%) Maintenance phase: gastrointestinal disorders (3.7% vs 4.2% vs 5.8% vs 7.7% vs 4.8%); urinary tract infeaction (1.4% vs 5.3% vs 1.9% vs 4.6% vs 1.6%)
	Serious Adverse Events: Two cases of hypokalemia were reported, one in the 2.5 g group and on in the 10-g group. One patient experienced atrial fibrillation in the 10 g group and one patient experienced atrial flutter in the 1.25 g group during the initial phase. During the initial phase, one patient experienced prolonged QTc interval in the 10 g group (an increase of 71 milliseconds to a QTc interval of 516 milliseconds). One patient in the placebo group and one in the 10 g group experienced atrial fibrillation, while one patient in the 2.5 g group experienced left bundle branch block during the maintenance phase.
	Percentage that Discontinued due to Adverse Events: Initial phase: (0.6% vs 1.3% vs 2.1% vs 0.6% vs 0.7%) Maintenance phase: (0.9% vs 1.1% vs 0 vs 1.5% vs 0)
Study Author Conclusions	ZS-9, as compared with placebo, was associated with a decrease in serum potassium levels within 48 hours after administration in a cohort of ambulatory patients with baseline potassium levels of 5.0 to 6.5 mmol per liter. In patients who continued to receive ZS-9, normokalemia was maintained for 14 days.
InpharmD Researcher Critique	This study is exclusive to the outpatient setting which may not reflect hospitalized patients with potential comorbidities that affect the rate of potassium clearance. While potassium levels seem to decrease significantly in a period of 48 hours with treatment of various doses, whether this drop is sufficient for therapy or the necessity for longer care is uncertain as this was a maintenance study.

References:

Packham DK, Rasmussen HS, Lavin PT, et al. Sodium zirconium cyclosilicate in hyperkalemia. N Engl J Med. 2015;372(3):222-231. doi:10.1056/NEJMoa1411487

Patiromer for Treatment of Hyperkalemia in the Emergency Department: A Pilot Study
Design	Single-center, randomized, open-label convenience sample pilot study N= 30
Objective	To investigate the potential efficacy and safety of oral patiromer in treating acute hyperkalemia in the emergency department (ED)
Study Groups	Standard of care (n= 15) Patiromer (n= 15)
Inclusion Criteria	Age ≥ 18, end-stage renal disease (ESRD), serum potassium ≥ 6.0 mEq/L, anticipated to wait for hemodialysis for at least 4 hours
Exclusion Criteria	Significant arrhythmia on electrocardiogram (ECG), known allergy to patiromer, administration of any potassium binder other than study drug, pregnancy
Methods	Patients were randomized to standard of care (SOC) or a single-dose of 25.2 g oral patiromer (PAT) plus standard of care. Patients were observed for up to 10 hours or until hemodialysis.
Duration	Observation: up to 10 hours
Outcome Measures	Primary: difference in adjusted mean serum potassium between SOC and PAT groups at 6 hours Secondary: differences between groups in the amount and number of dosages of insulin and albuterol given over 2, 4, and 6 hours
Baseline Characteristics		Standard of care (n= 15)		Patiromer (n= 15)
	Age, years (interquartile range [IQR])	48 (39.0-52.0)	n= 15	41 (36.0-50.0)	n= 15
	Female	8 (53.3%)	n= 15	5 (33.3%)	n= 15
	Potassium, mEq/L (standard deviation [SD])	6.7 (± 0.5)	n= 15	6.4 (± 0.5)	n= 15
	Magnesium, mg/dL (IQR)	2.8 (2.8-3.4)	n= 12	3.1 (2.7-3.4)	n= 13
	Glucose, mmol/L (IQR)	101 (92.0-112.0)	n= 15	116 (88.0-216.0)	n= 15
Results	Endpoint	Standard of care (n= 15)		Patiromer (n= 15)		p-Value
	Difference in serum potassium at 6 hours, mEq/L*	6.32		5.81		0.155
	Insulin given, IU (IQR) 2 hours 4 hours 6 hours	0 (0.0-5.0) 5 (0.0-5.0) 5 (0.0-10.0)	n= 15 n= 15 n= 10	0 (0.0-5.0) 0 (0.0-5.0) 5 (0.0-7.0)	n= 15 n= 15 n= 9	0.622 0.340 0.667
	Albuterol given, mg (IQR) 2 hours 4 hours 6 hours	0 (0.0-2.5) 2.5 (0.0-15.0) 12.5 (0.0-17.5)	n= 15 n= 15 n= 10	0 (0.0-0.0) 0 (0.0-2.5) 0 (0.0-10.0)	n= 15 n= 15 n= 9	0.654 0.141 0.097
	Number of interventions (IQR) 2 hours 4 hours 6 hours	0 (0.0-1.0) 1 (0.0-2.0) 2 (1.0-3.0)	n= 15 n= 15 n= 10	0 (0.0-1.0) 0 (0.0-2.0) 1 (0.0-2.0)	n= 15 n= 15 n= 9	1.000 0.232 0.237
	*Difference in serum potassium was significant at 2 hours, with mean serum potassium 6.51 mEq/L in SOC group versus 5.90 mEq/L in PAT group (p= 0.009).
Adverse Events	Common Adverse Events: gastrointestinal symptoms (nausea, vomiting, gastrointestinal discomfort) reported in 2 patients in SOC and 1 in PAT; hypoglycemia (blood glucose < 70 mg/dL) reported in 3 patients in SOC and 3 in PAT
	Serious Adverse Events: N/A
	Percentage that Discontinued due to Adverse Events: N/A
Study Author Conclusions	In this pilot study on the management of ED patients with acute severe hyperkalemia, a single dose of 25.2 g oral patiromer lowered the serum potassium within 2 hours but did not have a sustained effect at 6 hours compared to standard care. Our results are encouraging and support the need for a larger, definitive, multi-center study to establish the role of patiromer in the acute management of hyperkalemia.
InpharmD Researcher Critique	This was a small study with limited sample size, lack of blinding, and no power analysis. This is merely a hypothesis-generating pilot study.

References:

Rafique Z, Liu M, Staggers KA, Minard CG, Peacock WF. Patiromer for Treatment of Hyperkalemia in the Emergency Department: A Pilot Study. Acad Emerg Med. 2020;27(1):54-60. doi:10.1111/acem.13868

Comparison of Patiromer to Sodium Polystyrene Sulfonate in Acute Hyperkalemia
Design	Retrospective, single-center, quality improvement project N= 99
Objective	To compare the potassium reduction of patiromer to sodium polystyrene sulfonate (SPS) within 6 to 24 hours following a single dose
Study Groups	Patiromer (n= 49) SPS (n= 50)
Inclusion Criteria	Received 1 dose of either patiromer or SPS, had second potassium level drawn within 6 to 24 hours
Exclusion Criteria	Received more than 1 dose of study drug within 24 hours, received both study drugs within 24 hours, received fludrocortisone within 24 hours, underwent hemodialysis for hyperkalemia, diagnosis of acute kidney injury
Methods	Patient data charts were analyzed for inclusion. Renal status was determined by the provider with the presence of acute kidney injury (exclusion criteria) determined by the RIFLE criteria. Doses of patiromer and SPS were categorized as low dose or high dose. Low dose was defined a 8.4 g of patiromer or 15 g of SPS. High dose was defined as 16.8 g of patiromer and 30 g of SPS.
Duration	Data collection period: May 1, 2017 to March 31, 2019 Duration: within 24 hours
Outcome Measures	Primary: average potassium reduction at the time to recheck potassium values in all groups, low dose group, and high dose group
Baseline Characteristics		Patiromer (n= 49)	SPS (n= 50)	p-Value
	Age, years (SD)	60 (13.5)	62 (14.8)	0.58
	Male	21 (43%)	27 (54%)	0.75
	Body mass index (SD)	29.9% (8.5)	28.9% (7.1)	0.52
	Comorbidities Diabetes mellitus Congestive heart failure Cirrhosis	28 (57%) 9 (18%) 2 (4%)	29 (58%) 16 (32%) 3 (6%)	0.93 0.12 1.00
	Serum measurements Pre-dose K, mg/dL Pre-dose serum creatining (Scr), mg/dL Pre-dose Ca, mg/dL	5.6 2.6 8.5	5.7 2.07 8.6	0.08 0.11 0.21
	Renal status Normal CKD ESRD Transplant	11 (22%) 16 (33%) 15 (31%) 7 (14%)	14 (28%) 21 (42%) 9 (18%) 6 (12%)	0.46
	Diet Regular Low K/CKD Tube feeds Nephro	22 (45%) 22 (45%) 4 (8%) 1 (2%)	37 (74%) 11 (22%) 0 2 (4%)	<0.05
	Emergency department	0	10 (20%)	<0.05
	Time to recheck potassium levels, hours	11.9 (5.0)	14.6 (4.9)
Results	Endpoint	Patiromer (n= 49)	SPS (n= 50)	Difference (95% Confidence interval [CI])	p-Value
	Average potassium reduction in all groups, mEq/L (SD)	0.32 (0.65)	0.76 (0.63)	0.44 (0.18 to 0.69)	0.001
	Average potassium reduction in high-dose groups, mEq/L (SD)	n= 18 0.43 (0.62)	n= 31 0.84 (0.71)	0.40 (0 to 0.81)	0.052
	Average potassium reduction in low-dose group, mEq/L (SD)	n= 31 0.26 (0.67)	n= 19 0.64 (0.47)	0.26 (0.01 to 0.51)	0.038
Adverse Events	N/A
Study Author Conclusions	This study suggests a clinically significant reduction in potassium with SPS compared to patiromer. Although SPS was successful in demonstrating this outcome, due to well-documented adverse reactions in the literature and a time to onset of 6 hours, it cannot be recommended for use in acute hyperkalemia either.
InpharmD Researcher Critique	Baseline potassium levels averaged as 5.6 and 5.7 mEq/L in the patiromer and SPS groups, which may be considered as mild hyperkalemia. Therefore, treatment effect on those with moderate or severe hyperkalemia warrants further investigation. Twenty percent of patients in the SPS group presented in the emergency department versus zero in the patiromer group which could have influenced other factors such as the standard and quality of care the SPS group received. Safety data could not be retrieved and presents a major concern not answered by this study.

References:

Nguyen PT, Kataria VK, Sam TR, Hooper K, Mehta AN. Comparison of patiromer to sodium polystyrene sulfonate in acute hyperkalemia. Hosp Pharm. Published online August 5, 2021:00185787211037552.