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. [1-3]

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]

References:

[1] Liu M, Rafique Z. Acute management of hyperkalemia. Curr Heart Fail Rep. 2019;16(3):67-74. doi:10.1007/s11897-019-00425-2.
[2] Clinical Review Report: Sodium Zirconium Cyclosilicate (Lokelma): (AstraZeneca Canada Inc.): Indication: For the treatment of hyperkalemia in adults [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2020 May. Available from: https://www.ncbi.nlm.nih.gov/books/NBK563711/
[3] Palmer BF, Carrero JJ, Clegg DJ, et al. Clinical management of hyperkalemia. Mayo Clin Proc. 2021;96(3):744-762. doi:10.1016/j.mayocp.2020.06.014.
[4] Meaney CJ, Beccari MV, Yang Y, et al. Systematic review and meta-analysis of patiromer and sodium zirconium cyclosilicate: a new armamentarium for the treatment of hyperkalemia. Pharmacotherapy. 2017;37(4):401-411. doi:10.1002/phar.1906.

Literature Review

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

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?

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.