Real or Perceived: Hyperkalemia Is a Major Deterrent for Renin-Angiotensin Aldosterone System Inhibition in Heart Failure

McCullough, Peter A.; Rangaswami, Janani

doi:10.1159/000485645

Cited by 10 publications

(13 citation statements)

References 14 publications

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“…Potassium (K + ) homeostasis can be compromised among individuals with CKD, heart failure (HF), and diabetes mellitus and in those using renin-angiotensin-aldosterone system inhibitors (RAASis). Consequently, these individuals are at greater risk of persistent or recurrent hyperkalemia, and discontinuation of beneficial medications, such as RAASis, may be recommended (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11). Despite potentially dangerous sequelae of hyperkalemia, no standard outpatient treatment paradigm exists (12).…”

Section: Introductionmentioning

confidence: 99%

Sodium Zirconium Cyclosilicate among Individuals with Hyperkalemia

Spinowitz

Fishbane

Pèrgola

et al. 2019

CJASN

142

135

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Background and objectives Oral sodium zirconium cyclosilicate (formerly ZS-9) binds and removes potassium via the gastrointestinal tract. Sodium zirconium cyclosilicate-associated restoration and maintenance of normokalemia and adverse events were evaluated in a two-part, open label, phase 3 trial. Design, setting, participants, & measurements In the correction phase, adult outpatients with plasma potassium $5.1 mmol/L (i-STAT Point-of-Care) received sodium zirconium cyclosilicate 10 g three times daily for 24-72 hours until normokalemic (potassium =3.5-5.0 mmol/L). Qualifying participants entered the #12-month maintenance phase and received sodium zirconium cyclosilicate 5 g once daily titrated to maintain normokalemia without dietary or medication restrictions. Prespecified primary end points were restoration of normal serum potassium values (3.5-5.0 mmol/L) during the correction phase and maintenance of serum potassium #5.1 mmol/L during the maintenance phase. Adverse events were assessed throughout. Results Of 751 participants, 746 (99%) achieved normokalemia during the correction phase (mean serum potassium =4.8 mmol/L; 95% confidence interval, 4.7 to 4.8) and entered the maintenance phase; 466 (63%) participants completed the 12-month trial. Participants were predominantly white, men, and age $65 years old; 74% had an eGFR,60 ml/min per 1.73 m 2 , and 65% used renin-angiotensin-aldosterone system inhibitors. Mean time on sodium zirconium cyclosilicate was 286 days. Mean daily sodium zirconium cyclosilicate dose was 7.2 g (SD=2.6). Over months 3-12, mean serum potassium was 4.7 mmol/L (95% confidence interval, 4.6 to 4.7); mean serum potassium values #5.1 and #5.5 mmol/L were achieved by 88% and 99% of participants, respectively. Of 483 renin-angiotensin-aldosterone system inhibitor users at baseline, 87% continued or had their dose increased; 11% discontinued. Among 263 renin-angiotensin-aldosterone system inhibitor-naïve participants, 14% initiated renin-angiotensin-aldosterone system inhibitor therapy. Overall, 489 (66%) participants experienced adverse events during the maintenance phase, and 22% experienced a serious adverse event. Of eight (1%) deaths, none were considered related to sodium zirconium cyclosilicate. Nine (1%) and 34 (5%) participants experienced serum potassium ,3.0 and 3.0-3.4 mmol/L, respectively. Conclusions After achieving normokalemia, individualized once daily sodium zirconium cyclosilicate was associated with maintenance of normokalemia without substantial renin-angiotensin-aldosterone system inhibitor changes for #12 months.

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Section: Introductionmentioning

confidence: 99%

Sodium Zirconium Cyclosilicate among Individuals with Hyperkalemia

Spinowitz

Fishbane

Pèrgola

et al. 2019

CJASN

142

135

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“…As a consequence, hyperkalaemia is generally a deterrent for the use of these potentially life‐saving therapies, determining, in addition to the negative role of hyperkalaemia itself, an unfavourable impact on patients with CKD, HF or diabetes. 21 , 22 , 23 Large observational studies have demonstrated an association between hyperkalaemia and an increased risk of death. 21 , 24 , 25 , 26 Until recently, there has been a dearth of drugs for the long‐term prevention of hyperkalaemia; urgent treatments, in addition to diuretics and dialysis, involve the administration of sodium polystyrene sulphonate, intravenous insulin‐glucose or sodium bicarbonate and nebulised beta‐agonists 17 that may be contraindicated in diabetic or HF patients.…”

Section: Discussionmentioning

confidence: 99%

Prevalence, clinical impact and costs of hyperkalaemia: Special focus on heart failure

Maggioni

Dondi²,

Andreotti

et al. 2021

Eur J Clin Investigation

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“…In treated patients, a high serum potassium could serve as a proxy for higher levels of sympathetic and renin–angiotensin system inhibition due to medical therapy, particularly MRA agents. In this scenario, more intensified therapy would be expected to result in lower rates of HF hospitalization and cardiovascular death despite the higher concentration of serum potassium 6 . In the present study, the investigators note that the addition of time‐varying potassium improved risk stratification for cardiovascular deaths, hospitalization for HF, and all‐cause death relative to other HF risk models.…”

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confidence: 99%