Patiromer in Patients with Kidney Disease and Hyperkalemia Receiving RAAS Inhibitors

Weir, Matthew R.; Bakris, George L.; Bushinsky, David A.; Mayo, Martha; Garza, Dahlia; Stasiv, Yuri; Wittes, Janet; Christ‐Schmidt, Heidi; Berman, Lance; Pitt, Bertram

doi:10.1056/nejmoa1410853

Cited by 536 publications

(572 citation statements)

References 28 publications

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“…The persistence of the mortality risk after hyperkalemic episode in our study calls for evolution of risk stratification strategies for hyperkalemia on the longer term, need for future studies to evaluate the mortality benefits of new hyperkalemia therapies [6] so as to evolve strategies that benefit higher risk mortality patients. Our study is a vital step in the identification of high risk mortality patients and evaluate the longer term mortality implications of hyperkalemia.…”

Section: Discussionmentioning

confidence: 88%

“…Furthermore, the predictors for long term mortality in survivors from index hyperkalemia have not been studied. Identification of these predictors will help to target high risk mortality groups with novel therapeutic agents [5,6].…”

Section: Discussionmentioning

confidence: 99%

“…Patiromer also showed a longer term decrease in serum potassium levels in 4 weeks and reduction in recurrence of hyperkalemia over subsequent 8 weeks [6]. It is notable that both studies did not include mortality end points.…”

Section: Introductionmentioning

confidence: 90%

“…of hyperkalemia is vital for evolution of utilization strategies for new drugs; especially patriromer which showed longer term decrease in potassium levels over 12 weeks [6]. The paucity of existing data on long term mortality in hyperkalemia precludes the accurate future assessment of mortality benefits of these new drugs.…”

Section: Archives Of Medicine Issn 1989-5216mentioning

confidence: 99%

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Long-term Mortality Outcomes of Hyperkalemic Patients in the Emergency Department Setting: A Case Control Study

Velagapudi¹,

O’Horo²,

Glinskii³

et al. 2017

Arch Med

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Background: The impact of an episode of hyperkalemia on long term mortality is not well studied. Such a study is vital for development of a utilization strategy for new drugs for the treatment of hyperkalemia. To study the long term impact of hyperkalemia on mortality, we conducted a retrospective, observational casecontrol study in a tertiary care emergency department. We compared cases of non-hemolyzed serum potassium >5.3 mEq/L with normokalemic controls. Allcause mortality and causes of death were determined from social security death index, national death index, and medical record review over a follow-up period of 490 patient years. Methods and Findings:A total of 287 consecutive subjects (223 cases, 64 controls) were identified among 14,483 patients. Cox proportional hazard regression showed that for each 1 mEq/L increase in admit potassium, all-cause mortality Hazard Ratio was 1.54, 95% Confidence Interval: 1.22-1.96. Subgroup analyses showed higher mortality in acute kidney injury and heart failure patients. Conclusion:Hyperkalemia predicted all-cause mortality, when adjusted for age, sex, Charlson comorbidity index, and significant covariates (heart failure and end stage renal disease). The deleterious effect of admit hyperkalemia persisted in survivors from index episode throughout the study period. Cardiovascular mortality was statistically more prevalent. Future studies are needed for risk stratification strategies and mortality impact of newer drugs.

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Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 90%

Section: Archives Of Medicine Issn 1989-5216mentioning

confidence: 99%

See 2 more Smart Citations

Long-term Mortality Outcomes of Hyperkalemic Patients in the Emergency Department Setting: A Case Control Study

Velagapudi¹,

O’Horo²,

Glinskii³

et al. 2017

Arch Med

View full text Add to dashboard Cite

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“…It is approved for the treatment of hyperkalaemia in the USA and in Europe 10, 11, 12. Patiromer has been shown to reduce serum K + in hyperkalaemic patients with CKD with or without other co‐morbidities, such as HF, diabetes mellitus, and/or hypertension 13, 14, 15. Patiromer has also been demonstrated in a randomized, double‐blind, placebo‐controlled study to prevent hyperkalaemia in normokalaemic patients with HF with or without CKD who were initiated on spironolactone 16.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of an individualized dose titration regimen of patiromer to prevent hyperkalaemia in patients with heart failure and chronic kidney disease

et al. 2018

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AimsHyperkalaemia risk precludes optimal renin–angiotensin–aldosterone system inhibitor use in patients with heart failure (HF), particularly those with chronic kidney disease (CKD). Patiromer is a sodium‐free, non‐absorbed potassium (K+)‐binding polymer approved for the treatment of hyperkalaemia. In PEARL‐HF, patiromer 25.2 g (fixed dose) prevented hyperkalaemia in HF patients with or without CKD initiating spironolactone. The current study evaluated the effectiveness of a lower starting dose of patiromer (16.4 g/day) followed by individualized titration in preventing hyperkalaemia and hypokalaemia when initiating spironolactone.Methods and resultsThis open‐label 8‐week study enrolled 63 patients with CKD, serum K+ 4.3–5.1 mEq/L, and chronic HF, who, based on investigator opinion, should receive spironolactone. Eligible patients started spironolactone 25 mg/day and patiromer 16.8 g/day (divided into two doses), with patiromer titrated to maintain serum K+ 4.0–5.1 mEq/L. Mean (standard deviation) serum K+ was 4.78 (0.51) mEq/L at baseline; weekly values were 4.48–4.70 mEq/L during treatment. Serum K+ of 3.5–5.5 mEq/L at the end of study treatment (primary endpoint) was achieved by 57 (90.5%) patients; 53 (84.1%) had serum K+ 4.0–5.1 mEq/L. One patient (1.6%) developed hypokalaemia, and two patients (3.2%) developed hypomagnesaemia. Spironolactone was increased to 50 mg/day in all patients; 43 (68%) patients required one or more patiromer dose titration. Adverse events (AEs) occurred in 36 (57.1%) patients, with a low rate of discontinuations [four (6.3%) patients]. The most common AE was mild to moderate abdominal discomfort [four (6.3%) patients].ConclusionsIn this open‐label study, patiromer 16.8 g/day followed by individualized titration maintained serum K+ within the target range in the majority of patients with HF and CKD, all of whom were uptitrated to spironolactone 50 mg/day, patiromer was well tolerated, with a low incidence of hyperkalaemia, hypokalaemia, and hypomagnesaemia.

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Effect of Patiromer on Serum Potassium Level in Patients With Hyperkalemia and Diabetic Kidney Disease

Bakris

Pitt

Weir

et al. 2015

JAMA

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387

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IMPORTANCE Hyperkalemia is a potentially life-threatening condition predominantly seen in patients treated with renin-angiotensin-aldosterone system (RAAS) inhibitors with stage 3 or greater chronic kidney disease (CKD) who may also have diabetes, heart failure, or both. OBJECTIVES To select starting doses for a phase 3 study and to evaluate the long-term safety and efficacy of a potassium-binding polymer, patiromer, in outpatients with hyperkalemia. DESIGN, SETTING, AND PARTICIPANTS Phase 2, multicenter, open-label, dose-ranging, randomized clinical trial (AMETHYST-DN), conducted at 48 sites in Europe from June 2011 to June 2013 evaluating patiromer in 306 outpatients with type 2 diabetes (estimated glomerular filtration rate, 15 to <60 mL/min/1.73 m 2 and serum potassium level >5.0 mEq/L). All patients received RAAS inhibitors prior to and during study treatment. INTERVENTIONS Patients were stratified by baseline serum potassium level into mild or moderate hyperkalemia groups and received 1 of 3 randomized starting doses of patiromer (4.2 g [n = 74], 8.4 g [n = 74], or 12.6 g [n = 74] twice daily [mild hyperkalemia] or 8.4 g [n = 26], 12.6 g [n = 28], or 16.8 g [n = 30] twice daily [moderate hyperkalemia]). Patiromer was titrated to achieve and maintain serum potassium level 5.0 mEq/L or lower. MAIN OUTCOMES AND MEASURES The primary efficacy end point was mean change in serum potassium level from baseline to week 4 or prior to initiation of dose titration. The primary safety end point was adverse events through 52 weeks. Secondary efficacy end points included mean change in serum potassium level through 52 weeks. RESULTS A total of 306 patients were randomized. The least squares mean reduction from baseline in serum potassium level at week 4 or time of first dose titration in patients with mild hyperkalemia was 0.35 (95% CI, 0.22-0.48) mEq/L for the 4.2 g twice daily starting-dose group, 0.51 (95% CI, 0.38-0.64) mEq/L for the 8.4 g twice daily starting-dose group, and 0.55 (95% CI, 0.42-0.68) mEq/L for the 12.6 g twice daily starting-dose group. In those with moderate hyperkalemia, the reduction was 0.87 (95% CI, 0.60-1.14) mEq/L for the 8.4 g twice daily starting-dose group, 0.97 (95% CI, 0.70-1.23) mEq/L for the 12.6 g twice daily starting-dose group, and 0.92 (95% CI, 0.67-1.17) mEq/L for the 16.8 g twice daily starting-dose group (P < .001 for all changes vs baseline by hyperkalemia starting-dose groups within strata). From week 4 through week 52, statistically significant mean decreases in serum potassium levels were observed at each monthly point in patients with mild and moderate hyperkalemia. Over the 52 weeks, hypomagnesemia (7.2%) was the most common treatment-related adverse event, mild to moderate constipation (6.3%) was the most common gastrointestinal adverse event, and hypokalemia (<3.5 mEq/L) occurred in 5.6% of patients. CONCLUSIONS AND RELEVANCE Among patients with hyperkalemia and diabetic kidney disease, patiromer starting doses of 4.2 to 16.8 g twice daily resulted in statistically signific...

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Patiromer in Patients with Kidney Disease and Hyperkalemia Receiving RAAS Inhibitors

Cited by 536 publications

References 28 publications

Long-term Mortality Outcomes of Hyperkalemic Patients in the Emergency Department Setting: A Case Control Study

Long-term Mortality Outcomes of Hyperkalemic Patients in the Emergency Department Setting: A Case Control Study

Evaluation of an individualized dose titration regimen of patiromer to prevent hyperkalaemia in patients with heart failure and chronic kidney disease

Effect of Patiromer on Serum Potassium Level in Patients With Hyperkalemia and Diabetic Kidney Disease

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