Patiromer: A Novel Potassium-Binding Polymer for Treatment of Hyperkalemia
What is the long-term safety and efficacy of a potassium-binding polymer, patiromer, in outpatients with hyperkalemia?
AMETHYST-DN was a phase 2, multicenter, open-label, dose-ranging, randomized clinical trial conducted at 48 sites in Europe, from June 2011 to June 2013. Eligible patients had type 2 diabetes and chronic kidney disease (estimated glomerular filtration rate, 15 to <60 ml/min/1.73 m2) with a serum potassium level >5.0 mEq/L. Study components included a run-in period of up to 4 weeks’ duration, an 8-week treatment phase, and a long-term maintenance phase of up to 44 weeks’ duration. All patients received renin-angiotensin-aldosterone system (RAAS) inhibitors prior to and during study treatment. Patients were stratified by baseline serum potassium level (stratum 1: >5.0-5.5 mEq/L [mild hyperkalemia]; stratum 2: >5.5-6.0 mEq/L [moderate hyperkalemia]). Then patients were randomly assigned in a 1:1:1 ratio to one of three patiromer starting doses per stratum (mild hyperkalemia: 8.4 g/day, 16.8 g/day, 25.2 g/day; moderate hyperkalemia: 16.8 g/day, 25.2 g/day; and 33.6 g/day). The primary efficacy endpoint was the mean change in serum potassium level from baseline to week 4 or prior to the initiation of dose titration. The primary safety endpoint was the frequency and severity of adverse events through the end of the maintenance phase at week 52.
A total of 306 patients were randomized. The least squares mean reduction from baseline in serum potassium level at week 4 or at the time of first dose titration in patients with mild hyperkalemia was 0.35 (95% confidence interval [CI], 0.22-0.48) mEq/L for the 8.4 g/day group, 0.51 (95% CI, 0.38-0.64) mEq/L for the 16.8 g/day group, and 0.55 (95% CI, 0.42-0.68) mEq/L for the 25.2 g/day group. In those with moderate hyperkalemia, the least squares mean reduction from baseline in serum potassium level at week 4 or at the time of first dose titration was 0.87 (95% CI, 0.60-1.14) mEq/L for the 16.8 g/day group, 0.97 (95% CI, 0.70-1.23) mEq/L for the 25.2 g/day group, and 0.92 (95% CI, 0.67-1.17) mEq/L for the 33.5 g/day group. These reductions were sustained through 52 weeks. Over 52 weeks, 20% of patients reported an adverse event considered by the investigator to be related to patiromer. Among treatment-related adverse events, the most frequently reported were hypomagnesemia (7.2%), constipation (4.6%), and diarrhea (2.7%). No adverse events of worsening chronic kidney disease were considered by the study investigators to be related to the study drug.
In patients with diabetic kidney disease and varying degrees of hyperkalemia, patiromer significantly reduced serum potassium levels across a range of doses (8.4-33.6 g/day).
This is an important study that helps establish the safety and efficacy of patiromer. Patiromer is a novel potassium-binding polymer that uses calcium rather than sodium as the counter ion exchange, as in sodium polystyrene sulfate (the only drug specifically indicated for the treatment of hyperkalemia in the United States). The sodium load in sodium polystyrene sulfate may contribute to fluid-retention; this agent is also limited by its questionable efficacy and gastrointestinal side effects. Patiromer may overcome these limitations and relieve the hyperkalemia that potentially restricts the use of RAAS inhibitors in those with diabetic kidney disease.
Keywords: Diabetes Mellitus, Type 2, Diabetic Nephropathies, Glomerular Filtration Rate, Heart Failure, Hyperkalemia, Kidney Diseases, Metabolic Syndrome X, Polymers, Potassium, Polystyrenes, Renin-Angiotensin System, Renal Insufficiency, Chronic
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