RESUMO
RATIONALE & OBJECTIVE: Older people are more likely to have reduced kidney function and multiple comorbid conditions predisposing them to hyperkalemia. This post hoc subgroup analysis aimed to evaluate the effectiveness of patiromer, a sodium-free nonabsorbed polymer, in lowering serum potassium levels in older patients receiving a renin-angiotensin-aldosterone system inhibitor with chronic kidney disease (CKD), type 2 diabetes mellitus (T2DM), and hypertension. STUDY DESIGN: Post hoc subgroup analysis of the randomized open-label AMETHYST-DN clinical trial. SETTING & PARTICIPANTS: Multicenter clinical trial. Individuals 75 years and older with CKD, T2DM, hypertension, and hyperkalemia at baseline (N = 60; mean age, 77 years; 30 men [50%]; mean estimated glomerular filtration rate, 41.6 ± 14.3 mL/min/1.73 m2). INTERVENTION: Patients with hyperkalemia were randomly assigned to receive patiromer at doses ranging from 4.2 to 16.8 g twice daily. OUTCOMES: We evaluated changesin serum potassium levels from baseline to week 4 and time points through 52 weeks. Long-term safety and tolerability were assessed through the end of 52 weeks and included frequency of adverse events, clinical laboratory measurements, and vital signs. RESULTS: Of 306 AMETHYST-DN participants, 60 were 75 years or older. All 60 patients had CKD and T2DM; 37% had heart failure. At screening, patients had an estimated glomerular filtration rate of 42 mL/min/1.73 m2, median urinary albumin-creatinine ratio of 127 mg/g, and baseline mean serum potassium level of 5.19 mEq/L. Mean serum potassium level was reduced at each time point from the first postbaseline visit (day 3) through week 52. LIMITATIONS: This small subgroup analysis was not prespecified and therefore randomization was lost; thus, it should be considered hypothesis generating. CONCLUSIONS: Among older patients with hyperkalemia and diabetic kidney disease, treatment with patiromer resulted in significant reductions in serum potassium levels after 4 weeks and lasted through 52 weeks. Patiromer was effective in lowering serum potassium levels and was well tolerated in older patients. FUNDING: Vifor Pharma, Inc. TRIAL REGISTRATION: NCT01371747.
RESUMO
BACKGROUND: Older people are predisposed to hyperkalemia because of impaired renal function, comorbid conditions, and polypharmacy. Renin-angiotensin-aldosterone system inhibitors (RAASi), which are recommended to treat chronic kidney disease and heart failure augment the risk. Patiromer, a nonabsorbed potassium binder, was shown in the phase 3 OPAL-HK study to decrease serum potassium in patients with chronic kidney disease taking RAASi. We studied the efficacy and safety of patiromer in a prespecified subgroup of patients aged ≥65 years from OPAL-HK. METHODS: Chronic kidney disease patients with mild or moderate-to-severe hyperkalemia received patiromer, initially 8.4 g/d or 16.8 g/d, respectively, for 4 weeks (treatment phase, part A). Eligible patients entered an 8-week randomized withdrawal phase (part B) and continued patiromer or switched to placebo. RESULTS: Mean ± standard error change in serum potassium from baseline to week 4 of part A (primary endpoint) in patients aged ≥65 years was -1.01 ± 0.05 mEq/L (P < .001); 97% achieved serum potassium 3.8-<5.1 mEq/L. The serum potassium increase during the first 4 weeks of part B was greater in patients taking placebo than in those taking patiromer (P < .001). Fewer patients taking patiromer (30%) than placebo (92%) developed recurrent hyperkalemia (serum potassium ≥5.1 mEq/L). Mild-to-moderate constipation occurred in 15% (part A) and 7% (part B) of patients aged ≥65 years. Serum potassium <3.5 mEq/L and serum magnesium <1.4 mg/dL were infrequent (4% each in patients aged ≥65 years in part A). CONCLUSIONS: Patiromer reduced recurrent hyperkalemia and was well tolerated in older chronic kidney disease patients taking RAASi.