Efficacy Of Patiromer Research Articles

Efficacy of Patiromer in Management of Long-Weekend Hyperkalemia in Patients on Intermittent Hemodialysis: A Tertiary Centre Experience from Saudi Arabia

Efficacy of Patiromer in Management of Long-Weekend Hyperkalemia in Patients on Intermittent Hemodialysis: A Tertiary Centre Experience from Saudi Arabia

Real-world management of chronic and postprandial hyperkalemia in CKD patients treated with patiromer: a single-center retrospective study.

Hyperkalemia, one of the most important electrolyte abnormalities of chronic kidney disease (CKD), often limits the use of renin-angiotensin-aldosterone system inhibitors and can increase in the postprandial period. In this study we report a real-world experience with the new non-adsorbed potassium binder patiromer in stage 3b-4 CKD patients. Moreover, we performed a cross-sectional analysis to evaluate, for the first time, the efficacy of patiromer in the control of postprandial potassium concentrations. We retrospectively collected data of 40 patients at the time of patiromer initiation (T0), and after 2 (T2), 6 (T6) and 12 (T12) months of treatment. For cross sectional analysis, a blood sample was collected 2h after the main meal for the evaluation of postprandial potassium concentrations. Eighty-two point five percent of patients (33/40) reached normal potassium concentrations at T2. Serum potassium significantly decreased at T2 compared to T0 (5.13 ± 0.48 vs 5.77 ± 0.41mmol/L, respectively; p < 0.001) and the reduction remained significant during the follow-up (5.06 ± 0.36 at T6 and 5.77 ± 0.41 at T12; p < 0.001 vs T0). Renin-angiotensin-aldosterone system inhibitors were continued by 93% of patients (27/29). Adverse events were reported in 27.5% of patients and were all mild-to-moderate. Postprandial potassium concentrations did not significantly change compared to fasting state potassium measured at T12 (4.53 ± 0.33 vs 5.06 ± 0.36mmol/L; p = 0.15). In a real-world setting of advanced CKD patients, patiromer is a useful treatment for hyperkalemia, since it significantly reduces serum potassium levels over the long term and is able to maintain potassium concentrations in the normal range even in the post-prandial period.

Safety and Efficacy of Patiromer in Hyperkalemic Patients with CKD: A Pooled Analysis of Three Randomized Trials.

Hyperkalemia is a common electrolyte abnormality in patients with CKD, which is associated with worse outcomes and limits use of renin-angiotensin-aldosterone system inhibitors (RAASi). This post hoc subgroup analysis of three clinical trials evaluated the efficacy and safety of the sodium-free, potassium-binding polymer, patiromer, for the treatment of hyperkalemia in adults with nondialysis CKD. Data from the 4-week treatment periods of AMETHYST-DN, OPAL-HK, and TOURMALINE studies were combined. Patients had baseline diagnosis of CKD, hyperkalemia (serum potassium >5.0 mEq/L), and received patiromer 8.4-33.6 g/day. Patients were stratified by baseline eGFR into two subgroups: severe/end-stage CKD (stage 3b-5; eGFR <45 ml/min per 1.73 m2) and mild/moderate CKD (stage 1-3a; eGFR ≥45 ml/min per 1.73 m2). Efficacy was assessed by the change in serum potassium (mean±SE) from baseline to week 4. Safety assessments included incidence and severity of adverse events (AEs). Efficacy analyses (n=626; 62% male, mean age 66 years) included 417 (67%) patients with severe/end-stage CKD and 209 (33%) with mild/moderate CKD. Most patients were receiving RAASi therapy at baseline (severe/end-stage CKD 92%; mild/moderate CKD 98%). The mean±SE change in serum potassium (baseline to week 4) was -0.84±0.03 in the severe/end-stage CKD subgroup, and -0.60±0.04 mEq/L in the mild/moderate CKD subgroup. AEs were reported for 40% and 27% patients in the severe/end-stage and mild/moderate CKD subgroups, respectively, with 16% and 12% reporting AEs considered related to patiromer. The most frequent AEs were mild-to-moderate constipation (8% and 3%) and diarrhea (4% and 2%). AEs leading to patiromer discontinuation occurred in 6% and 2% of patients with severe/end-stage CKD, and mild/moderate CKD, respectively. Patiromer was effective for treatment of hyperkalemia and well tolerated in patients across stages of CKD, most of whom were receiving guideline-recommended RAASi therapy.

Safety and Efficacy of Patiromer in Kidney and Liver Transplant Recipients

Kidney transplant recipients (KTR) and liver transplant recipients (LTR) are at risk for elevation in serum potassium post-transplant. Patiromer is approved by the Food and Drug Administration for the treatment of hyperkalemia, but there is limited safety and efficacy data for its use in solid organ transplantation.

Efficacy of Patiromer and Sodium Polystyrene Sulfonate on Potassium Levels in Chronic Hemodialysis Patients

Efficacy of Patiromer and Sodium Polystyrene Sulfonate on Potassium Levels in Chronic Hemodialysis Patients

FC 024SAFETY AND EFFICACY OF PATIROMER FOR HYPERKALAEMIA IN PATIENTS WITH STAGE 1-3A OR STAGE 3B-5 CHRONIC KIDNEY DISEASE: POOLED ANALYSIS OF THE AMETHYST-DN, OPAL-HK AND TOURMALINE TRIALS

Abstract Background and Aims In patients with CKD and/or heart failure (HF), hyperkalaemia (HK) is a major problem which limits the use of guideline-recommended renin–angiotensin–aldosterone inhibitors (RAASi). Dose reduction or cessation of RAASi therapy results in increased morbidity and mortality. Improved strategies to mitigate HK are required to improve clinical outcomes. Patiromer is a non-absorbed, sodium-free, K+ binder that has been shown to reduce serum K+ in patients with HK, and thereby enable RAASi therapy. We conducted a post-hoc analysis to evaluate patiromer’s efficacy and safety in two HK subgroups by CKD severity: patients with Stage 3b-5 CKD and those with Stage 1-3a. Method Data were combined from the initial 4 weeks of treatment of three studies (AMETHYST-DN, OPAL-HK and TOURMALINE). Eligible patients had a diagnosis of CKD and HK (local laboratory serum K+ &amp;gt;5.0 mmol/L) and received patiromer 8.4 to 33.6 g/day to start. Subgroups were identified by baseline estimated glomerular filtration rate (eGFR): stage 3b–5 (severe/end-stage CKD) and stage 1–3a (mild/moderate CKD). The efficacy population comprised randomised patients who received ≥1 dose patiromer and had ≥1 post-baseline serum K+ assessment available. Efficacy was evaluated as the mean (± standard error [SE]) change in central laboratory serum K+ from baseline to Week 4 (primary endpoint in AMETHYST-DN and OPAL-HK; secondary endpoint in TOURMALINE). Safety outcomes, including incidence and severity of adverse events (AEs) with onset during the 4-week evaluation period, were assessed in all randomised patients who received ≥1 dose of patiromer. Results Of the 626 patients evaluable for efficacy, 61.8% were male, mean±standard deviation (SD) age was 65.6±9.8 years and 417 (66.6%) had stage 3b-5 CKD, including 27 (6.5%) patients with stage 5 CKD. Approximately 34% of patients in both subgroups had HF, predominantly NYHA Class II. Baseline characteristics were similar between the stage 3b–5 and stage 1–3a CKD subgroups, except for serum K+ (mean±SD: 5.47±0.41 and 5.32±0.42 mmol/L, respectively), eGFR (mean±SD: 27.9±9.0 and 58.0±12.8 mL/min/1.73m2), and spot urine albumin:creatinine ratio (mean±SD: 1263±1921 and 606±1241 mg/g). In total, 91.8% of patients with stage 3b-5 CKD and 97.6% of patients with stage 1-3a CKD were receiving RAASi therapy at baseline. Patiromer induced early reductions in serum K+, with mean levels decreasing from baseline to below 5.0 mmol/L by Day 3 or Week 1 in the stage 3b–5 and stage 1–3a CKD subgroups, respectively (Figure). The mean change in serum K+ from baseline to Week 4 was −0.84±0.03 and −0.60±0.04 mmol/L in patients with stage 3b–5 and stage 1–3a CKD, respectively. Overall, 96.4% and 99.0% of patients with stage 3b–5 and stage 1–3a CKD, respectively, achieved normokalaemia (≥1 serum K+ value 3.8–5.0 mEq/L) during the 4 weeks of treatment. In total, 421 patients with CKD stage 3b–5 and 211 with CKD stage 1–3a were evaluable for safety. AEs were reported by 168 (39.9%) and 58 (27.5%) patients with stage 3b–5 and stage 1–3a CKD, respectively. The most frequent AEs in stage 3b–5 and stage 1–3a CKD patients, respectively, were constipation (7.8% and 2.8%) and diarrhoea (4.0% and 1.9%); all cases were mild or moderate in severity. AEs leading to patiromer discontinuation occurred in 5.7% and 2.4% of stage 3b–5 CKD and stage 1–3a CKD patients, respectively. Conclusion This pooled analysis of three clinical trials clearly demonstrated the efficacy of patiromer to effectively treat HK in patients with CKD, regardless of early or advanced disease, the majority of whom were receiving guideline-recommended RAASi blockade. Patiromer was well tolerated with mild gastrointestinal events in a small percentage of patients, and very few discontinuations. Patiromer is an appropriate choice for the control of HK in patients with CKD stage 3b–5.

Patiromer and Spironolactone in Resistant Hypertension and Advanced CKD: Analysis of the Randomized AMBER Trial.

Mineralocorticoid receptor antagonists reduce mortality in patients with heart failure with reduced ejection fraction and have become a standard of care in those with resistant hypertension (rHTN). Yet, their use is limited among patients with CKD, primarily due to hyperkalemia. AMBER was a multicenter, randomized, double-blind, placebo-controlled, parallel-group study that reported that the use of the potassium-binding drug patiromer allowed a more persistent use of spironolactone in patients with CKD and rHTN. In this report, we compare the safety and efficacy of patiromer in advanced CKD as a prespecified analysis. Of the 295 patients randomized, 66 fell into the eGFR 25 to <30 subgroup. In this subgroup, persistent use of spironolactone was seen in 19 of 34 (56%) in the placebo group and 27 of 32 (84%) in the patiromer group (absolute difference 29%; P<0.02). In the eGFR 30-45 subgroup, persistent use of spironolactone was seen in 79 of 114 (69%) in the placebo group and 99 of 115 (86%) in the patiromer group (absolute difference 17%; P=0.003). There was no significant interaction between eGFR subgroups (P=0.46). Systolic BP reduction with spironolactone in the eGFR 25 to <30 subgroup was 6-7 mm Hg; in the eGFR 30-45 subgroup, it was 12-13 mm Hg. There was no significant interaction between eGFR subgroups on BP reduction (P=0.79). Similar proportions of patients reported adverse events (59% in the eGFR 25 to <30 subgroup; 53% in the eGFR 30-45 subgroup). Patiromer facilitates the use of spironolactone among patients with rHTN, and its efficacy and safety are comparable in those with eGFR 25 to <30 and 30-45 ml/min per 1.73 m2. Clinicaltrials.gov, NCT03071263.

Largest Experience of Safety and Efficacy of Patiromer in Solid Organ Transplant.

Supplemental Digital Content is available in the text.

P0187COMPARING OPAL-HK DATA TO REAL-WORLD DATA FROM THE UNITED KINGDOM: HOW EFFECTIVE IS PATIROMER AT ACHIEVING NORMOKALAEMIA?

Abstract Background and Aims The first phase of the published OPAL-HK study showed that Patiromer, an oral potassium binder, was effective at reducing serum potassium levels in patients with chronic kidney disease (CKD) stages 3 to 4. This phase was a 4-week, single-group treatment phase. Given the lack of a control arm, the aim of our study was to use real-world data from a large CKD cohort to provide a control comparison to evaluate the efficacy of Patiromer in normalising serum potassium. Method The initial phase of OPAL-HK comprised 243 patients with CKD G3-4 with a baseline serum potassium of 5.1 to &amp;lt;6.5mmol/L. To acquire a comparative matched cohort, patients were selected from the Salford Kidney Study (SKS), a prospective observational cohort study in the United Kingdom that has been recruiting patients aged ≥18 years old with CKD G3-5 since 2002. A 3-step process was applied to generate a propensity matched cohort. First, patients were chosen if they had an outpatient potassium level at any point after recruitment into SKS between 5.1mmol/L to &amp;lt;6.5mmol/L and whose next outpatient potassium level was checked 24 to 42 days (3.5 to 6 weeks) later (n=755). Second, all key OPAL-HK inclusion and exclusion criteria were applied. This left 162 patients who were then accurately matched in a 1:1 fashion to the 243 OPAL-HK patients using propensity score matching based on 6 baseline variables: age, gender, eGFR, diabetes mellitus, heart failure and potassium level. This produced a cohort of 87 SKS patients matched to their 87 OPAL-HK partner patients. We compared the two patient groups for the following OPAL-HK study endpoints: the mean change in serum potassium from baseline to follow-up at week 4, and the proportion of patients with a serum potassium of 3.8 to &amp;lt;5.1mmol/L at week 4. Results The groups were extremely well matched: between SKS vs. OPAL-HK, the mean (±SD) age was 63.9±13.3 vs. 63.7±9.5years (p=0.93); mean eGFR was 30.9±11.6 vs. 31.2±11.7ml/min/1.73m2 (p=0.85); 45 vs. 46 patients were diabetics (p=0.88); 29 vs. 24 had heart failure (p=0.41) and the mean potassium was 5.5±0.3mmol/L in both groups (p=0.68). The follow-up in the SKS cohort was 31±5 days. At the end of follow-up, the mean potassium level remained 5.5±0.3mmol/L in SKS patients but had reduced to 4.5±0.5mmol/L in the OPAL-HK group (p&amp;lt;0.001), a mean (±SE) change of -1.00±0.06mmol/L. For the secondary endpoint, 74% of patients in OPAL-HK reached the target potassium range of 3.8 to &amp;lt;5.1mmol/L at week 4 compared with 0% from the comparator SKS cohort (see Figure). Conclusion Using real-world data as a tightly-matched control arm for the first phase of the OPAL-HK study, Patiromer is shown to be effective at reducing potassium levels in patients with CKD G3-4.

1-year safety and efficacy of patiromer for hyperkalemia in heart failure patients with chronic kidney disease on renin-angiotensin-aldosterone system inhibitors

1-year safety and efficacy of patiromer for hyperkalemia in heart failure patients with chronic kidney disease on renin-angiotensin-aldosterone system inhibitors

Patiromer in Patients with Kidney Disease and Hyperkalemia Receiving RAAS Inhibitors

BackgroundHyperkalemia increases the risk of death and limits the use of inhibitors of the renin–angiotensin–aldosterone system (RAAS) in high-risk patients. We assessed the safety and efficacy of patiromer, a nonabsorbed potassium binder, in a multicenter, prospective trial.MethodsPatients with chronic kidney disease who were receiving RAAS inhibitors and who had serum potassium levels of 5.1 to less than 6.5 mmol per liter received patiromer (at an initial dose of 4.2 g or 8.4 g twice a day) for 4 weeks (initial treatment phase); the primary efficacy end point was the mean change in the serum potassium level from baseline to week 4. Eligible patients at the end of week 4 (those with a baseline potassium level of 5.5 to <6.5 mmol per liter in whom the level decreased to 3.8 to <5.1 mmol per liter) entered an 8-week randomized withdrawal phase in which they were randomly assigned to continue patiromer or switch to placebo; the primary efficacy end point was the between-group difference in the median change in the serum potassium level over the first 4 weeks of that phase.ResultsIn the initial treatment phase, among 237 patients receiving patiromer who had at least one potassium measurement at a scheduled visit after day 3, the mean (±SE) change in the serum potassium level was −1.01±0.03 mmol per liter (P<0.001). At week 4, 76% (95% confidence interval, 70 to 81) of the patients had reached the target potassium level (3.8 to <5.1 mmol per liter). Subsequently, 107 patients were randomly assigned to patiromer (55 patients) or placebo (52 patients) for the randomized withdrawal phase. The median increase in the potassium level from baseline of that phase was greater with placebo than with patiromer (P<0.001); a recurrence of hyperkalemia (potassium level, ≥5.5 mmol per liter) occurred in 60% of the patients in the placebo group as compared with 15% in the patiromer group through week 8 (P<0.001). Mild-to-moderate constipation was the most common adverse event (in 11% of the patients); hypokalemia occurred in 3%.ConclusionsIn patients with chronic kidney disease who were receiving RAAS inhibitors and who had hyperkalemia, patiromer treatment was associated with a decrease in serum potassium levels and, as compared with placebo, a reduction in the recurrence of hyperkalemia. (Funded by Relypsa; OPAL-HK ClinicalTrials.gov number, NCT01810939.)