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

ABSTRACT: AIMS:Hyperkalaemia 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 RESULTS:This 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]. CONCLUSIONS:In 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.

SUBMITTER: Pitt B

PROVIDER: S-EPMC5933966 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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

Pitt Bertram B Bushinsky David A DA Kitzman Dalane W DW Ruschitzka Frank F Metra Marco M Filippatos Gerasimos G Rossignol Patrick P Du Mond Charles C Garza Dahlia D Berman Lance L Lainscak Mitja M

ESC heart failure 20180125 3

<h4>Aims</h4>Hyperkalaemia 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<sup>+</sup> )-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 ...[more]

PMID: 29369537

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Project description:AimsHyperkalaemia (HK) is common in heart failure (HF) patients, related to renal dysfunction and medical treatment. It limits medical therapy optimization, which impacts prognosis. New potassium (K) binders help control HK, allowing better medical management of HF.Methods and resultsA retrospective multicentre register included all outpatients with HF and HK (K ≥ 5.1 mEq/L) treated with patiromer according to current recommendations. We evaluated analytic and clinical parameters before starting the treatment and at 7, 30 and 90 days, as well as adverse events related to patiromer and treatment optimization. We included 74 patients (71.6% male) with a mean age of 70.8 years (SD 9.2). Sixty-seven patients (90.5%) presented HK in the previous year. Forty patients (54.1%) underwent down-titration of a renin-angiotensin-aldosterone inhibitor (RAASi) or a mineralocorticoid receptor antagonist (MRA), and 27 (36.5%) stopped any of them due to HK. Initial K was 5.5 mEq/L (SD 0.6), with a significantly reduction at 7 days (4.9 mEq/L (SD 0.8); P < 0.001), maintained at 90 days (4.9 mEq/L (SD 0.8); P < 0.001). There were no other electrolyte disturbances, with a slight improvement in renal function [glomerular filtration rate 39.6 mL/min (SD 20.4) to 42.7 mL/min (SD 23.2); P = 0.005]. Adverse events were reported in 33.9% of patients, the most common being hypomagnesaemia (16.3%), gastrointestinal disturbances (14.9%) and HK (2.8%). Withdrawal of patiromer was uncommon (12.2%) due to gastrointestinal disturbances in 66.7% of cases. Nine patients (12.2%) started on a RAASi, and 15 patients (20.3%) on an MRA during the follow-up. Forty-five patients (60.8%) increased the dose of RAASi or MRA, increasing to target doses in 5.4 and 10.8% of patients, respectively. At 90 days, NTproBNP values were reduced from 2509.5 pg/mL [IQR 1311-4,249] to 1396.0 pg/mL [IQR 804-4263]; P = 0.003, but the reduction was only observed in those who optimized HF medical treatment [NTproBNP from 1950.5 pg/mL (IQR 1208-3403) to 1349.0 pg/mL (IQR 804-2609); P < 0.01]. NYHA functional class only improved in 7.5% of patients, corresponding with those who optimized HF medical treatment. Compared with the previous 3 months before patiromer treatment, the rate of hospitalization was reduced from 28.4 to 10.9% (P < 0.01), and the emergency room visits from 18.9 to 5.4% (P < 0.01).ConclusionsIn a real-life cohort of patients with HF, patiromer reduced and maintained K levels during 3 months of follow-up. The most common adverse events were hypomagnesaemia and gastrointestinal disturbances. Patiromer helps optimize medical treatment, increasing the percentage of patients treated with RAASi and MRA at target doses. At the end of follow-up, natriuretic peptides values and hospital visits were reduced, suggesting the benefit of optimizing HF medical treatment.

Project description:BackgroundChronic kidney disease (CKD) patients with and without heart failure (HF) often present with hyperkalaemia (HK) leading to increased risk of hospitalisations, cardiovascular related events and cardiovascular-related mortality. Renin-angiotensin-aldosterone system inhibitor (RAASi) therapy, the mainstay treatment in CKD management, provides significant cardiovascular and renal protection. Nevertheless, its use in the clinic is often suboptimal and treatment is frequently discontinued due to its association with HK. We evaluated the cost-effectiveness of patiromer, a treatment known to reduce potassium levels and increase cardiorenal protection in patients receiving RAASi, in the UK healthcare setting.MethodsA Markov cohort model was generated to assess the pharmacoeconomic impact of patiromer treatment in regulating HK in patients with advanced CKD with and without HF. The model was generated to predict the natural history of both CKD and HF and quantify the costs and clinical benefits associated with the use of patiromer for HK management from a healthcare payer's perspective in the UK.ResultsEconomic evaluation of patiromer use compared to standard of care (SoC) resulted in increased discounted life years (8.93 versus 8.67) and increased discounted quality-adjusted life years (QALYs) (6.36 versus 6.16). Furthermore, patiromer use resulted in incremental discounted cost of £2,973 per patient and an incremental cost-effectiveness ratio (ICER) of £14,816 per QALY gained. On average, patients remained on patiromer therapy for 7.7 months, and treatment associated with a decrease in overall clinical event incidence and delayed CKD progression. Compared to SoC, patiromer use resulted in 218 fewer HK events per 1,000 patients, when evaluating potassium levels at the 5.5-6 mmol/l; 165 fewer RAASi discontinuation episodes; and 64 fewer RAASi down-titration episodes. In the UK, patiromer treatment was predicted to have a 94.5% and 100% chance of cost-effectiveness at willingness-to-pay thresholds (WTP) of £20,000/QALY and £30,000/QALY, respectively.ConclusionThis study highlights the value of both HK normalisation and RAASi maintenance in CKD patients with and without HF. Results support the guidelines which recommend HK treatment, e.g., patiromer, as a strategy to enable the continuation of RAASi therapy and improve clinical outcomes in CKD patients with and without HF.

Project description:BackgroundHyperkalaemia is a potential life-threatening electrolyte abnormality. Although renin-angiotensin-aldosterone system inhibitors (RAASi) are potentially life-saving, they may contribute to hyperkalaemia.MethodsThe prevalence, comorbidities, comedications and 1-year outcomes of patients admitted or treated for hyperkalaemia were investigated in a large healthcare administrative database including 12 533 230 general population inhabitants. A similar analysis was performed in the Italian Network on Heart Failure (IN-HF), a cardiology registry of 1726 acute and 7589 chronic HF patients, stratified by serum potassium. General practice healthcare costs related to hyperkalaemia were also assessed. Hyperkalaemia was defined by hospital coding, potassium-binder prescription or serum levels (mild: 5-5.4, moderate-severe: ≥5.5 mmol/L).ResultsIn the general population, the prevalence of hyperkalaemia was 0.035%. After excluding patients on haemodialysis, hyperkalaemia in the community (n = 2314) was significantly and directly associated with diabetes, chronic kidney disease, HF, RAASi prescriptions, 1-year hospitalisations and threefold annual healthcare costs, compared to age- and sex-matched non-hyperkalaemic subjects (n = 2314). In the IN-HF registry, hyperkalaemia affected 4.3% of acute and 3.6% of chronic patients and was significantly associated with diabetes, kidney disease and lesser use of RAASi, compared to normokalaemic patients. Among patients hospitalised for acute HF, those with hyperkalaemia at entry had significantly higher 1-year all-cause mortality compared with normokalaemic patients, even after adjustment for available confounders.ConclusionsHyperkalaemia in the general population, although uncommon, was associated with increased hospitalisations and tripling of healthcare costs. Among HF patients, hyperkalaemia was common and associated with underuse of RAASi; in acutely decompensated patients, it remained independently associated with 1-year all-cause mortality.

Project description:BackgroundMale hypogonadism (testosterone level < 300 ng/dl) is a clinical syndrome that results from failure of the testis to produce physiological levels of testosterone. Most marketed testosterone replacement therapy products often require multiple dose adjustment clinic visits to achieve the desired, eugonadal testosterone levels.ObjectiveTo evaluate the efficacy and safety of a novel oral testosterone undecanoate therapy for the treatment of hypogonadism.Material and methodsNinety-five (N = 95) hypogonadal men were enrolled in this open-label, single-arm, multicenter study in the United States (NCT03242590). Subjects received 225 mg of oral testosterone undecanoate (TLANDO) twice a day for 24 days without dose adjustment. Primary efficacy was percentages of subjects who achieved mean 24-h testosterone levels within the eugonadal range and secondary efficacies were evaluated based on the upper limit of lab normal range of testosterone concentration.ResultsSubjects enrolled were on average age of 56 years, with about 17% of subjects older than 65 years. The mean body mass index was 32.8 kg/m2 . The baseline mean total testosterone values were below the normal range (202 ± 74 ng/dl). Post-treatment with 450 mg testosterone undecanoate daily dose without dose adjustment, 80% of subjects (95% confidence interval of 72%-88%) achieved a testosterone Cavg in the normal range and restored testosterone levels to mean testosterone Cavg of 476 ± 184 ng/dl at steady state. Testosterone restoration was comparable to other approved testosterone replacement therapy products. TLANDO was well tolerated with no deaths, no drug-related serious adverse events, and no hepatic adverse events.Discussion and conclusionsTLANDO restored testosterone levels to the normal range in the majority of hypogonadal males. This new oral testosterone replacement therapy can provide an option for no-titration oral testosterone replacement therapy. This therapy has the potential to improve patient compliance in testosterone replacement therapy.

Project description:Background and objectiveCertain patients with heart failure (HF) are unable to tolerate spironolactone therapy due to hyperkalemia. Patiromer is a novel agent used to treat hyperkalemia and has been shown to be efficacious, safe, and well-tolerated. The potential clinical outcomes and economic value of using patiromer and spironolactone in patients with HF unable to otherwise tolerate spironolactone due to hyperkalemia are unclear. The objective of this analysis was to model the potential pharmacoeconomic value of using patiromer and spironolactone in patients with a history of hyperkalemia that prevents them from utilizing spironolactone.MethodsWe performed a cost-effectiveness analysis of treatment with patiromer, spironolactone, and an angiotensin-converting enzyme inhibitor (ACEI) in patients with New York Heart Association (NYHA) class III-IV HF compared with ACEI alone. A Markov model was constructed to simulate a cohort of 65-year-old patients diagnosed with HF from the payer perspective across the lifetime horizon. Clinical inputs were derived from the RALES and OPAL-HK randomized trials of spironolactone and patiromer, respectively. Utility estimates and costs were derived from the literature and list prices. Outcomes assessed included hospitalization, life expectancy, and quality-adjusted life-years (QALYs), costs, and the incremental cost-effectiveness ratio (ICER). One-way and probability sensitivity analyses were performed to test the robustness of the model findings.ResultsTreatment with patiromer-spironolactone-ACEI was projected to increase longevity compared with ACEI alone (5.29 vs. 4.62 life-years gained, respectively), greater QALYs (2.79 vs. 2.60), and costs (US$28,200 vs. US$18,200), giving an ICER of US$52,700 per QALY gained. The ICERs ranged from US$40,000 to US$85,800 per QALY gained in 1-way sensitivity analyses.ConclusionOur results suggest that the use of spironolactone-patiromer-ACEI may provide clinical benefit and good economic value in patients with NYHA class III-IV HF unable to tolerate spironolactone due to hyperkalemia.

Dataset Information

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

Publications

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

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