Heart Failure and Edema Costs in Patiromer and SZC Users.

BACKGROUND: Previous work suggested differences between patients taking patiromer or sodium zirconium cyclosilicate (SZC) in real-world risk of heart failure (HF) hospitalizations and edema hospitalizations or emergency department (ED) visits (edema events). We further investigated these differences to assess economic importance. Retrospective study using published event rates and mean costs derived from Optum's de-identified Clinformatics® Data Mart (CDM) Database. METHODS: We designed a model to estimate adjusted economic offsets that combined respective patiromer and SZC HF hospitalization (25.1 and 35.8; difference 10.7 [95% confidence interval [CI]2: 2.6-18.8]) and edema event (3.4 and 7.1; difference 3.6 [95% CI: 1.7-7.1]) rates/100 person-years from the original published work with costs from our parallel data extract spanning 2019-2021, adjusted to 2021 US dollars. RESULTS: In a base case of mean HF hospitalization, edema event, and 30-count potassium-binder prescription costs from our data extract, the estimated mean savings with patiromer was $1,428 per person per year (PPPY; 95% CI: -$1,508 to $4,652). Respective costs PPPY for patiromer vs SZC were $8,526 vs $12,622 (difference $4,096 [95% CI: $1,160-$7,320]) for HF hospitalization and edema events, and $10,649 vs $7,981 (difference -$2,668) for potassium binders, totaling $19,175 for patiromer vs $20,603 for SZC. CONCLUSION: With differing drug costs, hospitalization and ED costs offset this difference when event rates were numerically small. Model outcomes were driven by HF hospitalization cost and least influenced by edema ED visit cost. A limitation was that the CDM data extract may differ from the original work.

Epidemiology and risk factors for hyperkalaemia in heart failure.

Patients with heart failure (HF), particularly those with impaired renal function receiving renin-angiotensin-aldosterone system inhibitors (RAASis), are at risk of hyperkalaemia; when hyperkalaemia is severe, this can have serious clinical consequences. The incidence, prevalence, and risk factors for hyperkalaemia reported in randomized trials of RAASis may not reflect clinical practice due to exclusion of patients with elevated serum potassium (sK+ ) or severe renal impairment: information on patients managed in routine clinical care is important to understanding the actual burden of hyperkalaemia. This paper reviews the available clinical epidemiology data on hyperkalaemia in HF and considers areas requiring further research. Observational studies published since 2017 that focused on hyperkalaemia, included patients with HF, and had ≥1000 participants were considered. Hyperkalaemia occurrence in HF varied widely from 7% to 39% depending on the setting, HF severity, follow-up length, and concomitant medications. Rates were lowest in patients with newly diagnosed HF and highest in patients with greater disease severity; comorbidities, such as chronic kidney disease and diabetes, and RAASi use, reflected commonly identified risk factors for hyperkalaemia in patients with HF. Hyperkalaemia was most often mild; however, from the limited data available, persistence of mild hyperkalaemia was associated with an increased risk of mortality and major adverse cardiovascular events. There were also limited data available on the progression of hyperkalaemia. Recurrence was common, occurring in one-quarter to two-fifths of hyperkalaemia cases. Despite HF guidelines recommending close monitoring of sK+ , 55-93% of patients did not receive appropriate testing before or after initiation of RAASi or in follow-up to moderate/severe hyperkalaemia detection. Many of the observational studies were retrospective and from a single country. There is a need for international, prospective, longitudinal, observational studies, such as the CARE-HK in HF study (NCT04864795), to understand hyperkalaemia's prevalence, incidence, and severity; to identify and characterize cases that persist, progress, and recur; to highlight the importance of sK+ monitoring when using RAASi; and to assess the impact of newer HF therapies and potassium binders in clinical practice. Data from both clinical trials and observational studies with adjustments for confounding variables will be needed to assess the contribution of hyperkalaemia to clinical outcomes.

Evaluation of longer- vs short-term use of patiromer on health care resource utilization in the patiromer longer-term use evaluation (VALUE) study.

BACKGROUND: Studies suggest that continuous long-term use of patiromer by patients with hyperkalemia is associated with less health care resource utilization compared with not using potassium binders. OBJECTIVE: To retrospectively evaluate health care resource utilization and costs with longer-term adherent vs short-term use of patiromer. METHODS: Time-restricted extracts from Optum's de-identified Clinformatics® Data Mart Database (CDM; January 2016-May 2019) and Symphony Health (SHA; January 2016-September 2018) deidentified databases were analyzed. Both include participants enrolled in commercial and privatized public insurance programs (SHA includes some government programs). Both integrate health care claims data from medical and pharmacy claims. Patients aged 18 years or older with hyperkalemia and an index patiromer prescription were selected. Patiromer use was identified as short-term (<2 months) and any fill quantity or adherent longer-term with claims for at least 2 consecutive months and fill quantities of at least 80% of the total days. Groups were matched on multiple categorical covariates to control for demographic variables, baseline characteristics, and markers of disease severity. Random sampling without replacement was performed 50 times to identify 50 sets of patients matched from the short-term cohort to the longer-term cohort. Health care costs/charges and encounters were compared for a 6-month post-index period using t-tests. RESULTS: Of the CDM patients, 1,267 (40.2%) vs 1,887 (59.8%) and of the SHA patients, 2,234 (35.1%) vs 4,132 (64.9%) experienced longer-term vs short-term patiromer use, respectively. Patient sampling selected 242 and 485 patient-matched pairs from CDM and SHA databases, respectively. At 6 months post-index in longer-term vs short-term patiromer groups (P < 0.0001 for all differences shown), respective mean medical and prescription costs/charges were $42,000 vs $54,311 (-$12,311) and $6,816 vs $4,786 (+$2,030), respectively, for CDM patients and $75,147 vs $84,414 (-$9,267) and $4,689 vs $3,736 (+$953) for SHA patients. In the CDM database, medical costs were lower for longer-term vs short-term cohorts for end-stage renal disease services charges ($10,342 vs $14,976 [-$4,634]), inpatient charges ($15,789 vs $21,473 [-$5,684]), and office visit charges ($10,152 vs $13,152 [-$3,000]). Patient out-of-pocket costs ($658 vs $420 [+$238]) and total prescription charges ($6,158 vs $4,366 [+$1,792]) were higher for the longer-term cohort of CDM patients, with similar findings in the SHA dataset. CONCLUSIONS: Adherent, longer-term use of patiromer is associated with significantly lower medical costs offsetting higher prescription costs, driven by the largest changes in inpatient and clinic services at CDM and SHA, respectively. This illustrates an economic value of longer-term adherence to patiromer.

Social determinants of patiromer adherence and abandonment: An observational, retrospective, real-world claims analysis.

BACKGROUND: Hyperkalemia is a frequent and serious complication in chronic kidney disease (CKD) that can impede continuation of beneficial evidence-based therapies. Recently, novel therapies such as patiromer have been developed to treat chronic hyperkalemia, but their optimal utility hinges on adherence. Social determinants of health (SDOH) are critically important and can impact both medical conditions and treatment prescription adherence. This analysis examines SDOH and their influence on adherence to patiromer or abandonment of prescriptions for hyperkalemia treatment. METHODS: This was an observational, retrospective, real-world claims analysis of adults with patiromer prescriptions and 6- and 12-months pre- and post-index prescription data in Symphony Health's Dataverse during 2015-2020, and SDOH from census data. Subgroups included patients with heart failure (HF), hyperkalemia-confounding prescriptions, and any CKD stages. Adherence was defined as >80% of proportion of days covered (PDC) for ≥60 days and ≥6 months, and abandonment as a portion of reversed claims. Quasi-Poisson regression modeled the impact of independent variables on PDC. Abandonment models used logistic regression, controlling for similar factors and initial days' supply. Statistical significance was p<0.05. RESULTS: 48% of patients at 60 days and 25% at 6 months had a patiromer PDC >80%. Higher PDC was associated with older age, males, Medicare/Medicaid coverage, nephrologist prescribed, and those receiving renin-angiotensin-aldosterone system inhibitors. Lower PDC correlated with higher out-of-pocket cost, unemployment, poverty, disability, and any CKD stage with comorbid HF. PDC was better in regions with higher education and income. CONCLUSIONS: SDOH (unemployment, poverty, education, income) and health indicators (disability, comorbid CKD, HF) were associated with low PDC. Prescription abandonment was higher in patients with prescribed higher dose, higher out-of-pocket costs, those with disability, or designated White. Key demographic, social, and other factors play a role in drug adherence when treating life-threatening abnormalities such as hyperkalemia and may influence patient outcomes.

Real-world clinical burden and economic assessment associated with hyperkalaemia in a large integrated healthcare system: a retrospective analysis.

BACKGROUND: Hyperkalaemia (HK) is a serious and potentially life-threatening condition. Both acute and chronic conditions may alter potassium homeostasis. Our aim is to describe HK incidence, clinical outcomes, and associated resource use within a large, integrated healthcare system. METHODS: Adult patients seen at Intermountain Healthcare facilities with a serum potassium (sK) result between January 1, 2003 and December 31, 2018 were retrospectively studied. Descriptive assessment of a population with detected HK, defined by any sK > 5.0 mmol/L and HK frequency and severity to associated resource use and characteristics of HK predictors were made. Multivariable Cox hazard regression was used to evaluate HK to outcomes. RESULTS: Of 1,208,815 patients included, 13% had HK. Compared to no-HK, HK patients were older (60 ± 18 vs 43 ± 18 years, P < 0.001), male (51% vs 41%, P < 0.001), and had greater disease burden (Charlson Comorbidity Index 3.5 ± 2.8 vs 1.7 ± 1.4, P < 0.001). At 3 years, more HK patients experienced major adverse cardiovascular events (MACEs) (19 vs 3%, P < 0.001), persisting post-adjustment (multivariable hazard ratio = 1.60, P < 0.001). They incurred higher costs for emergency department services ($552 ± 7,574 vs $207 ± 1,930, P < 0.001) and inpatient stays ($10,956 ± 93,026 vs $1,477 ± 21,423, P < 0.001). HyperK Risk Scores for the derivation and validation cohorts were: 44% low-risk, 45% moderate-risk, 11% high-risk. Strongest HK predictors were renal failure, dialysis, aldosterone blockers, diabetes, and smoking. CONCLUSION: Within this large system, HK was associated with a large clinical burden, affecting over 1 in 10 patients; HK was also associated with increased 3-year MACE risk and higher medical costs. Although risk worsened with more severe or persistently recurring HK, even mild or intermittent HK episodes were associated with significantly greater adverse clinical outcomes and medical costs. The HyperK Score predicted patients who may benefit from closer management to reduce HK risk and associated costs. It should be remembered that our assumptions are valid only for detected HK and not HK per se.

Frequency and clinical impact of hyperkalaemia within a large, modern, real-world heart failure population.

AIMS: This analysis qualitatively describes the impact of hyperkalaemia (HK) and renin-angiotensin-aldosterone system inhibitor (RAASi) use on clinical outcomes in patients with heart failure (HF). METHODS AND RESULTS: Patients were included if they were ≥18 years old; had a serum potassium result between 1 January 2003 and 3 December 2018; had ≥2 separate, non-urgent care or emergency department encounters; and had an HF diagnosis. Criteria were met by 52 253 patients; 48 333 had sufficient follow-up for analysis. Patients were stratified by the presence/absence of HK (serum potassium >5.0 mmol/L) (n = 31 619 and n = 20 634, respectively) and by baseline left ventricular ejection fraction (LVEF) ≤40% or >40%. Compared with patients without HK (no-HK), those with HK had significantly higher rates of baseline cardiovascular risk factors, prior diagnoses, and greater RAASi use in both baseline and follow-up periods. Assessed outcomes included RAASi use, rate of 3 year major adverse cardiovascular events (MACE), and individual component rates. Between baseline and follow-up analyses, the proportion of patients on RAASi decreased by 5% in patients with HK but increased by 20% in no-HK patients. Overall, MACE and death were consistently highest in the presence of HK without RAASi treatment (63% and 62%, respectively) and lowest in no-HK but on RAASi (25% and 21%, respectively). After complete multivariable adjustment, these trends were consistent regardless of baseline LVEF. CONCLUSIONS: In this large, real-world HF population, HK was common and linked to baseline clinical risk factors, declining use of RAASi treatment, and an increase in future MACE, regardless of baseline LVEF. Both HK and reduced RAASi use were independent predictors of future MACE.

HYPHYCA: a prospective study in 613 patients conducting a comprehensive analysis for predictive factors of physiological 18F-FDG anal uptake.

BACKGROUND: Anal cancer is a relatively rare tumor of which incidence increases in developed countries. 18F-FDG PET has been increasingly used for its post radio-chemotherapy evaluation. However, several authors have reported the risk of local false-positive findings leading to low specificity and positive predictive values. These false-positive results could be due to post-radiotherapy inflammation or infection but certainly also to physiological anal canal uptake that is observed on a regular basis in clinical practice. The purpose of this prospective study (NCT03506529; HYPHYCA) was therefore to seek predictive factors of physiological anal canal hypermetabolism. MATERIALS AND METHODS: Over a 2-month period, patients aged 18 years old and more, referred for 18F-FDG PET-CT at two EARL-accredited PET centers were included, after obtaining their informed and written consent. They were asked to fill in a questionnaire including seven closed questions about usual intestinal transit, ongoing medications relative to intestinal transit, history of digestive, and anal and/or pelvic diseases. Age, gender, and body mass index (BMI) were recorded. A single nuclear medicine physician visually and quantitatively analyzed anal canal uptake (SUVmax_EARL) and assessed visual rectal content (air, feces, or both) and the largest rectal diameter (mm). RESULTS: Six hundred and thirteen patients were included (sex ratio F/M = 0.99) and 545 (89%) questionnaires were entirely completed. Significantly more males presented anal canal hypermetabolism (sex ratio (M/F) = 1.18 versus 0.85, p = 0.048). Moreover, patients with anal canal hypermetabolism had higher BMI (27.6 (5.7) kg/m2 versus 23.9 (4.5) kg/m2, p < 0.0001), higher rate of hemorrhoid history (43% versus 27%, p = 0.016), and higher rate of rectum filled with only feces (21% versus 12%, p = 0.019) as compared to patients with no anal canal uptake. On logistic regression, all these variables were found to be independent predictors of the occurrence of an anal canal hypermetabolism. Odds ratio were 1.16 (1.12-1.20) per unit of BMI (kg/m2) (p < 0.0001), 1.48 (1.04-2.11) for males (p = 0.030), 1.64 (1.10-2.45) for hemorrhoids history (p = 0.016), and 1.94 (1.147-3.22) for the rectum filled with only feces (p = 0.010). CONCLUSION: According to our study, the predictive factors of physiological anal canal hypermetabolism are high BMI, male gender, hemorrhoid history, and rectum filled with only feces. This may pave the way to a more specific interpretation of post radio-chemotherapy PET evaluations of anal canal cancer, provided that other studies are conducted in this specific population. TRIAL REGISTRATION: This prospective study was registered at Clinicaltrial.gov: NCT03506529; HYPHYCA on April 24, 2018.

The clinical and economic impact of cytomegalovirus infection in recipients of hematopoietic stem cell transplantation.

BACKGROUND: CMV infection (CMV-I) remains an important complication of hematopoietic stem cell transplantation (HSCT). METHODS: This was a retrospective, single-center cohort study in HSCT recipients. Primary outcomes were adjusted cost and all-cause mortality. Secondary analyses investigated CMV risk factors and the effect of serostatus. RESULTS: Overall, 690 transplant episodes were included (allogeneic [n = 310]; autologous [n = 380]). All received preemptive CMV antiviral therapy at first detectable DNAemia. CMV-I occurred in 34.8% of allogeneic and 2.1% of autologous transplants; median time to onset was 45 days. In allogeneic HSCT recipients, the primary risk factor for CMV-I was CMV donor/recipient (D/R) serostatus. In a Markov multi-state model for allogeneic HSCT recipients, the hazard ratio for CMV-I and relapse was 1.5 (95% CI 0.8-2.8) and for CMV-I and mortality 2.4 (95% CI 0.9-6.5). In a multivariable model for all patients, CMV-I was associated with increased total cost (coefficient = 0.21, estimated incremental daily cost USD $500; P = 0.02). Cost was attenuated in allogeneic HSCT recipients (coefficient = 0.13, USD $699 vs $613, or $24 892 per transplant episode; P = 0.23). CMV disease (CMV-D) complicated 29.6% of CMV-I events in allogeneic HSCT recipients, but was not associated with an incrementally increased adjusted risk of mortality compared with CMV-I alone. CMV-I (56.4%) and CMV-D (19.8%) were significantly overrepresented in D-/R+ serostatus HSCT recipients, and mortality was higher in R+ HSCT recipients. CONCLUSIONS: Despite early preemptive antiviral treatment, CMV-I impacts clinical outcomes and cost after HSCT, but the impact on cost is less pronounced in allogeneic HSCT recipients compared with autologous HSCT recipients.