Maintained renin-angiotensin-aldosterone system inhibitor therapy with sodium zirconium cyclosilicate following a hyperkalaemia episode: a multicountry cohort study.

Background: This observational cohort study compared the likelihood of maintained (stabilized/up-titrated) renin-angiotensin-aldosterone system inhibitor (RAASi) therapy at 6 months following hyperkalaemia in patients with chronic kidney disease (CKD) and/or heart failure (HF) from the USA, Japan and Spain who received sodium zirconium cyclosilicate (SZC) for at least 120 days, relative to those with no prescription for a potassium (K+) binder. Methods: Using health registers and hospital medical records, patients with CKD and/or HF receiving RAASi therapy who experienced a hyperkalaemia episode were identified. Propensity score (PS) matching (1:4) was applied to balance the SZC cohort to the no K+ binder cohort on baseline characteristics. Logistic regression analysis was performed to compare the odds of maintained RAASi therapy at 6 months in the SZC versus no K+ binder cohorts. Results: The PS-matched SZC cohort included 565 (USA), 776 (Japan) and 56 (Spain) patients; the no K+ binder cohort included 2068, 2629 and 203 patients, respectively. At 6 months, 68.9% (USA), 79.9% (Japan) and 69.6% (Spain) in the SZC cohorts versus 53.1% (USA), 56.0% (Japan) and 48.3% (Spain) in the no K+ binder cohorts had maintained RAASi therapy. Meta-analysed across countries, the odds ratio of maintained RAASi therapy in the SZC cohort versus no K+ binder cohort was 2.56 (95% confidence interval 1.92-3.41; P < .0001). Conclusions: In routine clinical practice across three countries, patients treated with SZC were substantially more likely to maintain guideline-concordant RAASi therapy at 6 months following hyperkalaemia relative to patients with no K+ binder treatment.

Randomised, blinded, cross-over evaluation of the palatability of and preference for different potassium binders in participants with chronic hyperkalaemia in the USA, Canada and Europe: the APPETIZE study.

OBJECTIVES: Traditional potassium (K+) binders for treating hyperkalaemia are unpalatable and poorly tolerated. Newer K+ binders are reportedly better tolerated; however, no published data describe their palatability, a determinant of long-term adherence. This study evaluated the palatability of and preference for three K+ binders: sodium and calcium polystyrene sulfonate (S/CPS), sodium zirconium cyclosilicate (SZC) and calcium patiromer sorbitex (patiromer). DESIGN: Phase 4, randomised, participant-blinded, cross-over study. Participants were randomised to one of six taste sequences and, using a 'sip and spit' approach, tasted each K+ binder before completing a survey. SETTING: 17 centres across the USA, Canada and European Union. PARTICIPANTS: 144 participants with chronic kidney disease, hyperkalaemia and no recent use of K+ binders. MAIN OUTCOME MEASURES: For the primary (USA) and key secondary (Canada and European Union) endpoints, participants rated palatability attributes (taste, texture, smell and mouthfeel) and willingness to take each K+ binder on a scale of 0-10 (rational evaluation). Feelings about each attribute, and the idea of taking the product once daily, were evaluated using a non-verbal, visual measure of emotional response. Finally, participants ranked the K+ binders according to palatability. RESULTS: In each region, SZC and patiromer outperformed S/CPS on overall palatability (a composite of taste, texture, smell and mouthfeel), based on rational evaluation and emotional response. Taking the product once daily was more appealing for SZC and patiromer, creating greater receptivity than the idea of taking S/CPS. The emotional response to mouthfeel had the strongest influence on feelings about taking each product. In each region, a numerically greater proportion of participants ranked SZC as the most preferred K+ binder versus patiromer or S/CPS. CONCLUSIONS: Preference for more palatable K+ binders such as SZC and patiromer may provide an opportunity to improve adherence to long-term treatment of hyperkalaemia. TRIAL REGISTRATION NUMBER: NCT04566653.

Rationale and design of CONTINUITY: a Phase 4 randomized controlled trial of continued post-discharge sodium zirconium cyclosilicate treatment versus standard of care for hyperkalemia in chronic kidney disease.

Background: Individuals with chronic kidney disease (CKD) hospitalized with hyperkalemia are at risk of hyperkalemia recurrence and re-hospitalization. We present the rationale and design of CONTINUITY, a study to examine the efficacy of continuing sodium zirconium cyclosilicate (SZC)-an oral, highly selective potassium (K+) binder-compared with standard of care (SoC) on maintaining normokalemia and reducing re-hospitalization and resource utilization among participants with CKD hospitalized with hyperkalemia. Methods: This Phase 4, randomized, open-label, multicenter study will enroll adults with Stage 3b-5 CKD and/or estimated glomerular filtration rate <45 mL/min/1.73 m2, within 3 months of eligibility screening, hospitalized with a serum potassium (sK+) level of >5.0-≤6.5 mmol/L, without ongoing K+ binder treatment. The study will include an in-hospital phase, where participants receive SZC for 2-21 days, and an outpatient (post-discharge) phase. At discharge, participants with sK+ 3.5-5.0 mmol/L will be randomized (1:1) to SZC or SoC and monitored for 180 days. The primary endpoint is the occurrence of normokalemia at 180 days. Secondary outcomes include incidence and number of hospital admissions or emergency department visits both with hyperkalemia as a contributing factor, and renin-angiotensin-aldosterone system inhibitor down-titration. The safety and tolerability of SZC will be evaluated.Ethics approval has been received from all relevant ethics committees. Enrollment started March 2022 and the estimated study end date is December 2023. Conclusions: This study will assess the potential of SZC versus SoC in managing people with CKD and hyperkalemia post-discharge. Trial registration: ClinicalTrials.gov identifier: NCT05347693; EudraCT: 2021-003527-14, registered on 19 October 2021.

Drug treatment patterns and work productivity in chronic kidney disease patients with anemia in China: Cross sectional analysis of real-world data.

BACKGROUND: We explored the association of anemia severity in patients with chronic kidney disease (CKD) and anemia treatment with work productivity in China. METHODS: Cross-sectional survey data from Chinese physicians and their CKD patients were collected in 2015. Physicians recorded demographics, disease characteristics, and treatment. Patients completed the Work Productivity and Activity Impairment questionnaire. Data were stratified by dialysis-dependence, hemoglobin (Hb) level, and anemia treatment. RESULTS: Based on data from 1,052 patients (704 non-dialysis-dependent [NDD] and 348 dialysis-dependent [DD] patients), prescribed anemia treatment differed significantly across Hb levels (P < 0.001). In NDD patients, anemia treatment also differed significantly by on-treatment Hb level (P < 0.001). In treated NDD patients with Hb < 10 g/ dL, Hb 10 to 12 g/dL, and Hb > 12 g/dL, 31%, 59%, and 38% of patients, respectively, were prescribed oral iron, and 34%, 19%, and 0% of patients, respectively, were prescribed oral iron with erythropoiesis-stimulating agents (ESA). NDD patients were less likely to be prescribed any anemia treatment, and ESA specifically, than DD patients. When treated, 67% and 45% of NDD and DD patients, respectively, had Hb ≥ 10 g/dL (P < 0.001). Overall work and activity impairment differed significantly across Hb levels in NDD and DD patients, with the least impairment observed at the highest Hb level. CONCLUSION: Approximately 40% of NDD patients and 60% of DD patients receiving anemia treatment had Hb < 10 g/dL. Compared with mild anemia patients, severe anemia patients were more likely to be treated for anemia and have impaired work productivity. Chinese CKD patients could benefit from improved anemia treatment.

Characteristics, Symptom Severity, and Experiences of Patients Reporting Chronic Kidney Disease in the PatientsLikeMe Online Health Community: Retrospective and Qualitative Study.

BACKGROUND: Chronic kidney disease (CKD) is a major global health burden, and is associated with increased adverse outcomes, poor quality of life, and substantial health care costs. While there is an increasing need to build patient-centered pathways for improving CKD management in clinical care, data in this field are scarce. OBJECTIVE: The aim of this study was to understand patient-reported experiences, symptoms, outcomes, and treatment journeys among patients with CKD through a retrospective and qualitative approach based on data available through PatientsLikeMe (PLM), an online community where patients can connect and share experiences. METHODS: Adult members (aged ≥18 years) with self-reported CKD within 30 days of enrollment, who were not on dialysis, and registered between 2011 and 2018 in the PLM community were eligible for the retrospective study. Patient demographics and disease characteristics/symptoms were collected from this retrospective data set. Qualitative data were collected prospectively through semistructured phone interviews in a subset of patients, and questions were oriented to better understand patients' experiences with CKD and its management. RESULTS: The retrospective data set included 1848 eligible patients with CKD, and median age was 56 years. The majority of patients were female (1217/1841, 66.11%) and most were US residents (1450/1661, 87.30%). Of the patients who reported comorbidities (n=1374), the most common were type 2 diabetes (783/1374, 56.99%), hypertension (664/1374, 48.33%), hypercholesterolemia (439/1374, 31.95%), and diabetic neuropathy (376/1374, 27.37%). The most commonly reported severe or moderate symptoms in patients reporting these symptoms were fatigue (347/484, 71.7%) and pain (278/476, 58.4%). In the qualitative study, 18 eligible patients (13 females) with a median age of 60 years and who were mainly US residents were interviewed. Three key concepts were identified by patients to be important to optimal care and management: listening to patient needs, coordinating health care across providers, and managing clinical care. CONCLUSIONS: This study provides a unique source of real-world information on the patient experience of CKD and its management by utilizing the PLM network. The results reveal the challenges these patients face living with an array of symptoms, and report key concepts identified by patients that can be used to further improve clinical care and management and inform future CKD studies.

Predictors of Bleeding in Patients with Symptomatic Peripheral Artery Disease: A Cohort Study Using The Health Improvement Network in the United Kingdom.

The purpose of this analysis was to assess potential predictors of intra-cranial bleeding (ICB) and gastrointestinal bleeding (GIB) in patients with symptomatic peripheral artery disease (PAD) in UK primary care. Patients with symptomatic PAD diagnosed from 2000 to 2010 were identified from The Health Improvement Network (THIN; N = 28,484). A nested case-control analysis, adjusted for potential confounders, was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for potential predictors of ICB or GIB. For GIB, follow-up was restricted to Hospital Episode Statistics-linked THIN practices. Median follow-up was 6 years. For ICB (153 cases), the OR (95% CI) was 3.85 (1.33-11.13) for previous ICB, 0.90 (0.61-1.34) for treated hypertension, 1.59 (0.65-3.87) for untreated hypertension and 1.38 (0.80-2.36) for current smoking. ORs for ICB were 0.78 (0.50-1.21), 0.40 (0.09-1.82) and 1.27 (0.47-3.47) with use of acetylsalicylic acid (ASA), clopidogrel and warfarin monotherapy, respectively, compared with non-use of such therapy. For GIB (506 cases), the OR was 1.40 (1.05-1.86) for peptic ulcer disease, 3.20 (1.81-5.64) for dual anti-platelet therapy use, 1.96 (1.46-2.64) for non-steroidal anti-inflammatory drug (NSAID) use and 1.01 (0.80-1.28) for proton pump inhibitor use. ORs for GIB were 1.78 (1.39-2.30), 2.03 (1.05-3.93) and 1.25 (0.72-2.16) with ASA, clopidogrel and warfarin monotherapy, respectively, compared with non-use. Previous ICB was a risk factor for ICB. Use of anti-platelet therapy or NSAIDs increased GIB risk. Identifying bleeding predictors could help optimize treatment strategies for patients with PAD.

Time trends in peripheral artery disease incidence, prevalence and secondary preventive therapy: a cohort study in The Health Improvement Network in the UK.

OBJECTIVES: To assess time trends in symptomatic peripheral artery disease (PAD) incidence and prevalence, and secondary preventive therapy. DESIGN: Cohort study using The Health Improvement Network. SETTING: UK primary care. PARTICIPANTS: Individuals aged 50-89 years identified annually between 2000 and 2014. Participants with symptomatic PAD were identified using Read codes. OUTCOME MEASURES: Incidence and prevalence of symptomatic PAD from 2000 to 2014, overall and by sex and age. Proportion of patients prescribed secondary preventive therapy with acetylsalicylic acid (ASA), clopidogrel, an ACE inhibitor, an angiotensin receptor blocker (ARB) and/or a statin. RESULTS: The incidence of symptomatic PAD per 10 000 person-years decreased over time, from 38.6 (men: 51.0; women: 28.7) in 2000 to 17.3 (men: 23.1; women: 12.4) in 2014. The prevalence of symptomatic PAD decreased from 3.4% (men: 4.5%; women: 2.5%) in 2000 to 2.4% (men: 3.1%; women: 1.7%) in 2014. Incidence and prevalence decreases were observed in all age groups. The proportions of patients prescribed ASA monotherapy, clopidogrel monotherapy and dual antiplatelet therapy in the 2 months after PAD diagnosis were 42.7%, 2.9% and 2.5%, respectively, during 2000-2003, and 44.7%, 11.0% and 5.2%, respectively, during 2012-2014. For ACE inhibitor/ARB therapy and statins, proportions in the 2 months after diagnosis were 30.2% and 31.2%, respectively, during 2000-2003, and 45.1% and 65.9%, respectively, during 2012-2014. CONCLUSION: The incidence and prevalence of symptomatic PAD diagnosed in UK primary care are decreasing. A large proportion of the population with PAD in clinical practice does not receive guideline-recommended secondary prevention therapy.

Cardiovascular outcomes for patients with symptomatic peripheral artery disease: A cohort study in The Health Improvement Network (THIN) in the UK.

Background Few data are available on risk factors and associations with outcomes in symptomatic peripheral artery disease (PAD) populations in primary care. We assessed characteristics and cardiovascular outcomes in patients with and those without symptomatic peripheral artery disease in UK primary care, and quantified risk factors for cardiovascular outcomes in patients with peripheral artery disease. Methods Among patients in The Health Improvement Network (THIN) aged 50-89 years in 2000-2010, a symptomatic peripheral artery disease cohort ( n = 28,484) and a matched comparison cohort without peripheral artery disease ( n = 113,940) were identified using Read codes. Cox proportional hazard ratios (HRs) and 95% confidence intervals (CIs) for cardiovascular outcomes were calculated, adjusted for potential confounders. Results The incidence of all-cause death per 1000 person-years was 83.22 and 50.46 in the peripheral artery disease and non-peripheral artery disease cohort, respectively (HR 1.41; 95% CI 1.68-1.43). The incidence of composite cardiovascular outcome (myocardial infarction, ischaemic stroke or cardiovascular-related death) per 1000 person-years was 31.87 and 14.63 in the peripheral artery disease and non-peripheral artery disease cohort, respectively (HR 1.71; 95% CI 1.65-1.77). Risk factors for composite cardiovascular outcome in patients with peripheral artery disease were older age (≥75 years vs. 50-64 years: HR 2.37; 95% CI 2.20-2.55), current smoking (1.26; 1.17-1.35), comorbid diabetes (1.42; 1.32-1.52), heart failure (1.31; 1.20-1.44), atrial fibrillation (1.32; 1.18-1.47, previous myocardial infarction (1.29; 1.20-1.39) and previous ischaemic stroke (1.77; 1.63-1.93). Conclusion Patients with symptomatic peripheral artery disease in a clinical practice population have a high risk of death and cardiovascular-related outcomes. Minimising risk is important in the ongoing management of these patients.