Epidemiology and outcomes in patients with anemia of CKD not on dialysis from a large US healthcare system database: a retrospective observational study.

BACKGROUND: Optimal management of anemia of chronic kidney disease (CKD) remains controversial. This retrospective study aimed to describe the epidemiology and selected clinical outcomes of anemia in patients with CKD in the US. METHODS: Data were extracted from Henry Ford Health System databases. Adults with stages 3a-5 CKD not on dialysis (estimated glomerular filtration rate < 60 mL/min/1.73m2) between January 1, 2013 and December 31, 2017 were identified. Patients on renal replacement therapy or with active cancer or bleeding were excluded. Patients were followed for ≥12 months until December 31, 2018. Outcomes included incidence rates per 100 person-years (PY) of anemia (hemoglobin < 10 g/dL), renal and major adverse cardiovascular events, and of bleeding and hospitalization outcomes. Adjusted Cox proportional hazards models identified factors associated with outcomes after 1 and 5 years. RESULTS: Among the study cohort (N = 50,701), prevalence of anemia at baseline was 23.0%. Treatments used by these patients included erythropoiesis-stimulating agents (4.1%), iron replacement (24.2%), and red blood cell transfusions (11.0%). Anemia incidence rates per 100 PY in patients without baseline anemia were 7.4 and 9.7 after 1 and 5 years, respectively. Baseline anemia was associated with increased risk of renal and major cardiovascular events, hospitalizations (all-cause and for bleeding), and transfusion requirements. Increasing CKD stage was associated with increased risk of incident anemia, renal and major adverse cardiovascular events, and hospitalizations. CONCLUSIONS: Anemia was a prevalent condition associated with adverse renal, cardiovascular, and bleeding/hospitalization outcomes in US patients with CKD. Anemia treatment was infrequent.

Cardiovascular and mortality benefits of sodium-glucose co-transporter-2 inhibitors in patients with type 2 diabetes mellitus: CVD-Real Catalonia.

BACKGROUND: Evidence from prospective cardiovascular (CV) outcome trials in type 2 diabetes (T2DM) patients supports the use of sodium-glucose co-transporter-2 inhibitors (SGLT2i) to reduce the risk of CV events. In this study, we compared the risk of several CV outcomes between new users of SGLT2i and other glucose-lowering drugs (oGLDs) in Catalonia, Spain. METHODS: CVD-REAL Catalonia was a retrospective cohort study using real-world data routinely collected between 2013 and 2016. The cohorts of new users of SGLT2i and oGLDs were matched by propensity score on a 1:1 ratio. We compared the incidence rates and hazard ratio (HR) for all-cause death, hospitalization for heart failure, chronic kidney disease, and modified major adverse CV event (MACE; all-cause mortality, myocardial infarction, or stroke). RESULTS: After propensity score matching, 12,917 new users were included in each group. About 27% of users had a previous history of CV disease. In the SGLT2i group, the exposure time was 60% for dapagliflozin, 26% for empagliflozin and 14% for canagliflozin. The use of SGLT2i was associated with a lower risk of heart failure (HR: 0.59; 95% confidence interval [CI] 0.47-0.74; p < 0.001), all-cause death (HR = 0.41; 95% CI 0.31-0.54; p < 0.001), all-cause death or heart failure (HR = 0.55; 95% CI 0.47-0.63; p < 0.001), modified MACE (HR = 0.62; 95% CI 0.52-0.74; p < 0.001), and chronic kidney disease (HR = 0.66; 95% CI 0.54-0.80; p < 0.001). CONCLUSIONS: In this large, retrospective observational study of patients with T2DM from a Catalonia, initiation of SGLT-2i was associated with lower risk of mortality, as well as heart failure and CKD.

Cardiovascular outcomes with sodium-glucose cotransporter-2 inhibitors vs other glucose-lowering drugs in 13 countries across three continents: analysis of CVD-REAL data.

BACKGROUND: Randomized, controlled cardiovascular outcome trials may not be fully representative of the management of patients with type 2 diabetes across different geographic regions. We conducted analyses of data from the multinational CVD-REAL consortium to determine the association between initiation of sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and cardiovascular outcomes, including subgroup analyses based on patient characteristics. METHODS: De-identified health records from 13 countries across three continents were used to identify patients newly-initiated on SGLT-2i or other glucose-lowering drugs (oGLDs). Propensity scores for SGLT-2i initiation were developed in each country, with 1:1 matching for oGLD initiation. In the matched groups hazard ratios (HRs) for hospitalization for heart failure (HHF), all-cause death (ACD), the composite of HHF or ACD, myocardial infarction (MI) and stroke were estimated by country, and pooled using a weighted meta-analysis. Multiple subgroup analyses were conducted across patient demographic and clinical characteristics to examine any heterogeneity in treatment effects. RESULTS: Following matching, 440,599 new users of SGLT-2i and oGLDs were included in each group. Mean follow-up time was 396 days for SGLT-2i initiation and 406 days for oGLDs initiation. SGLT-2i initiation was associated with a lower risk of HHF (HR: 0.66, 95%CI 0.58-0.75; p < 0.001), ACD (HR: 0.52, 95%CI 0.45-0.60; p < 0.001), the composite of HHF or ACD (HR: 0.60, 95%CI 0.53-0.68; p < 0.001), MI (HR: 0.85, 95%CI 0.78-0.92; p < 0.001), and stroke (HR: 0.78, 95%CI 0.72-0.85; p < 0.001); regardless of patient characteristics, including established cardiovascular disease, or geographic region. CONCLUSIONS: This CVD-REAL study extends the findings from the SGLT-2i clinical trials to the broader setting of an ethnically and geographically diverse population, and across multiple subgroups. Trial registration NCT02993614.

Association of sodium-glucose cotransporter-2 inhibitors with outcomes in type 2 diabetes with reduced and preserved left ventricular ejection fraction: Analysis from the CVD-REAL 2 study.

This study of real-world data from the Maccabi database in Israel compared the risk of heart failure hospitalization (HHF) or death in patients with type 2 diabetes (T2D) initiating sodium-glucose cotransporter-2 (SGLT2) inhibitors versus other glucose-lowering drugs (OGLDs) according to baseline left ventricular (LV) ejection fraction (EF). After propensity-matching patients by baseline EF there were 10 614 episodes of treatment initiation; 57% had diabetes for >10 years, the mean glycated haemoglobin level was 66 mmol/mol (8.2%), ∼43% had cardiovascular disease, ∼7% had heart failure and ∼ 20% had chronic kidney disease. A total of 2876 patients (∼9%) had reduced EF (<50%). Over a mean follow-up of 1.5 years there were 371 HHFs or deaths, 88 (23.7%) in patients with reduced EF. Initiation of SGLT2 inhibitors versus OGLDs was associated with lower risk of HHF or death overall (hazard ratio [HR] 0.57, 95% confidence interval [CI] 0.46-0.70]; P < 0.001) and in patients with both reduced EF (HR 0.61, 95% CI 0.40-0.93) and preserved EF (HR 0.55, 95% CI 0.43-0.70), with no significant heterogeneity (Pinteraction = 0.72). Our findings from real-world clinical practice show that the lower risk of HHF and death associated with use of SGLT2 inhibitors versus OGLDs is consistent in T2D patients with both reduced and preserved EF.

Renal outcomes and all-cause death associated with sodium-glucose co-transporter-2 inhibitors versus other glucose-lowering drugs (CVD-REAL 3 Korea).

AIMS: To investigate the effectiveness of sodium-glucose co-transporter-2 (SGLT2) inhibitors on the risk of progression to end-stage renal disease (ESRD) and all-cause mortality in a broad range of patients with type 2 diabetes (T2D) using a Korean nationwide cohort. MATERIALS AND METHODS: Using data from the Korean National Health Insurance Service database from January 2014 to December 2017, a total of 701 674 patients were identified with T2D. We divided these patients into new users of SGLT2 inhibitors and new users of other glucose-lowering drugs (oGLDs). Using propensity scores, patients in the two groups were matched 1:1. We assessed the risk of ESRD and all-cause death. RESULTS: There were 45 016 patients in each group, and baseline characteristics were well balanced between the groups. The patients' mean age was 58.1 ± 10.6 years and mean estimated glomerular filtration rate (eGFR) was 89.2 ± 27.4 mL/min/1.73m2 , and 8% of patients had proteinuria. We identified 167 incident ESRD cases and 1070 all-cause deaths during follow-up. Use of SGLT2 inhibitors versus oGLDs was associated with a lower risk of ESRD (hazard ratio [HR] 0.47, 95% confidence interval [CI] 0.34 to 0.65) and all-cause death (HR 0.82, 95% CI 0.73 to 0.93). In a subgroup analysis by eGFR, initiation of SGLT2 inhibitor treatment, compared with oGLD treatment, was associated with lower risk of progression to ESRD among patients with eGFR 60 to 90 mL/min/1.73m2 and those with eGFR < 60 mL/min/1.73m2 , and a lower risk of all-cause death was associated with SGLT2 inhibitors versus oGLDs in patients with eGFR ≥90 and 60 to 90 mL/min/1.73m2 . CONCLUSION: In this large nationwide study of Korean patients with T2D, initiation of SGLT2 inhibitors versus oGLDs was associated with lower risk of ESRD and all-cause death.

Assessing the cost-effectiveness of sodium-glucose cotransporter-2 inhibitors in type 2 diabetes mellitus: A comprehensive economic evaluation using clinical trial and real-world evidence.

AIMS: The economic burden of diabetes is driven by the management of vascular complications. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated reductions in cardiovascular and renal complications, including hospitalization for heart failure (HHF) and renal disease progression, in randomized clinical trials. The objective of this study was to evaluate the cost-effectiveness of the SGLT2i class versus standard of care in type 2 diabetes mellitus (T2DM), using evidence from both clinical trial and real-world studies. METHODS: An established T2DM model was adapted to use contemporary outcomes evidence from real-world studies and randomized controlled trial evaluations of SGLT2i, and extrapolated over a lifetime for HHF, myocardial infarction, stroke, end-stage renal disease and all-cause mortality. The economic analysis considered adults with T2DM, with and without established cardiovascular disease, and was conducted over a lifetime from the perspective of the health care payer in the United Kingdom, United States and China, discounted at country-specific rates. RESULTS: SGLT2i were consistently associated with increased treatment costs, reduced complication costs and gains in quality-adjusted life years driven by differences in projected life expectancy, cardiovascular and microvascular morbidity and weight loss. SGLT2i were estimated to be cost-saving or cost-effective at relevant thresholds for the overall population in the United Kingdom, United States and China, with cost-effectiveness being the greatest in higher risk subgroups. CONCLUSIONS: The findings highlight the need to take into account cost savings from reducing common, morbid and preventable T2DM complications when considering the cost of diabetes medications.

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.

Eligibility of patients with type 2 diabetes for sodium-glucose co-transporter-2 inhibitor cardiovascular outcomes trials: An assessment using the Diabetes Collaborative Registry.

Generalizability of findings from cardiovascular outcomes trials (CVOTs) to patients with type 2 diabetes (T2D) in clinical practice is unknown. We assessed the proportions of patients in the Diabetes Collaborative Registry who would have met enrolment criteria for pivotal CVOTs of sodium-glucose co-transporter-2 inhibitors (SGLT-2is): EMPA-REG OUTCOME, CANVAS, DECLARE and VERTIS CV. In 172 643 patients, mean [standard deviation (SD)] age and HbA1c were 68.1 (11.8) years and 7.8% (2.2), respectively; 56.8% of patients were men and SGLT-2i use was 4.4%. Atherosclerotic cardiovascular disease (ASCVD) prevalence was 64.3% and mean 10-year ASCVD risk was 28.6% in patients without ASCVD. Proportions of patients eligible for CVOTs ranged from 26% (EMPA-REG OUTCOME) to 44% (DECLARE); 48% of patients were ineligible for all CVOTs. Mean (SD) ASCVD risk was 25.4% (22.6), 32.1% (20.6) and 37.7% (19.4) in patients eligible for no, one or two CVOTs, respectively. SGLT-2i use was low in patients eligible for no CVOTs (3.5%) and at least one CVOT (5.2%). In conclusion, applicability of CVOT results to patients with T2D in clinical practice varies based on trial eligibility criteria.

Comparison of healthcare resource utilization and costs in patients with type 2 diabetes initiating dapagliflozin versus sitagliptin.

AIMS: To compare healthcare costs and utilization in patients with type 2 diabetes (T2D) who initiated dapagliflozin (DAPA) with costs and utilization in those who initiated sitagliptin (SITA) in a real-world setting. MATERIALS AND METHODS: This was a retrospective study of health plan enrollees in two US commercial claims databases or Medicare Part D. The study population comprised adult patients with T2D who initiated DAPA or SITA between January 1, 2014 and April 30, 2015. DAPA and SITA initiators were propensity-score-matched, and healthcare utilization and costs during the 1-year follow-up period were compared. Analyses were conducted separately for patients with evidence of oral antidiabetic drug (OAD) monotherapy use at baseline. RESULTS: A total of 2722 patients were included in each matched cohort. Follow-up unadjusted all-cause costs ($16 065 and $17 281; P = 0.135) and diabetes-related costs ($9697 and $9354; P = 0.539) were similar in the DAPA and SITA cohorts. Higher office and outpatient visit costs in the SITA group were offset by higher pharmacy costs in the DAPA group. In the subgroup of 1804 patients with OAD monotherapy use at baseline, patients in the SITA group had higher total all-cause costs compared with those in the DAPA group ($14 884 vs. $12 353; P = 0.026). CONCLUSION: Patients who initiated DAPA or SITA had similar all-cause and diabetes-related healthcare costs over 1 year of follow-up. In the subgroup of patients treated with OAD monotherapy at baseline (84% metformin monotherapy), those who initiated DAPA as add-on therapy had lower costs than patients who added SITA.

Impact of opioid-induced constipation on healthcare resource utilization and costs for cancer pain patients receiving continuous opioid therapy.

PURPOSE: Opioid therapy is often associated with adverse effects, including opioid-induced constipation (OIC), in patients receiving opioids for cancer pain. This retrospective observational cohort study evaluated healthcare utilization and costs during the first year after initiating opioid therapy among cancer patients with (cohort 1) and without (cohort 2) constipation. METHODS: This study used administrative claims data from the HealthCore Integrated Research Environment between January 1, 2006, and April 30, 2014. Eligible patients included adults ≥ 18 years with a diagnosis of cancer who initiated continuous opioid therapy (≥ 30 days). Propensity scores were used to match patients with constipation in a 1:1 ratio to those without constipation. Generalized linear models were used to evaluate healthcare utilization and costs during the 12 months after initiating opioid therapy. RESULTS: After matching, 1369 patients were included in each cohort. Patients with constipation were more than twice as likely as those without constipation to have an all-cause inpatient hospitalization (odds ratio [95% confidence interval (CI)], 2.47 [2.11-2.90]), or pain-related hospitalization (2.15 [1.82-2.54]) during the 12 months after initiating therapy. Mean unadjusted overall healthcare costs during the first 12 months post-index were $21,629 (95% CI, $14,850-$29,018) higher for patients with constipation than for those without constipation. For patients with constipation, total mean (SD) constipation-related costs were $9196 ($26,896). CONCLUSIONS: These results suggest that OIC is associated with significantly increased healthcare and economic burden in cancer pain patients and that early and ongoing recognition and management of OIC are unmet needs in this population.

All-cause and diabetes-related healthcare costs among US adults with type 2 diabetes initiating exenatide once weekly or insulin glargine.

AIMS: To compare healthcare utilization and costs between patients with type 2 diabetes (T2D) treated with exenatide (Bydureon) once weekly (EQW) and patients treated with insulin glargine (IG). MATERIALS AND METHODS: Using the MarketScan Commercial and Medicare Supplemental databases, we conducted a retrospective cohort study of adult US patients with claim with a diagnosis of T2D, initiating EQW or IG from February 1, 2012 to June 30, 2014 (first claim = index date). All-cause and diabetes-related utilization and costs were measured during the 12 months after the index date. EQW patients were matched 1:1 to IG patients, using propensity scores. Logistic and ordinary least-squares regression models were fit to model differences between the matched cohorts. RESULTS: There were 7749 EQW patients matched to 7749 IG patients. EQW patients had significantly (P < .05) lower odds of all-cause inpatient (IP) admissions (odds ratio = 0.737 [95% confidence interval, 0.661, 0.822]), diabetes-related IP admissions (0.720 [95% confidence interval, 0.635, 0.815]) and diabetes-related IP admissions or emergency room visits (0.778 [95% confidence interval, 0.713, 0.847]). EQW patients had significantly (P < .05) lower all-cause (cost difference = -113 USD [95% confidence interval, -120 USD, -106 USD]) and diabetes-related (-806 USD [95% confidence interval, -871 USD, -746 USD]) medical costs, and had significantly (P < .05) higher all-cause total costs (ie, medical plus pharmacy) (3228 USD [95% confidence interval, 3110 USD, 3367 USD]), diabetes-related total costs (1951 USD [95% confidence interval, 1873 USD, 2036 USD]), all-cause pharmacy costs (2792 USD [95% confidence interval, 2700 USD, 2928 USD]) and diabetes-related pharmacy costs (1923 USD [95% confidence interval, 1890 USD, 1957 USD]) than those of IG patients. CONCLUSIONS: Among adults with T2D, EQW initiators had lower odds of IP admission and lower medical costs in the 12 months after initiation than IG initiators. Higher total costs in EQW patients were driven by greater pharmacy costs.

Comparative effectiveness of once-weekly glucagon-like peptide-1 receptor agonists with regard to 6-month glycaemic control and weight outcomes in patients with type 2 diabetes.

A retrospective cohort study was conducted in patients with type 2 diabetes in an electronic medical record database to compare real-world, 6-month glycated haemoglobin (HbA1c) and weight outcomes for exenatide once weekly with those for dulaglutide and albiglutide. The study included 2465 patients: exenatide once weekly, n = 2133; dulaglutide, n = 201; and albiglutide, n = 131. The overall mean (standard deviation [s.d.]) age was 60 (11) years and 54% were men; neither differed among the comparison groups. The mean (s.d.) baseline HbA1c was similar in the exenatide once-weekly (8.3 [1.7]%) and dulaglutide groups (8.5 [1.5]%; P = .165), but higher in the albiglutide group (8.7 [1.7]%; P < .001). The overall mean (s.d.) HbA1c change was -0.5 (1.5)% (P < .001) and this did not differ among the comparison groups in either adjusted or unadjusted analyses. The mean (s.d.) weight change was -1.4 (4.7) kg for exenatide once weekly and -1.6 (3.7) kg for albiglutide (P = .579), but was greater for dulaglutide, at -2.7 (5.7) kg (P = .001). Outcomes were similar in subsets of insulin-naive patients with baseline HbA1c ≥7.0% or ≥9.0%. All agents significantly reduced HbA1c at 6 months, with no significant differences among agents or according to baseline HbA1c in insulin-naive subgroups.

Rates of myocardial infarction and stroke in patients initiating treatment with SGLT2-inhibitors versus other glucose-lowering agents in real-world clinical practice: Results from the CVD-REAL study.

The multinational, observational CVD-REAL study recently showed that initiation of sodium-glucose co-transporter-2 inhibitors (SGLT-2i) was associated with significantly lower rates of death and heart failure vs other glucose-lowering drugs (oGLDs). This sub-analysis of the CVD-REAL study sought to determine the association between initiation of SGLT-2i vs oGLDs and rates of myocardial infarction (MI) and stroke. Medical records, claims and national registers from the USA, Sweden, Norway and Denmark were used to identify patients with T2D who newly initiated treatment with SGLT-2i (canagliflozin, dapagliflozin or empagliflozin) or oGLDs. A non-parsimonious propensity score was developed within each country to predict initiation of SGLT-2i, and patients were matched 1:1 in the treatment groups. Pooled hazard ratios (HRs) and 95% CIs were generated using Cox regression models. Overall, 205 160 patients were included. In the intent-to-treat analysis, over 188 551 and 188 678 person-years of follow-up (MI and stroke, respectively), there were 1077 MI and 968 stroke events. Initiation of SGLT-2i vs oGLD was associated with a modestly lower risk of MI and stroke (MI: HR, 0.85; 95%CI, 0.72-1.00; P = .05; Stroke: HR, 0.83; 95% CI, 0.71-0.97; P = .02). These findings complement the results of the cardiovascular outcomes trials, and offer additional reassurance with regard to the cardiovascular effects of SGLT-2i, specifically as it relates to ischaemic events.

Clinical Outcomes in Patients with CKD and Rapid or Non-rapid eGFR Decline: A Report from the DISCOVER CKD Retrospective Cohort.

INTRODUCTION: This analysis examined the baseline characteristics and clinical outcomes of patients with chronic kidney disease (CKD) and rapid or non-rapid estimated glomerular filtration rate (eGFR) decline, using retrospective data from DISCOVER CKD (ClinicalTrials.gov, NCT04034992). METHODS: Data (2008-2020) were extracted from UK Clinical Practice Research Datalink, US TriNetX, US Limited Claims and Electronic Health Record Dataset, and Japan Medical Data Vision. Patients with CKD (two consecutive eGFR measures < 75 mL/min/1.73 m2 recorded 90-730 days apart) were included. Rapid eGFR decline was defined as an annual decline of > 4 mL/min/1.73 m2 at 2 years post-index; non-rapid eGFR decline was defined as an annual decline of ≤ 4 mL/min/1.73 m2. Clinical outcomes assessed included all-cause mortality, kidney outcomes (composite risk of kidney failure [progression to CKD stage 5] or > 50% eGFR decline, and kidney failure alone), cardiovascular events-including major adverse cardiovascular events (MACE; non-fatal myocardial infarction/stroke and cardiovascular death)-and all-cause hospitalization. RESULTS: Across databases, rapid eGFR decline occurred in 13.7% of 804,237 eligible patients. Mean annual eGFR decline ranged between - 6.21 and - 6.86 mL/min/1.73 m2 in patients with rapid eGFR decline versus between - 0.11 and - 0.77 mL/min/1.73 m2 in patients with non-rapid eGFR decline. Rapid eGFR decline was associated with increased comorbidity burden and medication prescriptions. Across databases, the composite risk of kidney failure or > 50% decline in eGFR was significantly greater in patients with rapid versus non-rapid eGFR decline (P < 0.01); all-cause mortality, kidney failure alone, MACE, and all-cause hospitalization each significantly increased in two databases (P < 0.01-0.05). CONCLUSION: Understanding patient factors associated with rapid eGFR decline in patients with CKD may help identify individuals who would benefit from proactive management to minimize the risk of adverse outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04034992.

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.

Prevalence of undiagnosed stage 3 chronic kidney disease in France, Germany, Italy, Japan and the USA: results from the multinational observational REVEAL-CKD study.

OBJECTIVES: REVEAL-CKD aims to estimate the prevalence of, and factors associated with, undiagnosed stage 3 chronic kidney disease (CKD). DESIGN: Multinational, observational study. SETTING: Data from six country-specific electronic medical records and/or insurance claims databases from five countries (France, Germany, Italy, Japan and the USA [two databases]). PARTICIPANTS: Eligible participants (≥18 years old) had ≥2 consecutive estimated glomerular filtration rate (eGFR) measurements (calculated from serum creatinine values, sex and age) taken from 2015 onwards that were indicative of stage 3 CKD (≥30 and <60 mL/min/1.73 m2). Undiagnosed cases lacked an International Classification of Diseases 9/10 diagnosis code for CKD (any stage) any time before, and up to 6 months after, the second qualifying eGFR measurement (study index). MAIN OUTCOME MEASURES: The primary outcome was point prevalence of undiagnosed stage 3 CKD. Time to diagnosis was assessed using the Kaplan-Meier approach. Factors associated with lacking a CKD diagnosis and risk of diagnostic delay were assessed using logistic regression adjusted for baseline covariates. RESULTS: The prevalence of undiagnosed stage 3 CKD was 95.5% (19 120/20 012 patients) in France, 84.3% (22 557/26 767) in Germany, 77.0% (50 547/65 676) in Italy, 92.1% (83 693/90 902) in Japan, 61.6% (13 845/22 470) in the US Explorys Linked Claims and Electronic Medical Records Data database and 64.3% (161 254/250 879) in the US TriNetX database. The prevalence of undiagnosed CKD increased with age. Factors associated with undiagnosed CKD were female sex (vs male, range of odds ratios across countries: 1.29-1.77), stage 3a CKD (vs 3b, 1.81-3.66), no medical history (vs a history) of diabetes (1.26-2.77) or hypertension (1.35-1.78). CONCLUSIONS: There are substantial opportunities to improve stage 3 CKD diagnosis, particularly in female patients and older patients. The low diagnosis rates in patients with comorbidities that put them at risk of disease progression and complications require attention. TRIAL REGISTRATION: NCT04847531.

Understanding Patient Perspectives of the Impact of Anemia in Chronic Kidney Disease: A United States Patient Survey.

Anemia in chronic kidney disease (CKD) is associated with reduced health-related quality of life and physical functioning. This study investigated knowledge and awareness of anemia in patients with CKD in the United States (US) through an online, quantitative survey administered to patients aged ≥18 years with self-reported CKD, with or without anemia. Of 446 patients included, 255 (57.2%) were diagnosed with anemia and 191 (42.8%) were in the non-anemia cohort. In patients with anemia, 71.0% were aware of the relationship between CKD and anemia versus 52.9% in the non-anemia cohort. In the anemia cohort, 46.3% of patients were aware of their hemoglobin level, versus 27.2% in the non-anemia cohort. Despite 67.4% of patients with anemia believing their condition was well/very well managed, only 50% reported being informed about different treatments without prompting healthcare providers. In the US, patients with anemia and CKD perceived that anemia had a negative impact on physical health and emotional wellbeing. Results emphasize a lack of disease awareness, suggesting patients would benefit from further education on anemia in CKD.

Contemporary outcomes of anemia in US patients with chronic kidney disease.

BACKGROUND: Long-term clinical outcome data from patients with non-dialysis-dependent (NDD) chronic kidney disease (CKD) are lacking. We characterized patients with NDD-CKD and anemia using real-world data from the USA. METHODS: This retrospective longitudinal observational study evaluated integrated Limited Claims and Electronic Health Record Data (IBM Health, Armonk, NY), including patients ≥18 years with two or more estimated glomerular filtration rate (eGFR) measures <60 mL/min/1.73 m2 ≥90 days apart. Anemia was defined as the first observed hemoglobin <10 g/dL within 6-month pre- and post-CKD index date. Data were analyzed from January 2012 to June 2018. Patients with documented iron-deficiency anemia at baseline were excluded. RESULTS: Comprising 22 720 patients (57.4% female, 63.9% CKD stage 3, median hemoglobin 12.5 g/dL), median (interquartile range) follow-up for patients with and without anemia were 2.9 (1.5-4.4) and 3.8 (2.2-4.8) years, respectively. The most prevalent comorbidities were dyslipidemia (57.6%), type 2 diabetes mellitus (38.8%) and uncontrolled hypertension (20.0%). Overall, 23.3% of patients had anemia, of whom 1.9% and <0.1% received erythropoiesis-stimulating agents (ESAs) or intravenous iron, respectively. Anemia prevalence increased with CKD stage from 18.2% (stage 3a) to 72.8% (stage 5). Patients with anemia had a higher incidence rate of hospitalizations for heart failure (1.6 versus 0.8 per 100 patient-years), CKD stage advancement (43.5 versus 27.5 per 100 patient-years), and a 40% eGFR decrease (18.1 versus 7.3 per 100 patient-years) versus those without anemia. CONCLUSIONS: Anemia, frequently observed in NDD-CKD and associated with adverse clinical outcomes, is rarely treated with ESAs and intravenous iron. These data suggest that opportunities exist for improved anemia management in patients with NDD-CKD.

Investigating the global prevalence and consequences of undiagnosed stage 3 chronic kidney disease: methods and rationale for the REVEAL-CKD study.

Background: Timely diagnosis and treatment of stage 3 chronic kidney disease (CKD) can prevent further loss of kidney function and progression to kidney failure. However, contemporary data on the global prevalence of undiagnosed stage 3 CKD are scarce. REVEAL-CKD is a multinational, multifocal and observational study aiming to provide insights into undiagnosed stage 3 CKD in a large population. Methods: Patients (aged ≥18 years) with data in selected secondary databases from 11 countries will be included if they have at least two estimated glomerular filtration rate (eGFR) measurements from 2015 onwards that are ≥30 and <60 mL/min/1.73 m2, recorded >90 and ≤730 days apart. Undiagnosed cases are those without an International Classification of Diseases 9/10 diagnosis code for CKD (any stage) any time before and up to 6 months after the second qualifying eGFR measurement. Time to diagnosis will be assessed using a Kaplan-Meier approach; patient characteristics associated with undiagnosed CKD will be assessed using adjusted logistical regression analyses. Results: REVEAL-CKD will assess the point prevalence of undiagnosed stage 3 CKD and time to CKD diagnosis in initially undiagnosed cases overall and in individual countries. Trends in undiagnosed CKD prevalence by calendar year will be assessed. Patient characteristics, healthcare resource utilization, adverse clinical outcomes, and CKD management and monitoring practices in patients with versus without a CKD diagnosis will be compared. Conclusions: REVEAL-CKD will increase awareness of the global clinical and economic burden of undiagnosed stage 3 CKD and provide valuable insights to inform clinical practice and policy changes.

Lifetime cost-effectiveness simulation of once-weekly exenatide in type 2 diabetes: A cost-utility analysis based on the EXSCEL trial.

AIMS: The Exenatide Study of Cardiovascular Event Lowering (EXSCEL) trial assessed once-weekly exenatide (EQW) vs. placebo, added to usual care in 14,752 patients with type 2 diabetes mellitus (Clinicaltrials.gov: NCT01144338). We assessed the lifetime cost-effectiveness of adding EQW vs. usual care alone from a healthcare perspective. METHODS: Medical resource use and EQ-5D utilities were collected throughout the study. Within-trial results were extrapolated to a lifetime horizon using the UK Prospective Diabetes Study Outcomes Model version 2 (UKPDS-OM2), predicting predict cardiovascular and microvascular events. Cost-effectiveness was evaluated separately for US and UK settings, with outcomes measured in quality-adjusted life-years (QALYs). RESULTS: EQW plus usual care gained 0.162 QALYs at an additional cost of $41,545/patient, compared with usual care in a US setting. The incremental cost-effectiveness ratio (ICER) was $259,223/QALY. In a UK setting, the QALY gain was 0.151 at an additional cost of £6357: an ICER of £42,589/QALY. Sensitivity analyses ranged between $34,369-$269,571 and £3430-£46,560 per QALY gained. CONCLUSIONS: In a lifetime extrapolation, adding EQW to usual care increased QALYs and costs compared with usual care alone. The base-case ICERs exceeded the commonly-cited cost-effectiveness thresholds of $100,000/QALY and £20,000/QALY. However, ICERs were considerably lower in some subgroups, and in sensitivity analyses.