Vifor Pharma Research Articles

Impact of a bundle of care (intravenous iron, erythropoietin and transfusion metabolic adjustment) on post-operative transfusion incidence in cardiac surgery: a single-centre, randomised, open-label, parallel-group controlled pilot trial

Red blood cell (RBC) transfusions are frequent in patients after cardiac surgery. This study assessed whether a bundle of care including pre-operative and post-operative administration of erythropoietin (EPO) with intravenous iron supplementation, and restrictive transfusion adjusted for ScvO2 could result in reduced postoperative transfusions. In this single-centre, randomised, open-label, parallel-group controlled pilot study, patients undergoing elective cardiac surgery with high risk of transfusion in a University Hospital were enrolled by the investigator and the randomisation procedure using a central internet-based system was made by the clinical research assistant. Since the trial was open-label, no masking was used. Patients were assigned (1:1) to either the STOP group (40,000 IU subcutaneous EPO combined with 20mg/kg intravenous ferric carboxymaltose if Hb<13g/dL the day before surgery or at ICU admission, and RBC transfusion if Hb≤8g/dL and ScvO2≤65%, or additional EPO dose if 8<Hb<13g/dL) or to the control group (RBC transfusion if Hb≤8g/dL, or, if 8<Hb<13g/dL, intravenous iron sucrose 200mg or 300mg according to weight). Primary outcome was the incidence of postoperative RBC transfusion up to hospital discharge or postoperative day 28. The trial is registered with ClinicalTrials.gov, NCT04141631. Between Jan 20, 2020, and Sept 6, 2022, among 128 patients enrolled, 123 (male, 54.4%, 67/123) were included in the full analysis set: 62 in the STOP group and 61 in the control group. Nine patients (14.5%, 9/62) in the STOP group required RBC transfusion vs 19 (31.2%, 19/61) in the control group (odds ratio 0.37 [95% CI: 0.15-0.91], p=0.03). The median length of follow up to transfusion was 2.6 days (1.5; 4.6) and 3.3 (1.6; 4.2) in control and STOP groups respectively (p=0.61). The bundle of care may reduce postoperative RBC transfusion. The findings should be taken with caution due to the unblinded and exploratory nature of the study. University of Montpellier Hospital and Vifor Pharma.

P041 Health-related quality of life in patients receiving glucocorticoids for a rheumatic disease and associated factors : a cross-sectional study

Abstract Background/Aims Glucocorticoids (GCs) used in the treatment of inflammatory rheumatic conditions can impact on patients in different ways. The objective of this study was to identify socio-demographic and clinical factors associated with health-related quality of life (HRQoL) in patients undertaking GCs for a rheumatic disease. Methods This was a cross-sectional study using online survey methods. Participants taking GCs for a rheumatic disease from Australia, United Kingdom and the United States of America were included. HRQoL was measured using the EQ-5D-5L converted into a linear EQ5D index value. Eight explanatory factors (age, sex, country, educational level, employment status, disease group, self-reported disease state, and dose of GCs) were tested for potential association with HRQoL using univariable and multivariable (hierarchical) analyses. Factors found to have a significant association with EQ5D index at a P &amp;lt; 0.05 level in the multivariable model were considered to be independently associated with HRQoL. Results A total of 945 patients completed the EQ-5D-5L with no missing values: UK n = 742 (79%); USA n = 139 (15%); Australia/New Zealand n = 64 (7%); mean age 57.6 (SD = 13.6); 833 (88%) women. Participants with inflammatory arthritis n = 197 (21%), connective tissue disease and/or vasculitis n = 402 (43%), giant cell arteritis and/or polymyalgia rheumatica n = 346 (37%) were included. Those with self-reported active disease were 726 (77%). Mean (SD) EQ5D index was 0.64 (0.25); there were significant differences between groups in EQ-5D-5L index by age (median split, t=-3.77, p &amp;lt; 0.001); sex (t = 3.40, p &amp;lt; 001); educational level (F[3]=10.51, p &amp;lt; 0.001); employment status (F[6]=37.67, P &amp;lt; 0.001); disease group (T[2]=20.23, p &amp;lt; 0.001); disease state (T=-8.46, p &amp;lt; 0.001); and the dose of GCs(T = 2.95, p &amp;lt; 0.001). Worse HRQoL was associated with older age, being female, low educational attainment, being unemployed, having an inflammatory arthritis or a CTD, disease being active, and taking a higher dose of GC. Of the eight factors that were tested in the multivariable model, five were found to be independently associated with HRQoL. These were: disease state (β = 0.12, p &amp;lt; 0.001), disease group (β = 0.06, p &amp;lt; 0.001), employment status (β = 0.05, p &amp;lt; 0.001), sex (β = 0.05, p &amp;lt; 0.001), and educational level (β = 0.04, p &amp;lt; 0.001). This 5-factor model explained 18% of the variance in EQ5D index scores (F[1, 926] = 4.97, P = 0.026). The excluded factors in the model were age, dose, and country. Conclusion In our data, we identified 5 factors independently associated with worse HRQoL in patients being treated with GCs. Over 80% of the variance was not explained by our model likely due to use of a generic HRQoL measure (EQ-5D-5L) as outcome variable, and the small number of explanatory variables tested within this survey. Further research is required to identify potential targets to support interventions. Disclosure S. Janagan: None. K. Lim: None. R. Bhogal: None. S. Bridgewater: Grants/research support; Vifor pharma. C. Silverthorne: None. P. Richards: None. J. Dawson: None. E. Dures: Grants/research support; Vifor pharma. C. Hill: None. S. Goodman: Consultancies; UCB. Grants/research support; Novartis. S.L. Mackie: Consultancies; Consultancy on behalf of her institution for Roche/Chugai, Sanofi, AbbVie, AstraZeneca, Pfizer. Other; Investigator on clinical trials for Sanofi, GSK, Sparrow, speaking/lecturing on behalf of her institution for Roche/Chugai, Vifor, Pfizer, UCB, Novartis and AbbVie, ; chief investigator on STERLING-PMR trial, funded by NIHR; patron of the charity PMRGCAuk, No personal remuneration was received for any of the above activities. Support from Roche/Chugai to attend EULAR2019 in person and from Pfizer to attend ACR Convergence 2021 virtually., SLM is supported in part by the NIHR Leeds Biomedical Research Centre., The views expressed in this article are those of the authors and not necessarily those of the NIHR,the NIHR Leeds Biomedical Research Centre, the National Health Service or the UK Department of Health. M. Ndosi: Grants/research support; Vifor pharma. J.C. Robson: Consultancies; Vifor Pharma. Member of speakers’ bureau; Vifor Pharma. Grants/research support; Unrestricted Grant/research support from: Vifor Pharma.

P186 Impact of glucocorticoids on appearance and sense of self in rheumatic diseases

Abstract Background/Aims To explore patients’ perspectives on the impact of appearance changes attributed to glucocorticoid treatment. Methods We conducted a secondary analysis of semi-structured interviews with patients with rheumatic conditions receiving glucocorticoids in the UK, USA, and Australia. Interview data were analysed inductively to develop preliminary individual and overarching themes. Results 60 patient interviews were analysed. Patients ranged from 26-84 years, and 39 (65%) were female. Patients had diagnoses of systemic vasculitis (n = 19), inflammatory arthritis (n = 14), crystal arthropathy (n = 2), connective tissue disorders (n = 16), or other/multiple (n = 9). Interviews contained rich data on how appearance changes impacted health-related quality of life. Three preliminary overarching themes were identified. i) Societal influences: participants reported pressure to conform to cultural and societal ideals: “I think with the weight gain it was more of an emotional response. [⋯] There's a part of you that's thin is better. So, I think that impacted me the most, just because of that aspect of what others thought of me…” (Female [Mixed/Multiple ethnicity] aged 27, granulomatosis with polyangiitis [Australia]) and “…within a week my dad had seen me and said, “Gosh you’ve put on a lot of weight”. Obviously, that’s not what I want to hear [⋯] but I think it was just pure shock." (White female aged 40, eosinophilic granulomatosis with polyangiitis [UK])”.ii)?Impact on mental health and sense of self: glucocorticoids were often described as making participants ‘not look like’ themselves, associated with changes in mood, self-confidence, and reluctance to socialise: “It makes you feel down. It makes you feel depressed. You don't want to socialise because you're not you.” (White male aged 65, inflammatory myositis [Australia]) and “Yeah, that’s it and it will hopefully look nice, which is a really vain thing to think about isn’t it, but it does really affect [⋯] how you feel and kind of your state of mind and things…” (White female aged 39, Takayasu arteritis [UK]). iii) Burden of adjustments included dieting, purchasing additional clothing sizes, working from home, discontinuing hobbies, and postponing key life events: "I have a wardrobe right now that goes four different sizes as my weight goes up and down and up and down." (White female aged 55, systemic lupus erythematosus [USA]) and "Well, with the high dose of prednisone since I gained weight, I get really tired if I try to do like exercise or something. And I used to be very sporty, so that just completely changed." (Hispanic female aged 29, systemic lupus erythematosus [USA]). Conclusion Patients attribute a variety of impacts on their health-related quality of life to glucocorticoid-related appearance changes and report a burden of adjustments above management of their chronic rheumatic condition. Further work is required to establish ways to mitigate these through improved information provision and support. Disclosure S.J. Lax: Grants/research support; post funded by National Institute for Health and Care Research Advanced Fellowship [grant number NIHR300863]. E. Dures: Grants/research support; recipient of grants from Above &amp; Beyond Bristol Hospitals Charity, UWE Bristol, Vifor Pharma, National Institute for Health and Care Research (Research for Patient Benefit) and Sanofi. S. Bridgewater: None. C. Silverthorne: None. V. Lowndes: None. P. Richards: None. J. Dawson: None. C. Hill: Grants/research support; recipient of an Australian Rheumatology Association Project Grant, administered by Arthritis Australia. S. Goodman: None. S.L. Mackie: None. M.E. Ndosi: None. F.A. Pearce: Grants/research support; recipient of a National Institute for Health and Care Research Advanced Fellowship [grant number NIHR300863] and a grant from Vifor pharma. J. Robson: Consultancies; consultancy and speaking fees from Vifor Pharma. Grants/research support; recipient of grants from Above &amp; Beyond Bristol Hospitals Charity, UWE Bristol, Vifor Pharma, National Institute for Health and Care Research (Research for Patient Benefit) and Sanofi.

OA06 Regional differences in work productivity in patients with early rheumatoid arthritis in England and Wales

Abstract Background/Aims Inflammatory arthritis including rheumatoid arthritis (RA) causes significant work disability. Rapid diagnosis and early intervention can reduce the impact of disease. We have previously shown significant regional variation in care delivery. In this study we aim to study regional variation in work outcomes in early RA in England and Wales. Methods We used data from the UK National Early Inflammatory Arthritis Audit between April 2018 and March 2023 to identify patients with early-onset RA in England and Wales. At diagnosis, clinicians collected information on demographics and disease activity. Participants were invited to complete work outcome questionnaires at baseline and 3 months. Our analysis was restricted to patients with work data available at 3 months. The primary outcome was discontinuation of work due to arthritis. Patient characteristics were tabulated by region. Regression models (adjusted for age and gender) examined the associations between work discontinuation and region. Clustered standard errors were estimated to account for within-Trust correlations. Sensitivity models further explored the effects of deprivation and treatment delay. Results A total of 3,730 patients with confirmed RA provided work data. Mean age was 67, 62.3% were female and 7.8% from minority ethnic backgrounds. 14% were current smokers and 55.6% had one or more comorbidities. Median baseline DAS28 was 5.2 (IQR: 4.2-6.1). 363/3730 (10%) had stopped work due to RA by 3 months. 534/3,730 (14%) stopped work for any reason. In regression analysis, significant regional differences were seen in the odds of stopping work due to RA. The Midlands was the largest regional contributor of data and was used as the reference group. Patients from Northwest England were most likely to stop work by 3 months (age- and gender-adjusted OR 1.59, [95% CI 1.13-2.25]) with Midlands patients least likely. Sensitivity analysis showed that deprivation and treatment delay only partially attenuate the association between region and work outcome (OR for Northwest 1.57 [1.06-2.33]). Conclusion There is evidence of regional variation in the impact of new onset RA on work participation. Our analyses suggest that the associations are only partly explained by regional differences in care delivery or deprivation. Other factors such as job type and access to occupational health support warrant further investigation. Disclosure E. Alveyn: Other; Educational support from UCB. M. Adas: None. I. Sahbudin: None. A. Boonen: None. K. Bechman: Honoraria; UCB, Vifor Pharma. M.D. Russell: Honoraria; Abbvie, BioGen, Lilly, Galapagos, Menarini. Other; Educational grants from Lilly, Janssen, Pfizer, UCB. D. Nagra: Honoraria; Abbvie, Galapagos, Lilly. Other; Educational support from UCB. S. Gallagher: None. E. Price: None. K. Walker-Bone: None. S. Norton: None. J. Galloway: Honoraria; AbbVie, Celgene, Chugai, Gilead, Janssen, Eli Lilly, Pfizer, Roche and UCB.

An evaluation of sexual function and health-related quality of life following laparoscopic surgery in individuals living with endometriosis.

What is the relationship between sexual function, health-related quality of life (HRQoL), and laparoscopic surgery in individuals living with endometriosis? A higher number of laparoscopic surgeries is significantly associated with poorer HRQoL and greater levels of sexual dysfunction in individuals with endometriosis. Prior research indicates that endometriosis is associated with lowered HRQoL and sexual function and that these outcomes are influenced by endometriosis-related symptom profiles, medical, and surgical management. A limited number of studies have examined changes in sexual function in individuals with endometriosis following laparoscopic surgery or following repeated surgeries. A cross-sectional community-based online survey was used to examine the relationships between sexual function, HRQoL, and laparoscopic surgery (n = 210). Individuals with a self-reported diagnosis of endometriosis were recruited via online advertising through social media and gynaecology clinics. Endometriosis-specific data (e.g. diagnostic delay, symptom experience) was collected in addition to engagement with laparoscopic surgery, level of HRQoL (EuroQol-5 Dimension: EQ-5D-5L), and sexual function (Female Sexual Function Index: FSFI). Bivariate correlational analyses and hierarchical multiple regression were used to determine the associations between the variables of interest. Individuals with endometriosis have substantially poorer HRQoL in comparison to Australian normative samples, with greater levels of endometriosis-related symptom burden, distress, and pain significantly associated with lower levels of HRQoL. The mean FSFI score was suggestive of clinically significant female sexual dysfunction, with the lowest level of function noted in the domain of sexual pain and the highest level of function noted in the sexual satisfaction domain. A greater number of laparoscopic surgeries was significantly associated with poorer overall HRQoL and greater levels of sexual dysfunction. The cross-sectional nature of the data precludes direct findings of causality and further longitudinal research is recommended. The information pertaining to engagement in laparoscopic surgery was self-report in nature and was not medically verified. The study's findings highlight the pervasive impact of endometriosis on all domains of living, emphasizing the need to extend treatment planning beyond that of physical pain management alone. Early referral for assessment and management of sexual wellbeing is recommended prior to, and post-surgical intervention, with a focus on maintaining post-surgical changes, potentially reducing the need for multiple surgeries. The study was not associated with research funding. Author CN reports grant funding from the Australian Government and Medical Research Future Fund (MRFF) and was a previous employee of CSL Vifor (formerly Vifor Pharma Pty Ltd). N/A.

407-P: Efficacy of Finerenone in Patients with Abnormal Markers of Liver Steatosis and Fibrosis—A FIDELITY Subgroup Analysis

Introduction: Finerenone, a selective, nonsteroidal mineralocorticoid receptor antagonist, showed cardiorenal benefits vs placebo in patients with chronic kidney disease and type 2 diabetes. Here, we analyzed patients with liver function abnormalities in FIDELITY, a prespecified pooled dataset from the FIDELIO-DKD and FIGARO-DKD trials. Methods: Patients with urine albumin-to-creatinine ratio ≥30-≤5000 mg/g and estimated glomerular filtration rate (eGFR) ≥25 mL/min/1.73 m2 and type 2 diabetes were analyzed according to elevated transaminases, high risk of steatosis (hepatic steatosis index [HSI] &amp;gt;36), and risk of intermediate to advanced fibrosis (Fibrosis-4 Index [FIB-4] scores &amp;gt;1.30, &amp;gt;2.67, and &amp;gt;3.25). Changes in liver function and in kidney (kidney failure, sustained 57% eGFR decline, or renal death) and cardiovascular (CV; CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) composite outcomes were assessed. Results: Across 13,026 patients, finerenone reduced the risk of kidney and CV outcomes compared with placebo in patients with elevated transaminases (HR=0.75; 95% CI 0.50-1.13 and HR=0.81; 95% CI 0.62-1.07, respectively), at high risk of steatosis (HR=0.75; 95% CI 0.64-0.88 and HR=0.85; 95% CI 0.77-0.95, respectively), and at high risk of intermediate fibrosis (HR=0.75; 95% CI 0.60-0.93 and HR=0.76; 95% CI 0.67-0.87, respectively), with stronger reductions in the risk of the CV composite outcome at higher FIB-4 scores (HR=0.61; 95% CI 0.41-0.92; p-value for interaction=0.13 and HR=0.48; 95% CI 0.25-0.90; p-value for interaction=0.03 for FIB-4 &amp;gt;2.67 and &amp;gt;3.25, respectively). Liver transaminase levels remained consistent between treatment groups throughout the study. Conclusions: Finerenone demonstrated robust and consistent cardiorenal benefits in patients with abnormal liver function and even more profound CV benefits in patients with higher FIB-4 scores. Disclosure N.Perakakis: Advisory Panel; Bayer Inc., Other Relationship; Novo Nordisk, Novo Nordisk. P.Kolkhof: Employee; BAYER AG. R.Lawatscheck: Employee; Bayer Inc. C.Scott: None. G.Bakris: Advisory Panel; Janssen Pharmaceuticals, Inc., Consultant; AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Other Relationship; Bayer Inc. S.R.Bornstein: None. A.L.Birkenfeld: None. A.Linkermann: None. S.Anker: Advisory Panel; AstraZeneca, Novartis AG, Consultant; Bayer Inc., Boehringer Ingelheim Pharma GmbH&amp;Co.KG, Vifor Pharma Management Ltd., Research Support; Abbott, Vifor Pharma Management Ltd. G.Filippatos: Other Relationship; Boehringer-Ingelheim, Bayer Inc., Amgen Inc., Medtronic, Vifor Pharma Management Ltd., Novartis, Servier Laboratories. B.Pitt: Consultant; Bayer Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Vifor Pharma Management Ltd., Lexicon Pharmaceuticals, Inc., PhaseBio Pharmaceuticals, Inc., KBP Bioscience, Merck &amp; Co., Inc. P.Rossing: Other Relationship; Abbott Diagnostics, AstraZeneca, Bayer Inc., Boehringer Ingelheim Inc., Novo Nordisk, Merck KGaA, Gilead Sciences, Inc., Sanofi. L.M.Ruilope: Advisory Panel; Bayer Inc.

829-P: Outcomes with Finerenone in People with CKD and T2D by Baseline Insulin Resistance—A FIDELITY Subgroup Analysis

Introduction Insulin resistance (IR) is associated with increased risk of T2D, CV disease and CKD. Finerenone, a nonsteroidal mineralocorticoid receptor antagonist, has shown cardiorenal benefits in people with CKD and T2D. We investigated if IR is associated with risk of cardiorenal outcomes and if IR modifies finerenone efficacy in the pooled FIDELITY dataset. Methods People with T2D and CKD (UACR ≥30-&amp;lt;300 mg/g + eGFR ≥25-≤90 mL/min/1.73 m2 or UACR ≥300-≤5000 mg/g + eGFR ≥25 mL/min/1.73 m2) and optimized RAS blockade were randomized to finerenone or placebo. Estimated glucose disposal rate (eGDR), an inverse marker of IR, was calculated by 21.158 + (-0.09 × waist circumference [cm]) + (-3.407 × presence of hypertension) + (-0.551 × HbA1c [%]). Risk of CV (time to CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) and kidney (time to kidney failure, sustained ≥57% eGFR decline, or renal death) composite outcomes, and safety, were assessed by eGDR. Results Median baseline eGDR was 4.1 mg/kg/min in 12,964 participants. Analysis by continuous baseline eGDR showed a significantly lower risk of CV events at 3.5 years with increasing eGDR (HR 0.88 [95% CI 0.86-0.91] p&amp;lt;0.01); whereas eGDR was not associated with kidney outcomes. Analyses by eGDR subgroups showed no significant heterogeneity for the effect of finerenone on CV (eGDR &amp;lt;median: HR 0.82 [95% CI 0.72-0.92]; eGDR ≥median: HR 0.91 [95% CI 0.78-1.06]; p-interaction=0.29) or kidney outcomes (eGDR &amp;lt;median: HR 0.85 [95% CI 0.70-1.04]; eGDR ≥median: HR 0.69 [95% CI 0.57-0.84]; p-interaction=0.18). Consistent strength and direction of the associations were observed across sensitivity analyses. Adverse events were similar across eGDR subgroups; hyperkalaemia events were higher with finerenone than placebo. Conclusions A higher risk of CV, but not kidney, outcomes was observed with greater IR in people with T2D and CKD. Finerenone efficacy and safety were not modified by baseline IR. Disclosure T.Ebert: Advisory Panel; Sanofi, Bayer Inc., Research Support; AstraZeneca, Speaker's Bureau; CME-Verlag, Santis, Fresenius Medical Care. K.Rohwedder: Employee; Bayer Inc., AstraZeneca. P.Rossing: Other Relationship; Abbott Diagnostics, AstraZeneca, Bayer Inc., Boehringer Ingelheim Inc., Novo Nordisk, Merck KGaA, Gilead Sciences, Inc., Sanofi. S.Anker: Advisory Panel; AstraZeneca, Novartis AG, Consultant; Bayer Inc., Boehringer Ingelheim Pharma GmbH&amp;Co.KG, Vifor Pharma Management Ltd., Research Support; Abbott, Vifor Pharma Management Ltd. L.M.Ruilope: Advisory Panel; Bayer Inc. P.Fioretto: Advisory Panel; Eli Lilly and Company, Novo Nordisk, Speaker's Bureau; AstraZeneca, Boehringer-Ingelheim, Bayer Inc. V.Fonseca: Consultant; Abbott, Corcept Therapeutics, Eli Lilly and Company, Other Relationship; BRAVO4HEALTH, LLC, Research Support; Fractyl Health, Inc., Stock/Shareholder; Amgen Inc. G.Umpierrez: Research Support; Abbott, Dexcom, Inc., Baxter. A.L.Birkenfeld: None. R.Lawatscheck: Employee; Bayer Inc. C.Scott: None.

272-OR: The Efficacy of Sotagliflozin on Heart-Failure Related Outcomes Is Independent of Baseline A1C

Background: SGLT inhibitors reduce the risk of cardiovascular (CV) events in patients with heart failure (HF) and chronic kidney disease regardless of diabetes status. Although the SOLOIST-WHF and SCORED trials enrolled high CV risk patients with T2DM, participants had a wide range of baseline A1C values. Thus, the present analysis evaluated the effects of sotagliflozin relative to placebo on cardiovascular (CV) death and total HF-related outcomes by baseline A1C range. Methods: SOLOIST-WHF had no baseline A1C entry criteria (baseline median = 7.1%, range = 4.5, 15.0%), while SCORED randomized patients with T2DM and an A1C ≥7% at screening (8.3%, 6.5, 17.3%). Natural cubic splines from Poisson regression models estimated the relationships between continuous A1C and the primary endpoint for both studies: total number of CV deaths, hospitalizations for HF, and urgent visits for HF. Results: Within each trial, patients with higher baseline A1C experienced higher event rates (spline effect p=0.0349 and 0.0014 for SOLOIST-WHF and SCORED, respectively). Sotagliflozin reduced the primary outcome in each trial (p for treatment &amp;lt;0.0001 for both SOLOIST-WHF and SCORED) and this did not differ across A1C (p for interaction &amp;gt;0.10; Figure). Conclusion: Sotagliflozin was effective in reducing the risk of CV death and HF-related events independent of baseline A1C. Disclosure R.Aggarwal: None. D.L.Bhatt: Board Member; Bristol-Myers Squibb Company, Research Support; Lexicon Pharmaceuticals, Inc., Sanofi, Lilly, Boehringer Ingelheim Inc., AstraZeneca, Novo Nordisk. M.Szarek: Consultant; Amarin Corporation, ESPERION Therapeutics, Inc., Other Relationship; Janssen Pharmaceuticals, Inc., Research Support; Lexicon Pharmaceuticals, Inc., Regeneron, Sanofi, Bayer Inc. M.J.Davies: Employee; Lexicon Pharmaceuticals, Inc. P.L.Banks: Employee; Lexicon Pharmaceuticals, Inc. B.Pitt: Consultant; Bayer Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Vifor Pharma Management Ltd., Lexicon Pharmaceuticals, Inc., PhaseBio Pharmaceuticals, Inc., KBP Bioscience, Merck &amp; Co., Inc. P.G.Steg: Advisory Panel; Merck &amp; Co., Inc., Consultant; Sanofi, Amarin Corporation, Amgen Inc., BMS, PhaseBio Pharmaceuticals, Inc., Idorsia Pharmaceuticals Ltd., Novartis AG, Janssen Pharmaceuticals, Inc., AstraZeneca, Research Support; Lexicon Pharmaceuticals, Inc.

884-P: Decentralized N=1 Study—A Feasible Approach to Evaluate Individual Therapy Response to Dapagliflozin

Background: The SGLT2 inhibitor dapagliflozin reduces kidney function decline and urine albumin:creatinine ratio (UACR) on a population level. However, there is marked heterogeneity in the efficacy among individual patients. We conducted a decentralized (i.e. at home) N=1 trial to assess the effect of dapagliflozin in individual patients and the feasibility of remote data collection. Methods: Twenty patients with type 2 diabetes, UACR &amp;gt;20 mg/g and eGFR &amp;gt;30 mL/min/1.73m2 entered the randomized placebo-controlled double-blind N=1 trial. Patients were randomly assigned to two periods of 1-week treatment with dapagliflozin 10 mg/day and two periods of 1-week treatment with placebo in random order with 1-week wash-out periods in between. Patients collected and sent their own data with automatic uploading to an online platform and sent early morning urines 5 times/week to the laboratory for albumin and creatinine assessment. Primary outcome was UACR change from baseline (mixed effects model). The study had 80% power to detect a correlation in UACR change between first and second dapagliflozin period of 0.6. Results: Patients had a mean eGFR of 70.2 mL/min/1.73m2 and median UACR of 94.7 mg/g. During the study, dapagliflozin compared to placebo reduced albuminuria by 15.1% (95%CI 3.3 - 28.2; p=0.013). There was a marked variation in the change from baseline in UACR during dapagliflozin treatment periods (range first and second exposure -26.9 to -4.7% and -30.5 to -5.8%, respectively). The individual change in UACR during the first and second exposure correlated in the dapagliflozin periods (r=0.50; p=0.026) but not in the placebo periods (r=0.09; p=0.69). Of all scheduled urine collections (N=816), only 5 collections (0.61%) were not delivered in the laboratory. Conclusion: The individual UACR response to dapagliflozin varies among individual patients and is consistent upon re-exposure. Remote data collection was very reliable with nearly any missed urine collection. Disclosure J.Beernink: None. G.D.Laverman: Advisory Panel; AstraZeneca, Vifor Pharma Management Ltd., Boehringer Ingelheim Inc., Astellas Pharma Inc., Lilly, Other Relationship; Sanofi, AstraZeneca. H.L.Heerspink: Consultant; AstraZeneca, Boehringer Ingelheim International GmbH, Bayer Inc., Eli Lilly and Company, Chinook Therapeutics Inc., CSL Behring, Gilead Sciences, Inc., George Clinical, Merck &amp; Co., Inc., Janssen Research &amp; Development, LLC, Traveere Pharmaceuticals, Novo Nordisk. N.Jongs: Speaker's Bureau; AstraZeneca.

411-P: Extended Validation of KidneyIntelXTM in Diabetic Kidney Disease

We have previously shown that plasma TNFR1, TNFR2, and KIM-1 combined with clinical variables provides effective risk stratification for kidney outcomes in individuals with diabetic kidney disease (DKD) stages 1-3. With the recommended use of a race-free eGFR and a refinement of our progression endpoint, we sought to develop and independently validate a version 2.0 of KidneyIntelX assay in a previously untested, independent, contemporary cohort of subjects from BioMe Biobank (Mount Sinai Health System, NYC, NY). The primary outcome was a composite of ≥40% sustained decline in eGFR or kidney failure (sustained eGFR&amp;lt;15 ml/min/1.73 m2) within 5 years from enrollment. In a training cohort of 573 patients with DKD from the Penn Medicine Biobank (PMBB), 15.4% experienced the progressive decline in kidney function over a median of 3.1 years. The following features were selected in a training model utilizing optimized random forests to predict the kidney outcome: TNFR1, TNFR2, KIM-1, baseline UACR, HbA1c, and blood urea nitrogen. The external validation cohort (BioMe, n=657) had an 11.7% event rate over a median of 3.8 years. Based on risk categorization cutoffs derived from training, 57%, 35% and 8.3% of participants were classified as low, intermediate and high-risk, respectively. The cumulative event incidence probability in the low, intermediate, and high-risk groups were 5.9% (95% CI: 3.6-9.4%), 21.2% (95% CI: 15.6-28.3%) and 66.9% (95% CI:, 49.3-83.5%). The unadjusted HRs for high vs. low and intermediate vs. low were 18.4 (95% CI: 9.4 -34.6) and 4.2 (95% CI: 2.4-7.4), respectively. After adjustment for age, sex, race, baseline eGFR, uACR, SBP, and HbA1c, the adjusted HRs were 7.7 (95% CI: 3.0-19.6) and 3.7 (95% CI: 2.0-6.8), respectively. In summary, we developed and independently validated a version 2.0 KidneyIntelX with previously established biomarkers combined with selected clinical variables and demonstrated robust prediction of progressive decline in kidney function, independent of common risk factors. Disclosure G.N.Nadkarni: Advisory Panel; Renalytix, Consultant; Renalytix, Other Relationship; Renalytix, Speaker's Bureau; Daiichi Sankyo, GlaxoSmithKline plc., Menarini Group, Stock/Shareholder; Renalytix. F.Fleming: Employee; Renalytix. M.J.Donovan: Employee; Renalytix. S.Coca: Advisory Panel; Renalytix, Bayer Inc., Boehringer Ingelheim International GmbH, Consultant; Renalytix, Nuwellis, 3ive Labs, Reprieve Cardiovascular, Vifor Pharma Management Ltd., Stock/Shareholder; Renalytix. Funding Renalytix

1077-P: A Multicenter Initiative to Improve Care in Cardiometabolic Disease—Initial Report From Cardiometabolic Center Alliance (CMCA)

Background: Despite high risk, minority of individuals with Type 2 diabetes (T2D) and cardiovascular or chronic kidney disease (CVD/CKD) receives optimal guideline directed medical therapy (GDMT). Professional societies advocate for collaborative, team-based models to improve care in this group but successful multicenter implementation efforts are lacking. Methods: CMCA is a non for profit organization that seeks to transform care and outcomes in individuals with cardiometabolic disease. CMCA assists members in implementing team-based, coordinated care models (Cardiometabolic Centers) and GDMT driven pathways. Quality of care and outcomes are monitored via multicenter registry. Since launch in 2020, 14 US organizations joined CMCA. This initial report includes sites with data reported for ≥30 participants (each with ≥ 2 visits). Results: In total 606 individuals with T2D and CVD/CKD from 6 sites were evaluated (age 64 years, 44% women, 78% white, median follow up 6 months). After initiation of care at CMCA sites, large improvements in GDMT and reductions in weight, HbA1c, blood pressure, total/LDL cholesterol, triglycerides, and insulin requirements were observed (Figure panels 1 and 2; p&amp;lt; 0.001 for all). Conclusion: CMCA directed implementation of coordinated team-based care produced rapid and large improvements in GDMT and quality of care across multiple sites. Disclosure M.N.Kosiborod: Consultant; Alnylam Pharmaceuticals, Inc., Amgen Inc., Applied Therapeutics Inc., AstraZeneca, Bayer Inc., Boehringer Ingelheim Inc., Cytokinetics Inc., Dexcom, Inc., Eli Lilly and Company, ESPERION Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Merck &amp; Co., Inc., Novo Nordisk, Pharmacosmos A/S, Pfizer Inc., Sanofi, Vifor Pharma Management Ltd., Youngene Therapeutics, Other Relationship; AstraZeneca, Research Support; AstraZeneca, Boehringer Ingelheim Inc. E.Fryoux: None. L.Harness: None. R.Heath: None. K.A.Miller: None. I.Neeland: Consultant; Nestlé Health Science, Speaker's Bureau; Boehringer Ingelheim and Eli Lilly Alliance, Bayer Inc. S.Patel: None. J.Plutzky: Advisory Panel; ESPERION Therapeutics, Inc., Consultant; Amgen Inc., Merck &amp; Co., Inc., Novo Nordisk, Research Support; Boehringer Ingelheim Inc. R.K.Saalfeld: None. A.Stafos: None. S.Rajagopalan: Advisory Panel; Novartis, Novo Nordisk, Speaker's Bureau; Novo Nordisk. M.L.Magwire: Consultant; AstraZeneca, Novo Nordisk. D.S.Aistrope: None. E.Andaya: None. J.Butler: Consultant; Abbott,, Amgen, Applied Therapeutics, Array, Astra Zeneca, Bayer,, Boehringer Ingelheim, Bristol Myers Squibb, CVRx, G3 Pharma,, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, NovoNordisk, Relypsa, Roche, Sequana Medical, Vifor, Speaker's Bureau; Novartis, Boehringer Ingelheim-Lilly, Astra Zeneca, Janssen. K.Cummings: None. L.Davis: Speaker's Bureau; Amgen Inc. R.H.Eckel: Advisory Panel; Amarin Corporation, 89bio, Inc., Novo Nordisk, Weight Watchers International, Board Member; Lexicon Pharmaceuticals, Inc., Consultant; Amgen Inc., Better Therapeutics, Inc, The Healthy Aging Company, Other Relationship; Arrowhead Pharmaceuticals, Inc. J.A.Fialkow: Speaker's Bureau; Amgen Inc., ESPERION Therapeutics, Inc., Amarin Corporation. Funding AstraZeneca; Boehringer Ingelheim; Novo Nordisk, Amgen Inc.; Eli Lilly and Company; Novartis

Measurement of changes in uterine and fibroid volume during treatment of heavy menstrual bleeding (HMB).

Does application of an unbiased method for analysis of magnetic resonance (MR) images reveal any effect on uterine or fibroid volume from treatment of heavy menstrual bleeding (HMB) with three 12-week courses of the selective progesterone receptor modulator ulipristal acetate (SPRM-UPA)? Application of an unbiased method for analysis of MR images showed that treatment of HMB with SPRM-UPA was not associated with a significant reduction in the volume of the uterus or in the volume of uterine fibroids. SPRM-UPA shows therapeutic efficacy for treating HMB. However, the mechanism of action (MoA) is not well understood and there have been mixed reports, using potentially biased methodology, regarding whether SPRM-UPA has an effect on the volume of the uterus and fibroids. In a prospective clinical study (with no comparator), 19 women with HMB were treated over a period of 12 months with SPRM-UPA and uterine and fibroid size were assessed with high resolution structural MRI and stereology. A cohort of 19 women aged 38-52years (8 with and 11 without fibroids) were treated with three 12-week courses of 5 mg SPRM-UPA given daily, with four weeks off medication in-between treatment courses. Unbiased estimates of the volume of uterus and total volume of fibroids were obtained at baseline, and after 6 and 12 months of treatment, by using the Cavalieri method of modern design-based stereology in combination with magnetic resonance imaging (MRI). Bland-Altman plots showed good intra-rater repeatability and good inter-rater reproducibility for measurement of the volume of both fibroids and the uterus. For the total patient cohort, two-way ANOVA did not show a significant reduction in the volume of the uterus after two or three treatment courses of SPRM-UPA (P = 0.51), which was also the case when the groups of women with and without fibroids were considered separately (P = 0.63). One-way ANOVA did not show a significant reduction in total fibroid volume in the eight patients with fibroids (P = 0.17). The study has been performed in a relatively small cohort of women and simulations that have subsequently been performed using the acquired data have shown that for three time points and a group size of up to 50, with alpha (Type I Error) and beta (Type II Error) set to 95% significance and 80% power, respectively, at least 35 patients would need to be recruited in order for the null hypothesis (that there is no significant reduction in total fibroid volume) to be potentially rejected. The imaging protocol that we have developed represents a generic paradigm for measuring the volume of the uterus and uterine fibroids that can be readily incorporated in future studies of medical treatments of HMB. In the present study, SPRM-UPA failed to produce a significant reduction in the volume of the uterus or the total volume of fibroids (which were present in approximately half of the patients) after either two or three 12-week courses of treatment. This finding represents a new insight in respect of the management of HMB using treatment strategies that target hormone-dependence. The UPA Versus Conventional Management of HMB (UCON) trial was funded by the EME Programme (Medical Research Council (MRC) and National Institutes of Health Research (NIHR)) (12/206/52). The views expressed in this publication are those of the authors and not necessarily those of the Medical Research Council, National Institute for Health Research, or Department of Health and Social Care.Medical Research Council (MRC) Centre grants to the Centre for Reproductive Health (CRH) (G1002033 and MR/N022556/1) are also gratefully acknowledged. H.C. has clinical research support for laboratory consumables and staff from Bayer AG and provides consultancy advice (All paid to Institution) for Bayer AG, PregLem SA, Gedeon Richter, Vifor Pharma UK Ltd, AbbVie Inc., and Myovant Sciences GmbH. H.C. has received royalties from UpToDate for an article on abnormal uterine bleeding. L.W. has received grant funding from Roche Diagnostics (Paid to Institution). All other authors have no conflicts to declare. The study reported here is an embedded mechanism of action study (no comparator) within the UCON clinical trial (registration ISRCTN: 20426843).

Kidney Disease Patient Representation in Trials of Combination Therapy With VEGF-Signaling Pathway Inhibitors and Immune Checkpoint Inhibitors: A Systematic Review

Kidney Disease Patient Representation in Trials of Combination Therapy With VEGF-Signaling Pathway Inhibitors and Immune Checkpoint Inhibitors: A Systematic Review

An essential role of iron in Tfh cell development and effector function

Abstract Background: T follicular helper CD4+ cells (Tfh) are essential for maintenance of systemic lupus erythematosus (SLE) as they help germinal center B cells generate high affinity auto-antibodies. The activation of STAT3 is critical for generation of Tfh cells as it promotes the transcription of BCL6 (the essential transcription factor for Tfh cell differentiation). It is recognized that activated, proliferating SLE CD4+ T cells, contain more iron than controls. Iron binds CDK1 to accentuate JAK1 phosphorylation and activation of STAT3 in proliferating cells. Whether increased iron content of SLE CD4+ T cells augments JAK1-STAT3 signaling and their differentiation into Tfh cells has not been investigated. Experiments: RNAseq and qPCR was used to compare iron regulatory pathways in purified Tfh cells from WT and SLE-prone mice. Labile iron (bio-active) content was measured in freshly isolated Tfh cells. The effect of iron chelator on in vitro Tfh differentiation and effector function was evaluated. Results: Compared to WT, SLE Tfh cells displayed significant increase in genes associated with iron uptake and transmembrane iron transport. Labile iron content and CDK1 gene expression were elevated in SLE Tfh cells. Iron chelation attenuated STAT3 activation, BCL6 expression and IL-21 production in in vitro generated Tfh cells. Conclusion: Our novel data identify an essential role of iron in Tfh cell differentiation and effector function. Increased iron and CDK1 may amplify JAK1-STAT3 signaling and potentiate Tfh cell differentiation. This can be blocked by restricting free iron availability. Understanding this aspect of Tfh cell biology in SLE may support strategies that control labile iron as potential adjunct therapy. Supported by grants from Vifor Pharma (P0213104, P0226952) to Yogesh Scindia NIH (R01AI135128) to Borna Mehrad NIH (R01AI128901) to Laurence Morel

E038 A common measure of the impact of glucocorticoids in patients with inflammatory and autoimmune conditions - the Steroid PRO: A cross-cultural validation study with Rasch models

Abstract Background/Aims Systemic glucocorticoids are key in the management of life- and organ-threatening rheumatic diseases, but have wide-ranging adverse effects of concern to patients and clinicians. We aimed to validate a Patient Reported Outcome (PRO) measure (the Steroid PRO) for assessing the impact of glucocorticoids on health-related quality of life (HRQoL) in patients receiving glucocorticoids for rheumatic disease. Methods This was a cross-sectional study of adults from the UK, USA, Australia and New Zealand, taking glucocorticoids for a rheumatic disease. An online survey was conducted at two time points: Time 1: (i) demographics - age, gender, country, ethnicity, educational level; (ii) clinical information - diagnosis, glucocorticoid dose; (iii) 40 candidate items for the Steroid-PRO, developed in a previous qualitative study; (iv) EQ5D-5L. Time 2 (optional, completed 3-5 days later): (i) the Steroid PRO candidate items; (ii) a condition change question. The survey was distributed via social media and patient organisations. After descriptive analysis, iterative testing with Rasch measurement model and exploratory factor analysis (EFA) informed item reduction and established structural validity, reliability and unidimensionality of the final Steroid-PRO. Item reduction was based on clinical importance, lack of fit to the Rasch model, and redundancy. Evidence of discriminative validity of the Steroid-PRO was established by comparing its scores for participants receiving lower dose glucocorticoid (up to 10 mg) versus higher dose (&amp;gt;10 mg). Intraclass correlation (ICC) between Time 1 and Time 2 was calculated for patients who reported ‘no change’ compared with 3-5 days ago. Results A total of 946 patients returned complete responses at Time 1 (Time 2: 447 responses). They were from UK, n = 743 (78.5%); USA, n = 139 (14.7%); Australia, n = 59 (6.2%). Their mean age was 57.6 (SD = 13.6); 833 (88%) were women. They were treated for inflammatory arthritis (n = 194), connective tissue disease and/or vasculitis (n = 398), and giant cell arteritis and/or polymyalgia rheumatica (n = 341). A total of 25 items were removed due to floor effects and lack of fit to the Rasch model. The remaining 15 items showed a satisfactory fit to the model. EFA suggested a scale structure with four domains: Participation (4 items), Appearance (3 items), Psychological (5 items), and Treatment concerns (3 items). This 4-domain structure was supported by the Rasch model, confirming construct validity; χ2=47.82 (DF = 36), p = 0.899; and reliability (Person Separation Index, PSI=0.757). Patients on a lower glucocorticoid dose had lower Steroid-PRO domain scores than those receiving higher dose (discriminant validity). ICC between Time 1 and Time 2 ranged from 0.892 to 0.942 (95%CI 0.868 to 0.953) suggesting excellent (test-retest) reliability. Conclusion The final Steroid-PRO is a 15-item, valid and reliable 4-domain scale measuring the impact of glucocorticoid therapy on HRQoL of people with rheumatic diseases. Disclosure S. Bridgewater: Grants/research support; S.B. has received funding for research from Vifor Pharma. M. Ndosi: Grants/research support; M.N. has received funding for research from Vifor Pharma. J. Dawson: None. P. Richards: None. C. Silverthorne: None. E. Dures: Grants/research support; E.D. has received funding for research from Vifor Pharma. S. Goodman: Consultancies; S.G. reports consultancy for UCB. Grants/research support; S.G. has received research support from Novartis. Other; S.G. has given talks for NYU, Case Western, ACR Rheumatology Courses. C. Hill: None. S.L. Mackie: Consultancies; S.L.M. has provided consultancy on behalf of her institution for Roche/Chugai, Sanofi, AbbVie, AstraZeneca. Grants/research support; S.L.M. has been an investigator on clinical trials for Sanofi and GSK, as a research grant co-applicant, S.L.M. has received research funding (partial salary support) from Vifor, paid to her institution. Other; S.L.M. has given talks on behalf of her institution for Pfizer, Vifor and UCB. In all cases fees were paid to her institution and no personal fees were received, S.L.M. was supported by Roche to attend EULAR2019 and by Pfizer to attend ACR2021 virtually. J.C. Robson: Consultancies; J.C.R. reports: Consultancy for Vifor Pharma. Grants/research support; Funding for research from Vifor Pharma. Other; Speaking fees from Vifor Pharma.

Time to reconsider the perception and management of hypertensive heart disease.

Time to reconsider the perception and management of hypertensive heart disease.

Characterization and prognosis of very elderly patients with anemia, cardio-cerebrovascular disease, and iron deficiency in four Portuguese hospitals.

To the Editor Cardiovascular disease (CVD) is the leading cause of death in Portugal.1 Anemia and iron deficiency (ID) are commonly present in the elderly and associated with adverse clinical outcomes.2,3 Portuguese data describing elderly and very elderly (VEP) patients are scarce, making it critical to characterize this population and obtain data on the actual dimension of their major clinical issues. This study aimed to characterize and evaluate the prognosis of VEP with anemia and CVD in four Portuguese hospitals. Data from all patients admitted to the internal medicine wards in 2017 who fulfilled the study inclusion criteria, including being VEP (≥aged 80 years or older) and diagnosed with anemia and CVD at the time of admission, were obtained. Authorizations were obtained from all the ethics committees/institutional review boards from all the hospitals involved in this study. Of the 16 446 patients admitted to the hospitals, 514 met the inclusion criteria. The median age of VEP was 86 years (interquartile range [IQR]: 83–89), 64.4% were female, and 81.5% resided in their homes. At admission, median hemoglobin was 10.7 g/dL [IQR: 9.57–11.5], median serum iron was 34 µg/dL [IQR: 25–50.5], median ferritin was 117.8 µg/dL [IQR: 59.73–246.5], and median transferrin saturation was 12% [IQR: 7–17.7]. The median hospitalization length was 8.5 days [IQR: 5–13]. The mortality rate for 18 months after discharge was 39.9%, and the 30-day readmission rate was 16.5%. Only 302 patients (59.0%) had serum iron and ferritin levels data. Globally, 7.0% of patients (n = 36) had ferritin levels below 30 µg/L, and 21% were on iron supplements. Mortality had a significant association with length of hospitalization (odds ratio [OR], 1.057, 95% confidence interval [CI]: 1.030–1.084, P = .001, calculated with multiple logistic regression model), age at admission (OR, 1.508, 95% CI: 1.033–2.201, P = .033, calculated with multiple logistic regression model), and hemoglobin levels (OR, 0.667, 95% CI: 0.414–1.073, P = .019, calculated with multiple logistic regression model). Regarding prognosis, the mortality rates of patients with and without ID were 25.7% and 46.5% (P = .028, calculated with the Fisher exact test). Although anemia is a widely recognized risk factor for morbidity and mortality, it remains underestimated and unexplored in VEP. Accordingly, iron parameters were unavailable in this study for many patients hospitalized with anemia and CVD. Our study revealed that VEP at a higher age, with more prolonged hospitalizations and lower hemoglobin levels, were more likely to die within 18 months after discharge. ID was associated with a worse prognosis, but further studies are needed. Notably, the authors acknowledge the limitations of this study because of its retrospective nature and the consequent inability to control the recording of data in the clinical reports. In conclusion, our study suggests that VEP with anemia and CVD may have higher mortality, which may be predicted from admission. We consider these results to warrant further investigation. Contributors RR was responsible for data curation, draft preparation, and final revision. MM, AB, and SP were responsible for data curation and draft preparation. EG was responsible for conceptualization and draft preparation. DB and AV were responsible for methodology and draft preparation. MS was responsible for the investigation and draft preparation. AM was responsible for the formal analysis. Funding Financial support and sponsorship: Vifor Pharma provided support for third-party medical writing assistance for this manuscript. The sponsor had no role in the study design, data analysis and interpretation, report writing, or the decision to submit this study. Conflicts of interest The authors report no conflicts of interest.

Ferric carboxymaltose infusion versus oral iron supplementation for preoperative iron deficiency anaemia in patients with colorectal cancer (FIT): a multicentre, open-label, randomised, controlled trial

A third of patients with colorectal cancer who are eligible for surgery in high-income countries have concomitant anaemia associated with adverse outcomes. We aimed to compare the efficacy of preoperative intravenous and oral iron supplementation in patients with colorectal cancer and iron deficiency anaemia. In the FIT multicentre, open-label, randomised, controlled trial, adult patients (aged 18 years or older) with M0 stage colorectal cancer scheduled for elective curative resection and iron deficiency anaemia (defined as haemoglobin level of less than 7·5 mmol/L (12 g/dL) for women and less than 8 mmol/L (13 g/dL) for men, and a transferrin saturation of less than 20%) were randomly assigned to either 1-2 g of ferric carboxymaltose intravenously or three tablets of 200 mg of oral ferrous fumarate daily. The primary endpoint was the proportion of patients with normalised haemoglobin levels before surgery (≥12 g/dL for women and ≥13 g/dL for men). An intention-to-treat analysis was done for the primary analysis. Safety was analysed in all patients who received treatment. The trial was registered at ClincalTrials.gov, NCT02243735, and has completed recruitment. Between Oct 31, 2014, and Feb 23, 2021, 202 patients were included and assigned to intravenous (n=96) or oral (n=106) iron treatment. Treatment began a median of 14 days (IQR 11-22) before surgery for intravenous iron and 19 days (IQR 13-27) for oral iron. Normalisation of haemoglobin at day of admission was reached in 14 (17%) of 84 patients treated intravenously and 15 (16%) of 97 patients treated orally (relative risk [RR] 1·08 [95% CI 0·55-2·10]; p=0·83), but the proportion of patients with normalised haemoglobin significantly increased for the intravenous treatment group at later timepoints (49 [60%] of 82 vs 18 [21%] of 88 at 30 days; RR 2·92 [95% CI 1·87-4·58]; p<0·0001). The most prevalent treatment-related adverse event was discoloured faeces (grade 1) after oral iron treatment (14 [13%] of 105), and no treatment-related serious adverse events or deaths were observed in either group. No differences in other safety outcomes were seen, and the most common serious adverse events were anastomotic leakage (11 [5%] of 202), aspiration pneumonia (5 [2%] of 202), and intra-abdominal abscess (5 [2%] 202). Normalisation of haemoglobin before surgery was infrequent with both treatment regimens, but significantly improved at all other timepoints following intravenous iron treatment. Restoration of iron stores was feasible only with intravenous iron. In selected patients, surgery might be delayed to augment the effect of intravenous iron on haemoglobin normalisation. Vifor Pharma.

Non-erythropoiesis stimulating agent, non-iron therapies for the management of anemia: A scoping review.

Non-erythropoiesis stimulating agent, non-iron therapies for the management of anemia: A scoping review.

Factors associated to renin-angiotensin-aldosterone system inhibitors discontinuation or down-titration due to hyperkalaemia in patients with chronic cardiovascular conditions

Abstract Background/Introduction The renin-angiotensin-aldosterone system inhibitors (RAASI) are one of the keystones of the medical treatment in chronic cardiovascular disorders and have shown improvements in clinical outcomes in many clinical trials. Hyperkalaemia is a well-defined non-desirable effect of RAASI that occasionally forces to interrupt these medications. That enforced RAASI discontinuation or down-titration due to hyperkalaemia may have adverse prognostic consequences. Purpose Describe the demographical, clinical and pharmacological variables associated to a higher risk of RAASI discontinuation or down-titration due to hyperkalaemia among individuals with chronic cardiovascular conditions. Methods We used data from more than 375,000 individuals 55 years of age or older, included in the population-based healthcare database of a public Institute of Health between 2015 and 2017. We included participants with at least one relevant condition: chronic heart failure, chronic kidney disease, diabetes mellitus, ischemic heart disease or hypertension. They had to be under RAASI treatment as of January 1st, 2016, and with evidence of at least one episode of hyperkalaemia (serum potassium &amp;gt;5.0 mmol/L) during 2016. Then, were classified in one of the two following profiles: RAASI treatment discontinuation or down-titration versus RAASI treatment unchanged or up-titrated. For the statistical analysis, we used logistic regression to calculate the multivariable-adjusted odds ratios of each study variable, comparing RAASI discontinuation or down-titration group to RAASI treatment unchanged or up-titrated controls (reference group). Results In the multivariable-adjusted model, the risk of RAASI treatment discontinuation or down-titration due to hyperkalaemia was significantly associated with the use of RAASI, very high comorbidity index, potassium derangements (both hypokalaemia and hyperkalaemia), prior hospitalizations and prior emergency visits. Among RAASI treatments, the use of Angiotensin receptor blockers (OR 2.518, 95% CI 2.317–2.735) and Angiotensin-converting enzyme inhibitors (OR 2.341, 95% CI 2.149–2.549) were associated with a higher risk of RAASI discontinuation or down-titration due to hyperkalaemia than Aldosterone inhibitors (1.428, 95% CI 1.285–1.584). Conclusion These results suggest that vulnerable populations such as those with very high comorbidity index, potassium derangements or prior emergency visits or hospitalizations have a higher risk of RAASI treatment discontinuation or down-titration due to hyperkalaemia. A more careful and exhaustive management of RAASI should be advised in those patients. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Josep Comin-Colet has received speaker fees from Vifor Pharma.