Bayer AG Research Articles

MP79-09 LONG-TERM TESTOSTERONE THERAPY IN MEN WITH FUNCTIONAL HYPOGONADISM IMPROVES KIDNEY FUNCTION

You have accessJournal of UrologyCME1 Apr 2023MP79-09 LONG-TERM TESTOSTERONE THERAPY IN MEN WITH FUNCTIONAL HYPOGONADISM IMPROVES KIDNEY FUNCTION Ahmad Haider, Karim Sultan Haider, Gheorghe Doros, and Abdulmaged Traish Ahmad HaiderAhmad Haider More articles by this author , Karim Sultan HaiderKarim Sultan Haider More articles by this author , Gheorghe DorosGheorghe Doros More articles by this author , and Abdulmaged TraishAbdulmaged Traish More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003356.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Testosterone deficiency is a prevalent condition in men with chronic kidney disease. We investigated effects of testosterone therapy on renal parameters and renal function in men with functional hypogonadism. METHODS: 898 men with hypogonadism, 481 men chose TTh by means of testosterone undecanoate (TU) injections 1000 mg/12 weeks following an initial 6-week interval (T-group). 417 men opted against TTh and served as controls (CTRL). 14-year data are presented.Changes over time between groups were compared and adjusted for age, weight, waist circumference, fasting glucose, blood pressure, lipids and quality of life to account for baseline differences between the groups.Means and standard deviations of absolute measures over 14 years are reported.eGFR was calculated using the Modification of Diet in Renal Disease (MDRD) formula. RESULTS: Baseline age was 56.5±8.0 years in the T-group and 62.7±5.3 years in CTRL (p<0.0001). Mean follow-up was 11.0±3.2 years in the T-group and 11.1±3.3 in CTRL. Median follow-up was 12 years in the T-group and 12 years in CTRL.Creatinine (mg/dL) decreased by 0.10±0.03 at 14 years in the T-group (p<0.005) and increased by 0.33±0.04 in CTRL (p<0.0001). Estimated adjusted difference between groups at 14 years was -0.50 [95% CI: -0.58;-0.41] (p<0.0001). γGT (U/L) decreased by 24.0±0.7 at 14 years in the T-group and increased by 26.2±0.8 in CTRL, estimated adjusted difference between groups at 14 years: -47.3 [95% CI: -49.4;-45.1] (p<0.0001 for all). eGFR-(MDRD) (mL/min/1.73 m2) increased by 10.3±0.7 in T-group, reaching a peak in year 8 with a small but steady decline thereafter. eGFR-MDRD decreased progressively by 27.3±0.8 in CTRL. Estimated adjusted difference between groups at year 14: 41.5 [95% CI: 39.5;43.6] (p<0.0001 for all). Systolic blood pressure (mmHg) decreased in the T-group by 23.5±0.7 and increased in CTRL by 21.6±0.8. Estimated adjusted difference between groups: -38.1 [95% CI: -40.2;-35.9] (p<0.0001 for all). Diastolic blood pressure (mmHg) decreased by 14.7±0.5 (T-group) and increased by 14.3±0.5 (CTRL). Estimated adjusted difference between groups: -25.0 [95% CI: -26.5;-23.6] (p<0.0001 for all). During the entire observation period, 49 deaths (10,2%) occurred in the T-group. In CTRL, 133 deaths (31.9%) were recorded. All injections were administered in the office and documented. CONCLUSIONS: Long-term testosterone therapy in men with hypogonadism improves renal function demonstrated by eGFR, potentially contributing to reduced mortality. Source of Funding: Data entry was compensated by Bayer AG © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1144 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ahmad Haider More articles by this author Karim Sultan Haider More articles by this author Gheorghe Doros More articles by this author Abdulmaged Traish More articles by this author Expand All Advertisement PDF downloadLoading ...

PD23-09 LUTS, ED, AND QOL IMPROVE UNDER LONG-TERM TESTOSTERONE THERAPY IN OBESE MEN WITH FUNCTIONAL HYPOGONADISM

You have accessJournal of UrologyCME1 Apr 2023PD23-09 LUTS, ED, AND QOL IMPROVE UNDER LONG-TERM TESTOSTERONE THERAPY IN OBESE MEN WITH FUNCTIONAL HYPOGONADISM Ahmad Haider, Karim Sultan Haider, Gheorghe Doros, and Abdulmaged Traish Ahmad HaiderAhmad Haider More articles by this author , Karim Sultan HaiderKarim Sultan Haider More articles by this author , Gheorghe DorosGheorghe Doros More articles by this author , and Abdulmaged TraishAbdulmaged Traish More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003296.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) in elderly men are closely associated with quality of life (QoL). We aimed to assess long-term effects of testosterone therapy (TTh) in hypogonadal men in a registry study. METHODS: 898 men with hypogonadism, 481 men chose TTh by means of testosterone undecanoate (TU) injections 1000 mg/12 weeks following an initial 6-week interval (T-group). 417 men opted against TTh and served as controls (CTRL). 14-year data are presented. Changes over time between groups were compared and adjusted for age, weight, waist circumference, fasting glucose, blood pressure, lipids and quality of life to account for baseline differences between the groups. Means and standard deviations of absolute measures over 14 years are reported. RESULTS: Baseline age was 56.5±8.0 years in the T-group and 62.7±5.3 years in CTRL (p<0.0001). Mean follow-up was 11.0±3.2 years in the T-group and 11.1±3.3 in CTRL. Median follow-up was 12 years in the T-group and 12 years in CTRL. At baseline, alpha-blockers were used by 36.6% (T-group) and 50.2% (CTRL) (p<0.0001), 5α-reductase inhibitors by 2.1% and 8.6% (p<0.0001), and PDE5-Inhibitors by 26.4% and 22.1% (p=0.1308). IPSS (baseline: 6.4±3.7) decreased to 1.5±0.7 (p<0.0001) in the T-group in year 14. In CTRL, IPSS (baseline: 4.9±1.9) increased to 11.4±5.1 (p<0.0001). Estimated adjusted difference between groups: -11.0 (p<0.0001). Residual bladder volume (RBV) in the T-group (baseline: 50.7±25.9) decreased by 39.3±1.4 mL (p<0.0001) in year 14. In CTRL, RBV (baseline: 51.7±16.7) increased by 58.8±1.5 mL (p<0.0001). Estimated adjusted difference between groups: -94.4 mL [95% CI: -98.2;-90.7] (p<0.0001). IIEF-EF in the T-group increased from 17.3±5.9 (mild to moderate) by 11.1±0.2 to 29.5±0.9 (no ED) in year 14. In CTRL, IIEF-EF decreased from 19.7±3.5 (mild to moderate) by 14.5±0.2 to 6.8±0.9 (severe). Estimated adjusted difference between groups: 23.5 (95% CI: 23.0;24.1) (p<0.0001). QoL, assessed by the Aging Males’ Symptoms scale (AMS), improved from 53.0±9.8 (severe symptoms) by 29.8 points in the T-group to 17.2 (no symptoms) and worsened from 40.4±5.6 (moderate symptoms) by 24.7 points to 66.7 (severe symptoms) in CTRL. CONCLUSIONS: In men with functional hypogonadism, long-term TTh improves LUTS and ED sustainably over 14 years. This may have contributed to improvements in QoL. In the untreated control group, LUTS, ED, and QoL deteriorated. Source of Funding: Data entry was compensated by Bayer AG © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e675 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ahmad Haider More articles by this author Karim Sultan Haider More articles by this author Gheorghe Doros More articles by this author Abdulmaged Traish More articles by this author Expand All Advertisement PDF downloadLoading ...

MP29-02 EFFICACY AND SAFETY OF DAROLUTAMIDE IN COMBINATION WITH ANDROGEN-DEPRIVATION THERAPY AND DOCETAXEL IN THE NORTH AMERICAN POPULATION FROM ARASENS

You have accessJournal of UrologyCME1 Apr 2023MP29-02 EFFICACY AND SAFETY OF DAROLUTAMIDE IN COMBINATION WITH ANDROGEN-DEPRIVATION THERAPY AND DOCETAXEL IN THE NORTH AMERICAN POPULATION FROM ARASENS Neal D. Shore, Bertrand Tombal, Maha Hussain, Fred Saad, Karim Fizazi, Cora N. Sternberg, E. David Crawford, Luke Nordquist, Ronald Tutrone, Laurence Belkoff, Shivani Kapur, Jay Jhaveri, Shankar Srinivasan, Heikki Joensuu, and Matthew R. Smith Neal D. ShoreNeal D. Shore More articles by this author , Bertrand TombalBertrand Tombal More articles by this author , Maha HussainMaha Hussain More articles by this author , Fred SaadFred Saad More articles by this author , Karim FizaziKarim Fizazi More articles by this author , Cora N. SternbergCora N. Sternberg More articles by this author , E. David CrawfordE. David Crawford More articles by this author , Luke NordquistLuke Nordquist More articles by this author , Ronald TutroneRonald Tutrone More articles by this author , Laurence BelkoffLaurence Belkoff More articles by this author , Shivani KapurShivani Kapur More articles by this author , Jay JhaveriJay Jhaveri More articles by this author , Shankar SrinivasanShankar Srinivasan More articles by this author , Heikki JoensuuHeikki Joensuu More articles by this author , and Matthew R. SmithMatthew R. Smith More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003257.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: In ARASENS (NCT02799602), darolutamide (DARO) + androgen-deprivation therapy (ADT) + docetaxel significantly reduced the risk of death by 32.5% (HR 0.68, 95% CI 0.57–0.80; P<0.0001) vs placebo (PBO) + ADT + docetaxel in patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC). DARO maintained quality of life, with similar control of disease-related physical symptoms and pain vs placebo, and had a favorable safety profile. We report clinical outcomes in North American (NA) pts in ARASENS. METHODS: This international, double-blind, phase 3 trial randomized pts 1:1 to DARO 600 mg twice daily or PBO in addition to ADT + docetaxel. The primary endpoint was overall survival (OS). Key secondary endpoints included time to castration-resistant prostate cancer (CRPC) and safety. RESULTS: Of 1305 pts analyzed, 244 (18.7%) were enrolled in North America (US/Canada 218/26; DARO/PBO 125/119) and of these, 36 (14.8%) were Black/African American (AA) pts. Baseline characteristics of the NA population were generally similar to those of the overall population, except for the proportion of pts with de novo metastatic disease (75.8% NA vs 86.1% overall). In NA pts, DARO + ADT + docetaxel was associated with OS benefit vs PBO + ADT + docetaxel (HR 0.59, 95% CI 0.39–0.89), with 4-year survival rates of 66% vs 50%, respectively. The DARO vs PBO group had longer time to CRPC (HR 0.32, 95% CI 0.21–0.48). The safety profile of DARO in NA pts was consistent with that of the overall population (grade 3/4 treatment-emergent adverse events [TEAEs] 61% NA vs 66% overall; serious TEAEs 44% NA vs 45% overall). The incidences of TEAEs associated with androgen receptor pathway inhibition for DARO vs PBO were generally consistent, particularly when adjusted for treatment exposure. The OS benefit and safety profile of DARO vs PBO was also seen in Black/AA pts, consistent with the overall population. CONCLUSIONS: In NA pts with mHSPC, addition of DARO to ADT + docetaxel led to a clinically meaningful reduction in risk of death by 41% and improved the key patient-relevant secondary endpoint of time to CRPC. Incidences of TEAEs were generally similar between treatment groups in NA pts and consistent with the overall population. Source of Funding: Bayer AG and Orion Pharma. © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e380 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Neal D. Shore More articles by this author Bertrand Tombal More articles by this author Maha Hussain More articles by this author Fred Saad More articles by this author Karim Fizazi More articles by this author Cora N. Sternberg More articles by this author E. David Crawford More articles by this author Luke Nordquist More articles by this author Ronald Tutrone More articles by this author Laurence Belkoff More articles by this author Shivani Kapur More articles by this author Jay Jhaveri More articles by this author Shankar Srinivasan More articles by this author Heikki Joensuu More articles by this author Matthew R. Smith More articles by this author Expand All Advertisement PDF downloadLoading ...

MP29-01 RAPID, DURABLE, AND DEEP PROSTATE-SPECIFIC ANTIGEN RESPONSE FOLLOWING ADDITION OF DAROLUTAMIDE TO ANDROGEN-DEPRIVATION THERAPY AND DOCETAXEL IN ARASENS

You have accessJournal of UrologyCME1 Apr 2023MP29-01 RAPID, DURABLE, AND DEEP PROSTATE-SPECIFIC ANTIGEN RESPONSE FOLLOWING ADDITION OF DAROLUTAMIDE TO ANDROGEN-DEPRIVATION THERAPY AND DOCETAXEL IN ARASENS Fred Saad, Bertrand Tombal, Maha Hussain, Karim Fizazi, Cora N. Sternberg, E. David Crawford, Luke T. Nordquist, Ronald Tutrone, Neal D. Shore, Laurence Belkoff, Shivani Kapur, Jay Jhaveri, Jorge Ortiz, Shankar Srinivasan, Frank Verholen, and Matthew R. Smith Fred SaadFred Saad More articles by this author , Bertrand TombalBertrand Tombal More articles by this author , Maha HussainMaha Hussain More articles by this author , Karim FizaziKarim Fizazi More articles by this author , Cora N. SternbergCora N. Sternberg More articles by this author , E. David CrawfordE. David Crawford More articles by this author , Luke T. NordquistLuke T. Nordquist More articles by this author , Ronald TutroneRonald Tutrone More articles by this author , Neal D. ShoreNeal D. Shore More articles by this author , Laurence BelkoffLaurence Belkoff More articles by this author , Shivani KapurShivani Kapur More articles by this author , Jay JhaveriJay Jhaveri More articles by this author , Jorge OrtizJorge Ortiz More articles by this author , Shankar SrinivasanShankar Srinivasan More articles by this author , Frank VerholenFrank Verholen More articles by this author , and Matthew R. SmithMatthew R. Smith More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003257.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: In ARASENS (NCT02799602), darolutamide (DARO) in combination with androgen-deprivation therapy (ADT) and docetaxel significantly reduced the risk of death by 32.5% (HR 0.68; 95% CI 0.57–0.80; P<0.0001) vs ADT + docetaxel in patients with metastatic hormone-sensitive prostate cancer (mHSPC). We report on prostate-specific antigen (PSA) responses and kinetics data from ARASENS. METHODS: Patients with mHSPC were randomized 1:1 to DARO 600 mg twice daily or placebo (PBO), both with ADT + docetaxel. Serum PSA was measured at screening and every 12 weeks. Analyses included undetectable PSA (<0.2 ng/mL), ≥50% and ≥90% reductions in PSA from baseline (PSA50, PSA90), and times to PSA progression and PSA50/PSA90. Post hoc landmark analyses evaluated the association between undetectable PSA at weeks 24 and 36 with overall survival (OS) and time to PSA progression. RESULTS: For 1305 patients in the full analysis set (DARO, 651; PBO, 654), median (range) PSA levels at study entry were 30.3 (0.0–9219.0) and 24.2 (0.0–11,947.0) ng/mL, respectively. Patients in the DARO group demonstrated rapid PSA90 response, with 67.6% achieving PSA90 within 12 weeks, 82.0% within 24 weeks, and 84.9% at any time compared with 42.8%, 54.4%, and 59.0% in the PBO group, respectively (Figure). DARO was associated with deep PSA response, with median PSA at nadir of 0.020 ng/mL vs 0.495 ng/mL for PBO. Undetectable PSA was achieved in more than twice the number of patients receiving DARO vs PBO at 24 weeks (48.7% vs 23.9%), continuing to increase at 36 and 52 weeks with DARO (57.1% and 60.2%). Compared with patients who did not achieve undetectable PSA, patients receiving DARO who achieved undetectable PSA at 24 and 36 weeks had improved OS (HR [95% CI] 0.47 [0.35–0.63] and 0.37 [0.28–0.49]) and prolonged time to PSA progression (HR [95% CI] 0.28 [0.18–0.42] and 0.23 [0.15–0.34]), showing durable PSA response that was maintained over time. CONCLUSIONS: Patients with mHSPC receiving DARO + ADT + docetaxel achieved rapid, durable, and deep PSA responses, correlating with improved OS and prolonged time to PSA progression vs PBO + ADT + docetaxel. Source of Funding: This trial was funded by Bayer AG and Orion Corporation. © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e380 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Fred Saad More articles by this author Bertrand Tombal More articles by this author Maha Hussain More articles by this author Karim Fizazi More articles by this author Cora N. Sternberg More articles by this author E. David Crawford More articles by this author Luke T. Nordquist More articles by this author Ronald Tutrone More articles by this author Neal D. Shore More articles by this author Laurence Belkoff More articles by this author Shivani Kapur More articles by this author Jay Jhaveri More articles by this author Jorge Ortiz More articles by this author Shankar Srinivasan More articles by this author Frank Verholen More articles by this author Matthew R. Smith More articles by this author Expand All Advertisement PDF downloadLoading ...

Environmental exposure assessment of co-formulants in plant protection products under REACH.

It is a regulatory requirement to assess co-formulants in plant protection products (PPP) under the European Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) legislation. The standard environmental exposure assessment framework for chemicals under REACH is a multicompartmental mass-balanced model and, at the local scale, is designed for use with urban (wide dispersive) or industrial (point source) emissions. However, the environmental release of co-formulants used in PPP is to agricultural soil and indirectly to waterbodies adjacent to a field and, for sprayed products, to the air. The Local Environment Tool (LET) has been developed to assess these specific emission pathways for co-formulants in a local-scale REACH exposure assessment, based on standard approaches and models used for PPP. As such, it closes a gap between the standard REACH exposure model's scope and REACH requirements to assess co-formulants in PPP. When combined with the output of the standard REACH exposure model, the LET includes an estimate of the contribution from other nonagricultural background sources of the same substance. The LET is an improvement over the use of higher tier PPP models for screening purposes because it provides a simple standardized exposure scenario. A set of predefined and conservatively selected inputs allows a REACH registrant to conduct an assessment without requiring detailed knowledge of PPP risk assessment methods or typical conditions of use. The benefit to the co-formulant downstream user (formulators) is a standardized and consistent approach to co-formulant assessment, with meaningful and readily interpretable conditions of use. The LET can serve as an example to other sectors of how to address possible gaps in the environmental exposure assessment by combining a customized local-scale exposure model with the standard REACH models. A detailed conceptual explanation of the LET model is provided here together with a discussion on its use in a regulatory context. Integr Environ Assess Manag 2023;19:1544-1554. © 2023 BASF SE, Bayer AG et al. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

MPharma: health-tech start-up makes medicines affordable and accessible to patients in Africa

Learning outcomes After discussing this case, students will be able to understand the challenges faced by social entrepreneurs in starting a health-tech start-up in Africa; create and evaluate lean business models of health-tech companies as a social enterprise; evaluate how health-tech start-ups were developing innovative business models and supply chain networks to make prescription drugs accessible and available in Africa; understand how inorganic growth strategies can help health-tech start-ups scale up; and evaluate what promises investors were seeing while investing in social enterprises in the health-care sector in Africa and what social wealth they were creating. Case overview/synopsis In August 2022, Gregory Rockson (Rockson), social entrepreneur and founder of for-profit health technology (health-tech) social enterprise in Ghana, mPharma, stated that he had plans to replicate the company’s business model, which provided people access to drugs and at affordable prices, to other African nations, beyond the company’s existing footprint. However, analysts pointed out that the fragmented drug supply chain and poor regulation in the health-care market across Africa could act as a challenge for mPharma to replicate its business model successfully across the African continent. People in Africa were forced to pay higher prices to buy life-saving drugs due to the continent’s fragmented drug supply chain. To add to their woes, pharmacies struggled to keep life-saving and life-sustaining medicines in stock. Often, patients traveled miles to a pharmacy only to find out that the drugs they needed were not in stock. In addition to this, the markets were flooded with counterfeit drugs. And the Covid-19 pandemic only exacerbated the situation. mPharma managed the prescription drug inventory for pharmacies and drug suppliers using its proprietary vendor management information system. By using the technology infrastructure it had built, the company connected patients, pharmacies and hospitals through a cloud-based software. The system enabled doctors to track in real-time which drugs were available and at which location, thus giving patients reliable access to medicines. Patients registering with mPharma with their prescriptions and medical history received an alert on their mobile phones notifying them where the drugs they needed were available. mPharma bought drugs from major drug manufacturers such as Novartis International AG, Pfizer Inc. (Pfizer) and Bayer AG, on behalf of the pharmacies. This enabled the pharmacies to save on the up-front costs of stocking the drugs, reduced supply constraints and ensured availability of drugs to consumers in these underserved markets. The company had a consignment model wherein member pharmacies had to pay only for what they sold. Most pharmacies forecast the number of drugs they needed and purchased them from mPharma at pre-agreed rates. The company took the inventory liability to prevent pharmacies from going out of stock. As mPharma used its purchasing power to buy drugs in large quantities from drug manufacturers and suppliers, it was able to help patients realize cost savings of 30% to 60% in the purchase of medicines. mPharma was focusing on achieving its ambitious goal of dominating the health-care market in Africa in future. However, analysts felt that the company would face challenges related to poor regulation in the health-care market, high prices of drugs and the fragmented pharmacy retail market in the continent. Complexity academic level This case is intended for use in MBA/MS level programs as part of a course on Social Entrepreneurship, Sustainability, Business Model Innovation, Disruptive Business Models, and Supply Chain Management in the Drug Industry. Supplementary materials Teaching notes are available for educators only. Subject code CSS 3: Entrepreneurship.

Development of a soil exposure assessment for plant protection products in Brazil: Requirements, options, and recommendations.

The Brazilian Environmental Authority (IBAMA) has recently identified soil organisms as a priority area for risk assessment development for plant protection products. This includes consideration of which species in soil fauna are important to be tested for risk assessment purposes, which ecotoxicological tests should be used, and which exposure models would be suitable, considering Brazilian soils, local agricultural practices, and local biodiversity. In this brief communication, we present proposals and recommendations for the selection of appropriate regulatory exposure assessment techniques to support initial or foundation tier assessment. Integr Environ Assess Manag 2023;19:862-869. © 2022 FMC Corporation, Syngenta, Adama, Bayer AG, BASF SE. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Analysis and management of herbicidal mixtures in a high-intensity agricultural landscape in Belgium.

Water bodies located in anthropogenically influenced environments, such as agricultural landscapes, may be exposed to different chemicals simultaneously or sequentially. Yet, current environmental risk assessments focus on single active substances for unintended mixtures. For 3.5 years, the present study monitored the mixture of herbicides, within an intensively managed agricultural catchment, accompanied by a stewardship program. Twelve herbicides and one metabolite were monitored on a daily to sub-daily basis, generating a unique, high temporal resolution data set, enabling an assessment of cumulative exposure in a worst-case scenario. Analyses focused on the number of events at which the herbicide mixture concentration exceeded the regulatory accepted concentration for algae and macrophytes, based on concentration addition, and the potential factors influencing the frequency of these events are considered. A low number of individual herbicides drove the toxicity and only two of these overlapped for the two organism groups, algae and macrophytes. The observed exceedance events coincided with seasonal influences, and low rainfall during the 2011 season correlated with a highly reduced number of these events. The major influence was found to be the implementation of the stewardship program, which directed farmers to use more advanced farming techniques, avoid spillages, and other point sources. The number of exceedance events was reduced by more than half for algae (9% of the daily mean samples in 2010 and 4% in 2013) and by approximately 10 times for macrophytes (36% in 2010 to 3% in 2013). This high-resolution monitoring data set illustrates how knowledge of the influencing factors can help reduce unintended exposure to chemicals and achieve real-world improvements. Overall, a single-substance assessment is protective of mixture effects. Where mixture effects do play a role, local measures to manage point sources are more effective than changes to the desk-based environmental risk assessments that focus on diffuse sources. Integr Environ Assess Manag 2023;19:1297-1306. © 2022 Cambridge Environmental Assessments RSK ADAS Ltd and Bayer AG. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Finerenone and effects on mortality in chronic kidney disease and type 2 diabetes: a FIDELITY analysis.

Finerenone reduces the risk of cardiovascular events in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). We investigated the causes of mortality in the FIDELITY population. The FIDELITY prespecified pooled data analysis from FIDELIO-DKD and FIGARO-DKD excluded patients with heart failure and reduced ejection fraction. Outcomes included intention-to-treat and prespecified on-treatment analyses of the risk of all-cause and cardiovascular mortality. Of 13 026 patients [mean age, 64.8 years; mean estimated glomerular filtration rate (eGFR), 57.6 mL/min/1.73 m2], 99.8% were on renin-angiotensin system inhibitors. Finerenone reduced the incidence of all-cause and cardiovascular mortality vs. placebo (8.5% vs. 9.4% and 4.9% vs. 5.6%, respectively) and demonstrated significant on-treatment reductions [hazard ratio (HR), 0.82; 95% confidence interval (CI), 0.70-0.96; P=0.014 and HR, 0.82; 95% CI, 0.67-0.99; P=0.040, respectively]. Cardiovascular-related mortality was most common, and finerenone lowered the incidence of sudden cardiac death vs. placebo [1.3% (incidence rate 0.44/100 patient-years) vs. 1.8% (0.58/100 patient-years), respectively; HR, 0.75; 95% CI, 0.57-0.996; P=0.046]. The effects of finerenone on mortality were similar across all Kidney Disease: Improving Global Outcomes risk groups. Event probability with finerenone at 4 years was consistent irrespective of baseline urine albumin-to-creatinine ratio, but seemingly more pronounced in patients with higher baseline eGFR. In FIDELITY, finerenone significantly reduced the risk of all-cause and cardiovascular mortality vs. placebo in patients with T2D across a broad spectrum of CKD stages while on treatment, as well as sudden cardiac death in the intention-to-treat population. FIDELIO-DKD and FIGARO-DKD are registered with ClinicalTrials.gov, numbers NCT02540993 and NCT02545049, respectively (funded by Bayer AG).

Happy 25th Anniversary, EurJOC!

Happy 25th Anniversary, EurJOC!

Diagnostic and therapeutic roles of iron oxide nanoparticles in biomedicine.

Nanotechnology changed our understanding of physics and chemics and influenced the biomedical field. Iron oxide nanoparticles (IONs) are one of the first emerging biomedical applications of nanotechnology. The IONs are composed of iron oxide core exhibiting magnetism and coated with biocompatible molecules. The small size, strong magnetism, and biocompatibility of IONs facilitate the application of IONs in the medical imaging field. We listed several clinical available IONs including Resovist (Bayer Schering Pharma, Berlin, Germany) and Feridex intravenous (I.V.)/Endorem as magnetic resonance (MR) contrast agents for liver tumor detection. We also illustrated GastroMARK as a gastrointestinal contrast agent for MR imaging. Recently, IONs named Feraheme for treating iron-deficiency anemia have been approved by the Food and Drug Administration. Moreover, tumor ablation by IONs named NanoTherm has also been discussed. In addition to the clinical application, several potential biomedical applications of IONs including cancer-targeting capability by conjugating IONs with cancer-specific ligands, cell trafficking tools, or tumor ablation agents have also been discussed. With the growing awareness of nanotechnology, further application of IONs is still on the horizon that would shed light on biomedicine.

The Incidence and Impact of Permanent Right Ventricular Infarction on Left Ventricular Infarct Size in Patients With Inferior ST-Segment Elevation Myocardial Infarction

Mounting evidence shows that right ventricle (RV) function carries independent prognostic influence in various disease states. This study aimed to investigate the incidence and impact of permanent RV infarction in patients with inferior ST-segment elevation myocardial infarction (STEMI) and culprit lesion in the right coronary artery (RCA). In this substudy of the DANAMI-3 (DANish Study of Optimal Acute Treatment of Patients with ST-segment Elevation Myocardial Infarction) trial, cardiac magnetic resonance was performed in 291 patients at day 1 and follow-up 3 months after primary percutaneous coronary intervention of 674 patients with STEMI with the culprit lesion in the RCA. Final infarct was assessed using late gadolinium enhancement on cardiac magnetic resonance at 3 months. Patients with permanent RV infarction (20%) had lower ventricular function at follow-up; RV ejection fraction (EF) 47% ±6 versus 50% ± 5 (p <0.005) and left ventricular (LV) EF 56% ± 8 versus 60% ± 9 (p <0.006). Furthermore, patients with permanent RV infarction had a higher incidence of microvascular obstruction 39 (67%) versus 81 (39%) (p <0.001), larger final LV infarct size 16% ±8 versus 10% ± 8 (p <0.001) and larger LV area at risk 33% ± 10 versus 29% ± 9 (p <0.001). Permanent RV infarction was an independent predictor of final LV infarct size (p <0.001) but was not associated with LVEF (β=-0.0; p=0.13) in multivariable analyses. In conclusion, permanent RV infarction was seen in 20% of patients with inferior STEMI and culprit lesion in RCA and independently predicted final LV infarct size. However, permanent RV infarction did not predict overall LV function. LGE was used to detect infarct location and quantify infarct size.17 LGE in RV free wall on follow-up CMR was considered as permanent infarction. LGE images were obtained 10 minutes after intravenous injection of 0.1-mmol/kg body weight of gadolinium-based contrast (Gadovist; Bayer Schering, Berlin, Germany) using an electrocardiogram (ECG)-triggered inversion-recovery sequence. The inversion time was adjusted to null the signal from the normal myocardium. Short-axis images were acquired from the atrioventricular plane to the apex with adjacent 8-mm slices. The remaining protocol has been described previously.16.

Evaluation of SEAWAVE-QEX in a high agricultural intensity catchment in Belgium.

Pesticide surface water monitoring data have rarely been used as the only quantitative measure of exposure because the available monitoring data for most pesticides has not been considered robust enough for direct use in pesticide exposure assessments due to infrequent sampling. The cost of daily sample collection and analysis prohibits frequent sampling for most monitoring programs. In this context, a common question raised in assessments is how likely peak concentrations (i.e., annual maxima) may be missed if sampling intervals are longer than daily. The US Geological Survey developed the statistical model "seasonal wave with streamflow adjustment and extended capability" (SEAWAVE-QEX) to address the need to estimate infrequently occurring pesticide concentrations, such as annual maximum daily concentrations, for sites with nondaily monitoring data. This study compares the results of two postprocessing methods and evaluates the capability of SEAWAVE-QEX to estimate annual maximum concentrations of three commonly used herbicides and one metabolite in a catchment in Belgium. The study concludes that the appropriateness of using SEAWAVE-QEX to estimate annual maximum concentrations depends on pesticide characteristics and use and that the model can be particularly sensitive to nonflow correlated exposure events (e.g., point source contributions or drift). Integr Environ Assess Manag 2023;19:513-526. © 2022 Stone Environmental and Bayer AG Crop Science Division. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Single-Dose Bioequivalence Study of Rivaroxaban-Containing Medicinal Products in Healthy Volunteers

Therapeutically, new oral anticoagulants (NOACs) are considered to be non-inferior or superior to vitamin K antagonists (warfarin). NOACs are included in current guidelines for the treatment of various cardiovascular diseases. Rivaroxaban medicinal products have been shown to effectively fight thrombotic complications of the new coronavirus infection, COVID-19. The wide clinical use of rivaroxaban products motivates the development of generics.The aim of the study was to compare the pharmacokinetics and safety of rivaroxaban medicinal products in a single-dose bioequivalence study in healthy volunteers under fasting conditions.Materials and methods: the bioequivalence study compared single-dose oral administration of Rivaroxaban, 10 mg film-coated tablets (NovaMedica Innotech LLC, Russia), and the reference product Xarelto®, 10 mg filmcoated tablets (Bayer AG, Germany), in healthy volunteers under fasting conditions. The open, randomised, crossover trial included 46 healthy volunteers. Each of the medicinal products (the test product and the reference product) was administered once; blood samples were collected during the 48 h after the administration. The washout between the study periods lasted 7 days. Rivaroxaban was quantified in plasma samples of the volunteers by high performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS).Results: no adverse events or serious adverse events were reported for the test and reference products during the study. The following pharmacokinetic parameters were obtained for Rivaroxaban and Xarelto®, respectively: Cmax of 134.6 ± 58.0 ng/mL and 139.9 ± 49.3 ng/mL, AUC0–48 of 949.7 ± 354.5 ng×h/mL and 967.6 ± 319.9 ng×h/mL, AUC 0–∞ of 986.9 ± 379.7 ng×h/mL and 1003.6 ± 320.4 ng×h/mL, T1/2 of 8.2 ± 3.2 h and 7.8 ± 3.3 h. The 90% confidence intervals for the ratios of Cmax, AUC0–48, and AUC0–∞ geometric means were 88.04–108.67%, 89.42–104.92% and 89.44–104.81%, respectively.Conclusions: the test product Rivaroxaban and the reference product Xarelto® were found to have similar rivaroxaban pharmacokinetics and safety profiles. The study demonstrated bioequivalence of the medicinal products.

The BEEHAVEecotox Model-Integrating a Mechanistic Effect Module into the Honeybee Colony Model.

Mechanistic effect models are powerful tools for extrapolating from laboratory studies to field conditions. For bees, several good models are available that can simulate colony dynamics. Controlled and reliable experimental systems are also available to estimate the inherent toxicity of pesticides to individuals. However, there is currently no systematic and mechanistic way of linking the output of experimental ecotoxicological testing to bee models for bee risk assessment. We introduce an ecotoxicological module that mechanistically links exposure with the hazard profile of a pesticide for individual honeybees so that colony effects emerge. This mechanistic link allows the translation of results from standard laboratory studies to relevant parameters and processes for simulating bee colony dynamics. The module was integrated into the state-of-the-art honeybee model BEEHAVE. For the integration, BEEHAVE was adapted to mechanistically link the exposure and effects on different cohorts to colony dynamics. The BEEHAVEecotox model was tested against semifield (tunnel) studies, which were deemed the best study type to test whether BEEHAVEecotox predicted realistic effect sizes under controlled conditions. Two pesticides used as toxic standards were chosen for this validation to represent two different modes of action: acute mortality of foragers and chronic brood effects. The ecotoxicological module was able to predict effect sizes in the tunnel studies based on information from standard laboratory tests. In conclusion, the BEEHAVEecotox model is an excellent tool to be used for honeybee risk assessment, interpretation of field and semifield studies, and exploring the efficiency of different mitigation measures. The principles for exposure and effect modules are portable and could be used for any well-constructed honeybee model. Environ Toxicol Chem 2022;41:2870-2882. © 2022 Bayer AG & Sygenta, et al. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Quality indicators of the atrial fibrillation management from the European (EORP) and Asia-Pacific (APHRS) registries

Abstract Background The 2020 ESC guideline for atrial fibrillation (AF) recommends universal quality indicators to identify areas for improvement in clinical practice. It also recommends using clinical registries to monitor clinical practice and identify areas for improvement. We have analysed two large comprehensive prospective clinical registries of patients with AF, the EURObservational Research Programme (EORP) and the Asia Pacific Heart Rhythm Society (APHRS), to compare the achievement of the ESC quality indicators in two major world populations. Methods The EORP and APHRS registries used the same electronic case report forms to collect data. T-test and Chi-squared test were used to compare registries. Logistic regression was used to identify pharmacological rate control therapy predictors in permanent AF. The model was adjusted for age, oral anticoagulation (OAC), EHRA and CHA2DS2-VASc scores, heart rate on the latest ECG and the region of recruitment (Europe or Asia) (STATA Corp, version 13). Results All 11096 EORP patients (59.3% males, age 69±11 years) and 5460 APHRS patients (66.3% males, age 68±12 years) had CHA2DS2-VASc and HAS-BLED scores documented at enrolment. The EORP register included a higher proportion of patients with CHA2DS2VASc ≥2 (81% vs 70%, p&amp;lt;0.001). These patients had similar OAC use (87%) in both registries, but NOAC use was higher in the APHRS (67% vs 34%, p&amp;lt;0.001), while dual antithrombotic use was more common in the EORP (14% vs 8%, p&amp;lt;0.001). The Table lists paraments that may impact OAC prescription. In patients with permanent AF, heart rate (82±20 vs 78±20, p&amp;lt;0.001) and antiarrhythmic pharmacotherapy (9% vs 5%) was higher in the EORP registry. On logistic regression, independent predictors of rate control with antiarrhythmic pharmacotherapy were higher EHRA 3 score (adjusted odds ratio (aOR) 1.8; 95% confidence interval (CI) 1.3–2.5, p&amp;lt;0.001); faster heart rate (aOR 1.01; 95% CI 1.00–1.02, p&amp;lt;0.001); younger age (aOR 0.97; 95% CI 0.96–0.98, p&amp;lt;0.001) and being recruited to the APHRS (aOR 0.56; 95% CI 0.40–0.79, p=0.001). APHRS vs EORP patients with non-permanent AF were less symptomatic (EHRA score I in 56% vs 38%) with less frequent use of antiarrhythmics (25% vs 37%), rhythm-management interventions (32% vs 46%), but higher use of catheter ablation (p&amp;lt;0.001 for all). Conclusion There are significant regional variations in achievement of the ESC quality indicator for AF. The variations may be due to differences in healthcare systems, but they may also reflect the population characteristics. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Since the start of EORP, the following companies have supported theprogramme: Abbott Vascular Int. (2011-2014), Amgen Cardiovascular(2009-2018), AstraZeneca (2014-2017), Bayer AG (2009-2018),Boehringer Ingelheim (2009-2019), Boston Scientific (2009-2012), TheBristol Myers Squibb and Pfizer Alliance (2011-2016), The Alliance DaiichiSankyo Europe GmbH and Eli Lilly and Company (2011-2017), Edwards(2016-2019), Gedeon Richter Plc. (2014-2017), Menarini Int. Op. (2009-2012), MSD-Merck &amp; Co. (2011-2014), Novartis Pharma AG (2014-2017), ResMed (2014-2016), Sanofi (2009-2011), and SERVIER (2009-2018).The Atrial Fibrillation NETwork (AFNET), conducting the registryin Germany, received support from The Bristol Myers Squibb/PfizerAlliance (2014-2018) and the German Centre for CardiovascularResearch (DZHK).

Geographic variation in heart failure with reduced ejection fraction: insights from the VICTORIA trial

Abstract Background Geographic differences and background therapy have not been explored in the global VICTORIA trial, which enrolled high-risk patients with recent worsening heart failure with reduced ejection fraction (HFrEF). Methods and results Among 5050 patients enrolled in 5 pre-specified geographic regions, 34% were from Eastern Europe, 18% Western Europe, 23% Asia Pacific, 14% Latin and South America, and 11% North America (Table 1). Patients from Western Europe were older, had more atrial fibrillation, and lower glomerular filtration rates. Patients from Eastern Europe had more coronary artery disease and exhibited more advanced symptoms (∼50% New York Heart Association [NYHA] class III), whereas those from Latin and South America were less symptomatic (∼70% NYHA class II). North American patients had the largest body mass index as well as more diabetes and hypertension. Levels of NT-proBNP at randomization and MAGGIC risk scores were highest in Western European patients. Evidence-based triple medication therapy was used most frequently in Latin and South America and less frequently in North America; conversely, cardiac resynchronization therapy and implantable cardioverter defibrillators were most frequently used in North America and least frequently in Latin and South America. The overall primary composite event rate (cardiovascular death or HF hospitalization) in the placebo arm was 36.6/100 person-years over a median of 10.8 months and after adjusting for the MAGGIC score. When examined by region, these event rates were nominally highest in North America and lowest in Western Europe. Conclusion Substantial regional differences exist in characteristics and treatments among patients in this global trial of patients with HFrEF and a recent worsening event. These findings demonstrate the continuing unmet needs and opportunities for enhancing care in HFrEF. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): VICTORIA was funded by Merck Sharp &amp; Dohme Corp., a subsidiary of Merck &amp; Co., Inc., Kenilworth, NJ, USA and Bayer AG, Wuppertal, Germany.

Longitudinal characterization of clinically relevant haemodynamics in conscious Ossabaw pigs with HFpEF

Abstract Background The constantly growing population of patients suffering from heart failure with preserved ejection fraction (HFpEF) is one of the largest unmet needs in cardiovascular medicine and translational animal models are important for identification and profiling of novel therapeutic approaches. Large animal models have shown that chronic cardiac pressure overload by aortic banding (AoB), when combined with a Western diet leads to left ventricular hypertrophy, diastolic dysfunction and metabolic syndrome in the Ossabaw pig, reflecting important features of human HFpEF characteristics. However, the requirement of invasive diagnostics under anaesthesia often limits the ability to monitor disease development continuously and compromises the results. Therefore, current disease models lack the temporal progression of clinically relevant HFpEF parameters like the left ventricular end diastolic pressure (LVEDP) and time constant of left ventricular relaxation (Tau). Purpose We aim to non-invasively investigate disease progression in Ossabaw pigs exhibiting a cardiometabolic HFpEF phenotype. The longitudinal assessment of LVEDP, Tau and heart rate (HR) should identify a time window to test novel therapeutics. Methods Naive, female Ossabaw pigs were instrumented with telemetric devices followed by AoB to induce chronic cardiac pressure overload. The wound healing and acclimatization period was followed by the start of a Western diet feeding regime to mimic components of the metabolic syndrome. Disease progression was characterized over 9 months by monthly telemetric recordings of LVEDP, Tau and HR and compared to a control (Ctrl) measurement in healthy animals. All animal studies followed the `Principles of laboratory animal care'. Results Compared to Ctrl the LVEDP is significantly elevated already 1 month (+8.90±0.4 mmHg) after AoB and further increases over time until 8 months (+18.80±0.4 mmHg) post AoB. Significant elevations in Tau are evident 4 months (+1.61±0.4 ms) post AoB. After 1 month the HR is significantly elevated (+13.90±0.7 bpm) but tends to normalize between 5 to 7 months post AoB. After AoB a maximal relative increase in LVEDP (+5.12±0.4 mmHg), Tau (+5.04±0.4 ms) and HR (+16.90±0.7 bpm) can be observed after 8 months. Conclusions We present long term haemodynamic changes over time in a translational in vivo model for HFpEF in Ossabaw pigs with high temporal resolution. For the first time elevations in key parameters allow to set a time point where HFpEF characteristics are evident, and a drug testing regime could be started. The opportunity to non-invasively and longitudinally follow on LVEDP, Tau and HR will be a clear benefit in the development of novel treatment options for HFpEF. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Bayer AG, Wuppertal

The complete bioavailability of asundexian is unaffected by tablet formulation, gastric pH or food

Abstract Background Anticoagulation and antiplatelet therapy, mainstays for the prevention of thromboembolic disorders, are associated with an increased bleeding risk. Asundexian, a novel, potent and reversible oral inhibitor of factor XIa, is independent of the extrinsic coagulation pathway and thus not expected to increase bleeding risk. Purpose To determine the absolute bioavailability (FAB), and to assess the impact of gastric pH modulators, tablet formulation, and food on the PK and safety of asundexian. Methods Four studies enrolled healthy White males aged 18–45 years. For FAB (20463), participants received a microdose of 50 μg stable [13C7,15N]-labelled asundexian intravenously (iv) 2 hours after 25 mg asundexian orally in the fasted state. The remaining studies randomized participants to each of 3 treatment sequences. Tablet formulation and food effects were explored in studies 19663 and 21660; participants received asundexian (immediate release [IR] vs amorphous solid dispersion [ASD] phase [Ph] 2 [19663] or ASD Ph 2 vs ASD Ph 3 [21660]) in the fasted states. Food effect was explored using the Ph 2 and Ph 3 tablets. Gastric pH modulators (omeprazole and antacid) were given with asundexian in the fasted state (20459). Blood samples were taken over 72–96 hours post dose. Key PK parameters were area under concentration/time curve (AUC; and AUC/dose [D]) and maximum observed concentration (Cmax; and Cmax/D). FAB was derived as (AUC/D)oral/(AUC/D)iv. Relative bioavailability (FR) was derived from the ratios (ASD Ph 2:IR or ASD Ph 3:ASD Ph 2) of AUC/D and Cmax/D (fasted); gastric pH modulation and food effect were derived from the ratios asundexian+pH modulator:asundexian and fed:fasted of AUC and Cmax, respectively. Results PK data were available for 59 participants. Asundexian was completely bioavailable (FAB, 103.9%). Ph 2 and Ph 3 ASD tablets exhibited a FR of 94.3% and 95.1% for AUC/D compared with the IR or Ph 2 ASD tablet, respectively. Cmax/D results were similar (95.5% and 88.7%, respectively). A high-calorie, high-fat meal reduced AUC and Cmax of asundexian to 91.1% and 78.3%, respectively (ASD Ph 2 tablet), and to 96.9% and 95.1%, respectively (ASD Ph 3 tablet). Coadministration of omeprazole had no influence on the PK of asundexian, whereas antacid slightly reduced AUC and Cmax by 10% and 16%, respectively. Geometric least-squares mean (90% confidence intervals) for the ratios of AUC(/D) and Cmax(/D) by treatment are shown in Figure 1. There were no serious adverse events (AEs) or deaths; most AEs were mild or moderate. Conclusions Orally administered asundexian was almost completely bioavailable. First pass metabolism in the gut and liver does not play an important role in the bioavailability of asundexian; there were no clinically relevant changes due to formulation, food conditions or gastric pH modulation. Results were used to guide dosing recommendations for subsequent Ph 2 (completed) and Ph 3 (planned) studies. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): BAYER AG

In patients with type 2 diabetes chronic kidney disease is a modifiable cardiovascular risk factor

Abstract Background/Introduction Chronic kidney disease (CKD) in patients with type 2 diabetes (T2D) is associated with an increased risk of cardiovascular (CV) events. The modifiability of CKD-associated CV risk in patients with T2D across a spectrum of CKD stages remains unknown. Purpose To test whether CKD, as defined jointly by estimated glomerular filtration rate (eGFR) and albuminuria (urine albumin-to-creatinine ratio [UACR]), is a modifiable CV risk factor in patients with T2D. Furthermore, to estimate the population-wide reduction in first CV events in the US if all eligible patients were treated with finerenone. Methods We estimated the incidence rates of CV events (composite of CV death, non-fatal stroke, non-fatal myocardial infarction, or hospitalisation for heart failure) over a median follow-up of 3.0 years in 13,026 patients with CKD and T2D, treated with finerenone or placebo, in a joint analysis by eGFR and UACR categories. Patients were from FIDELITY, a prespecified pooled analysis of two phase III trials, and had an eGFR ≥25 ml/min/1.73 m2 and UACR 30–5000 mg/g at screening.The potential impact of finerenone treatment on the US population was evaluated by simulating the number of first CV events that could be prevented per year with finerenone, using incidence rates from FIDELITY and prevalence rates of CKD in patients with T2D from the National Health and Nutrition Examination Survey (NHANES). Results Lower eGFR and higher UACR categories were associated with higher incidences of CV events in finerenone and placebo recipients (Figure). Finerenone reduced CV risk versus placebo (hazard ratio 0.86; 95% CI 0.78–0.95; p=0.0018) without evidence of moderation of risk reduction by combined eGFR and UACR categories (p interaction = 0.66; Figure 1). Using NHANES, a total of 6.4 million treatment-eligible individuals with CKD and T2D were identified; 75% had CKD with an eGFR ≥60 ml/min/1.73 m2 and 25% had CKD with an eGFR &amp;lt;60 ml/min/1.73 m2. Simulations using this NHANES population projected that 1 year of finerenone treatment could prevent 38,359 CV events in US patients with CKD and T2D, with 66% of events prevented in patients with eGFR ≥60 ml/min/1.73 m2. Conclusions Higher albuminuria and lower eGFR are associated with increased CV risk in patients with T2D. Across a range of eGFR and albuminuria categories, CV risk is modifiable. Therefore, CKD is a modifiable CV risk factor in part mediated by mineralocorticoid receptor overactivation. UACR screening to identify patients with T2D and albuminuria with an eGFR ≥60 ml/min/1.73 m2 is likely to provide a significant opportunity for population benefits. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Bayer AG