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OBJECTIVE Finerenone reduced the risk of kidney and cardiovascular events in people with chronic kidney disease (CKD) and type 2 diabetes in the FIDELIO-DKD (NCT02540993) and FIGARO-DKD (NCT02545049) phase 3 studies. Effects of finerenone on outcomes in patients taking sodium–glucose cotransporter 2 inhibitors (SGLT2is) were evaluated in a prespecified pooled analysis of these studies. RESEARCH DESIGN AND METHODS Patients with type 2 diabetes and urine albumin-to-creatinine ratio (UACR) ≥30–≤5,000 mg/g and estimated glomerular filtration rate (eGFR) ≥25 mL/min/1.73 m2 were randomized to finerenone or placebo; SGLT2is were permitted at any time. Outcomes included cardiovascular composite (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) and kidney composite end points (kidney failure, sustained ≥57% eGFR decline, or renal death), changes in UACR and eGFR, and safety outcomes. RESULTS Among 13,026 patients, 877 (6.7%) received an SGLT2i at baseline and 1,113 (8.5%) initiated one during the trial. For the cardiovascular composite, the hazard ratios (HRs) were 0.87 (95% CI 0.79–0.96) without SGLT2i and 0.67 (95% CI 0.42–1.07) with SGLT2i. For the kidney composite, the HRs were 0.80 (95% CI 0.69–0.92) without SGLT2i and 0.42 (95% CI 0.16–1.08) with SGLT2i. Baseline SGLT2i use did not affect risk reduction for the cardiovascular or kidney composites with finerenone (Pinteraction = 0.46 and 0.29, respectively); neither did SGLT2i use concomitant with study treatment. CONCLUSIONS Benefits of finerenone compared with placebo on cardiorenal outcomes in patients with CKD and type 2 diabetes were observed irrespective of SGLT2i use.

Finerenone is a potent and selective mineralocorticoid receptor (MR) antagonist that slowed progression of CKD and reduced risk of CV outcomes vs. placebo in patients with CKD and T2D in the FIDELIO-DKD and FIGARO-DKD phase 3 trials. MR overactivation is involved in DR pathogenesis. To evaluate potential benefits of oral finerenone on progression of DR, two studies of identical observational design (ReFineDR and DeFineDR) retrospectively collected data from patients with DR in FIDELIO-DKD/FIGARO-DKD at selected centers. Eligible patients had a routine ophthalmological examination showing NPDR in ≥1 eye performed 6 months prior to 1 month post-randomization in FIDELIO-DKD/FIGARO-DKD, and ≥1 subsequent ophthalmological assessment. Patients with advanced DR were excluded; inclusion was blinded to FIDELIO-DKD/FIGARO-DKD treatment assignment. Primary endpoint was occurrence of vision-threatening events (ASN, DME or PDR) at 2 years. Overall, 134 patients received finerenone and 1received placebo, of whom 68.7% and 71.8% had mild/moderate NPDR, 3.0% and 10.0% had severe NPDR, 27.6% and 15.5% had NPDR of unknown severity and 70.1% and 64.5% had HbA1c >7.5%, at baseline (mean HbA1c 8.25 [SD 1.41] and 8.18 [SD 1.34]) . At 2 years, 5 (3.7%) and 7 (6.4%) patients in the finerenone and placebo groups had a vision-threatening event in ≥1 eye (difference -0.026, 95% CI -0.082 to 0.029, p=0.3550) . The number of events increased after 2 years, with trends in Kaplan-Meier estimated cumulative incidence probabilities in favor of finerenone at 30 and 36 months (post hoc) . Results were generally consistent across components of the primary endpoint and subgroups with baseline HbA1c ≤ and >7.5%, UACR 30- Disclosure P.Rossing: Consultant; Astellas Pharma Inc., AstraZeneca, Bayer AG, Gilead Sciences, Inc., Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi, Speaker's Bureau; Eli Lilly and Company. D.Finis: Employee; Bayer AG. S.Leal: Employee; Bayer Consumer Care AG. T.Schmelter: Employee; Bayer AG, Stock/Shareholder; Bayer AG. G.Bakris: Consultant; Alnylam Pharmaceuticals, Inc., AstraZeneca, DiaMedica Therapeutics, Inc., Horizon Therapeutics plc, Ionis Pharmaceuticals, Merck & Co., Inc., Other Relationship; Novo Nordisk. S.Anker: Consultant; Bayer AG, Boehringer Ingelheim International GmbH, Novartis AG, Novo Nordisk, Vifor Pharma Management Ltd., Research Support; Abbott. J.G.Garweg: Advisory Panel; AbbVie Inc., Research Support; Roche Pharmaceuticals, Speaker's Bureau; Bayer AG, Novartis AG. T.Osonoi: Research Support; Bayer AG, Eli Lilly and Company, Gilead Sciences, Inc., Kowa Company, Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Speaker's Bureau; Novo Nordisk. B.Pitt: Advisory Panel; Merck & Co., Inc., Consultant; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Lexicon Pharmaceuticals, Inc., Vifor Pharma Management Ltd. S.Rosas: Advisory Panel; AstraZeneca, Teladoc Health, Other Relationship; Bayer AG, Research Support; AstraZeneca, Bayer AG. L.M.Ruilope: Consultant; Bayer AG. D.Zhu: n/a. M.Brinker: Employee; Bayer AG.

Introduction: Finerenone reduced the risk of cardiovascular (CV) and kidney outcomes, without affecting HbA1c, in CKD and T2D patients in the FIDELITY prespecified pooled analysis of the FIDELIO-DKD and FIGARO-DKD studies. Here, we evaluate the effect of finerenone by baseline HbA1c, HbA1c variability, and diabetes duration. Methods: Patients with T2D and CKD (UACR ≥30-≤5000 mg/g and eGFR ≥25 mL/min/1.73 m2) were randomized to finerenone or placebo. Effects of finerenone vs. placebo on CV (CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) and kidney (kidney failure, sustained ≥57% eGFR decline from baseline, or renal death) composite outcomes were analyzed by baseline HbA1c quartiles, HbA1c variability (first year of treatment) , and diabetes duration quartiles. Results: In 13,026 patients included in the analysis, mean baseline HbA1c was 7.7% and diabetes duration was 15.4 years. Higher baseline HbA1c quartiles had longer diabetes duration and more diabetes-related complications. Risk reductions in the CV and kidney composite outcomes with finerenone vs. placebo were consistent across HbA1c (p-interaction 0.52 and 0.09, respectively) and diabetes duration (p-interaction 0.12 and 0.75) quartiles. HbA1c variability in the first year of treatment was associated with higher cardiorenal risks; each 1 unit increase in mean absolute residual of HbA1c was associated with a 20% increased risk of a CV event (HR 1.20; 95% CI 1.07-1.35; p=0.0016) and a 36% increased risk of a kidney event (HR 1.36; 95% CI 1.21-1.52; p Conclusion: Greater variability in HbA1c was associated with increased risks of cardiorenal outcomes. Risk reductions in the CV and kidney outcomes with finerenone in patients with CKD and T2D were not modified by baseline HbA1c, HbA1c variability, or duration of diabetes. Disclosure J. B. Mcgill: Advisory Panel; Gilead Sciences, Inc., Lilly Diabetes, MannKind Corporation, Novo Nordisk A/S, Provention Bio, Inc., Salix Pharmaceuticals, Consultant; Bayer AG, Boehringer Ingelheim International GmbH, Research Support; Dexcom, Inc., Novo Nordisk. M. Brinker: Employee; Bayer AG. A. Joseph: Employee; Bayer AG. A. Z. Lage: None. R. Lawatscheck: None. C. Scott: Employee; Bayer AG. P. Rossing: Consultant; Astellas Pharma Inc., AstraZeneca, Bayer AG, Gilead Sciences, Inc., Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi, Speaker’s Bureau; Eli Lilly and Company. R. Agarwal: Advisory Panel; Akebia Therapeutics, Inc., Bayer AG, Board Member; Chinook Therapeutics Inc., DiaMedica Therapeutics, Inc., Vertex Pharmaceuticals Incorporated, Consultant; Boehringer Ingelheim International GmbH, Reata Pharmaceuticals, Inc., Vifor Pharma Management Ltd. S. Anker: Consultant; Bayer AG, Boehringer Ingelheim International GmbH, Novartis AG, Novo Nordisk, Vifor Pharma Management Ltd., Research Support; Abbott. G. Bakris: Consultant; Alnylam Pharmaceuticals, Inc., AstraZeneca, DiaMedica Therapeutics, Inc., Horizon Therapeutics plc, Ionis Pharmaceuticals, Merck & Co., Inc., Other Relationship; Novo Nordisk. G. Filippatos: Other Relationship; Amgen Inc., Amgen Inc., Bayer AG, Boehringer Ingelheim International GmbH, Medtronic, Novartis AG, Servier Laboratories, Vifor Pharma Management Ltd. B. Pitt: Advisory Panel; Merck & Co., Inc., Consultant; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Lexicon Pharmaceuticals, Inc., Vifor Pharma Management Ltd. L. M. Ruilope: Consultant; Bayer AG. A. L. Birkenfeld: None. L. Caramori: Advisory Panel; Bayer AG, Consultant; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk, Research Support; Bayer AG, Novartis AG.

Introduction: Finerenone reduced risk of cardiorenal outcomes in patients with CKD and T2D in the FIDELIO-DKD and FIGARO-DKD studies. In FIDELIO-DKD the effects of finerenone on kidney and CV outcomes were consistent irrespective of glucagon-like peptide-1 receptor agonist (GLP-1RA) use, but analyses were better powered to evaluate change in urine albumin-to-creatinine ratio (UACR) . Here, we extend these analyses to patients in both studies (FIDELITY analysis) , thus encompassing a larger population with broader inclusion criteria. Methods: Patients with T2D and CKD (UACR ≥30- Results: Of 13026 patients, 944 (7.2%) received GLP-1RAs at baseline. Results were consistent irrespective of GLP-1RA use at baseline for the CV composite outcome (hazard ratio [HR] 0.76; 95% CI 0.52-1.with GLP-1RA; HR 0.87, 95% CI 0.79-0.96 without GLP-1RA; p-interaction 0.63) , and the kidney composite outcome (HR 0.82; 95% CI 0.45-1.48 with GLP-1RA; HR 0.77, 95% CI 0.67-0.89 without GLP-1RA; p-interaction 0.79) . A greater reduction in UACR was observed with finerenone in patients taking GLP-1RA at baseline (placebo-corrected change -38% with GLP-1RA and -31% without GLP-1RA use; p-interaction 0.03) . Incidence of hyperkalemia was similarly increased with finerenone irrespective of GLP-1RA use at baseline. Conclusion: The benefits of finerenone on composite CV and kidney outcomes in patients with CKD and T2D are not modified by GLP-1RA use at baseline, with an increased effect observed for UACR reduction, suggesting a different mechanism of reduction in albuminuria. Disclosure P.Rossing: Consultant; Astellas Pharma Inc., AstraZeneca, Bayer AG, Gilead Sciences, Inc., Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi, Speaker's Bureau; Eli Lilly and Company. P.Viswanathan: Employee; Bayer AG. R.Lawatscheck: None. A.Joseph: Employee; Bayer AG. G.Bakris: Consultant; Alnylam Pharmaceuticals, Inc., AstraZeneca, DiaMedica Therapeutics, Inc., Horizon Therapeutics plc, Ionis Pharmaceuticals, Merck & Co., Inc., Other Relationship; Novo Nordisk. S.Anker: Consultant; Bayer AG, Boehringer Ingelheim International GmbH, Novartis AG, Novo Nordisk, Vifor Pharma Management Ltd., Research Support; Abbott. G.Filippatos: Other Relationship; Amgen Inc., Amgen Inc., Bayer AG, Boehringer Ingelheim International GmbH, Medtronic, Novartis AG, Servier Laboratories, Vifor Pharma Management Ltd. B.Pitt: Advisory Panel; Merck & Co., Inc., Consultant; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Lexicon Pharmaceuticals, Inc., Vifor Pharma Management Ltd. L.M.Ruilope: Consultant; Bayer AG. V.Fonseca: Consultant; Abbott, Asahi Kasei Corporation, Bayer AG, Novo Nordisk, Sanofi, Research Support; Fractyl Health, Inc., Jaguar Gene Therapy, Stock/Shareholder; Abbott, Amgen Inc., BRAVO4Health, Mellitus Health. G.E.Umpierrez: Research Support; AstraZeneca, Dexcom, Inc., Novo Nordisk. L.Caramori: Advisory Panel; Bayer AG, Consultant; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk, Research Support; Bayer AG, Novartis AG. M.Lambelet: Other Relationship; Bayer AG.

Objective: Finerenone significantly improved cardiorenal outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) in FIDELIO-DKD. We explored whether baseline HbA1c and insulin treatment influenced outcomes. Research design and methods: Patients with T2D, urine albumin-to-creatinine ratio (UACR) 30–5,000 mg/g, estimated glomerular filtration rate (eGFR) 25–2, and treated with optimized renin–angiotensin system blockade were randomized to finerenone or placebo. Efficacy outcomes included kidney (kidney failure, sustained decrease ≥40% in eGFR from baseline, or renal death) and cardiovascular (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) composite endpoints. Patients were analyzed by baseline insulin use and by baseline HbA1c Results: Of 5,674 patients, 3,637 (64.1%) received insulin at baseline. Overall, 5,663 patients were included in the analysis for HbA1c; 2,794 (49.3%) had baseline HbA1c 1c and insulin use (Pinteraction 0.41 and 0.56, respectively). Cardiovascular composite outcome incidence was reduced with finerenone irrespective of baseline HbA1c and insulin use (Pinteraction 0.70 and 0.33, respectively). Although baseline HbA1c did not affect kidney event risk, cardiovascular risk increased with higher HbA1c. UACR reduction was consistent across subgroups. Adverse events were similar between groups regardless of baseline HbA1c level and insulin use; few finerenone-treated patients discontinued treatment due to hyperkalemia. Conclusion: Finerenone reduces kidney and cardiovascular outcome risk in patients with CKD and T2D and risks appear consistent irrespective of HbA1c levels or insulin use.

Introduction: Finerenone is a novel, selective, nonsteroidal mineralocorticoid receptor antagonist that significantly reduced the risk of kidney and CV outcomes in patients with CKD and T2D in the FIDELIO-DKD trial, with no effect on blood glucose. In advanced T2D, insulin is often used to control glycemia. This analysis will report outcomes from the FIDELIO-DKD trial by baseline insulin treatment. Methods: In FIDELIO-DKD (NCT02540993), 5734 patients with T2D, UACR 30-5000 mg/g, eGFR 25- Results: Of the 5674 patients analyzed, 3637 (64.1%) were treated with insulin or insulin analogues at baseline. Patients treated with insulin at baseline had a higher A1C and a longer duration of diabetes, with higher proportions of statin and GLP-1RA use, and lower use of other anti-hyperglycemic agents than those who were not. Finerenone did not affect A1C during the trial. The primary and key secondary CV outcome occurred in fewer patients treated with finerenone, with no between-group interaction (primary outcome: HR 0.85, 95% CI 0.73-0.98 with insulin; HR 0.79, 95% CI 0.64-0.96 without insulin; P-value for interaction 0.56; CV outcome: HR 0.82, 95% CI 0.69-0.97 with insulin; HR 0.95, 95% CI 0.74-1.23 without insulin; P-value for interaction 0.33). Hyperkalemia events were similar between groups (mean treatment difference between finerenone and placebo for treatment-emergent serum potassium >5.5 mmol/L, 11.1% with insulin and 13.4% without insulin), with a low incidence of hyperkalemia-related treatment discontinuation. Conclusion: Finerenone has a beneficial effect on kidney and CV outcomes in patients with CKD and T2D, irrespective of insulin use at baseline. Disclosure P. Rossing: Advisory Panel; Self; Astellas Pharma Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., Merck KGaA, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi, Vifor Pharma Management Ltd. L. Roessig: Employee; Self; Bayer AG. C. Scott: Employee; Self; Bayer PLC. G. Bakris: Consultant; Self; Alnylam Pharmaceuticals, Inc., Bayer AG, Ionis Pharmaceuticals, Merck & Co., Inc., Vascular Dynamics Inc. R. Agarwal: Advisory Panel; Self; Akebia Therapeutics, Inc., Bayer Healthcare Pharmaceuticals Inc., Diamedica, Relypsa Inc., Sanofi US, Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Reata Pharmaceuticals, Inc., Other Relationship; Self; AstraZeneca, Chinook. S. Anker: Consultant; Self; Abbott, Bayer AG, Boehringer Ingelheim International GmbH, Cardiac Dimensions Pty. Ltd., Impulse Dynamics, Novartis AG, Servier Laboratories, Vifor Pharma Management Ltd., Other Relationship; Self; Abbott, Vifor Pharma Management Ltd. G. Filippatos: Other Relationship; Self; Bayer AG, Boehringer Ingelheim International GmbH, Servier Laboratories. B. Pitt: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Consultant; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Lexicon Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Sanofi. L. M. Ruilope: None. R. Macisaac: Advisory Panel; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Novo Nordisk, Servier Laboratories, Speaker’s Bureau; Self; Boehringer Ingelheim International GmbH, Novo Nordisk. J. Wainstein: Board Member; Self; Novo Nordisk, Research Support; Self; Bayer Healthcare Pharmaceuticals Inc., Kowa Company, Ltd., Speaker’s Bureau; Self; Novo Nordisk. A. Joseph: Employee; Self; Bayer AG. Funding Bayer AG

Introduction: Finerenone is a novel, selective, nonsteroidal mineralocorticoid receptor antagonist that significantly reduced the risk of kidney and CV outcomes in patients with CKD and T2D in the FIDELIO-DKD trial. GLP-1RAs have also been shown to improve CV outcomes in patients with T2D as well as lowering albuminuria. The mechanism of action of finerenone and GLP-1RAs are largely independent but their combined effects are unknown. This analysis will report outcomes from the FIDELIO-DKD trial in patients by GLP-1RA treatment. Methods: FIDELIO-DKD (NCT02540993) randomized 5734 patients to oral finerenone or placebo. Patients with T2D, UACR 30-5000mg/g and eGFR 25- Results: Of the 5674 patients analyzed, 394 (6.9%) were treated with a GLP-1RA at baseline. Patients treated with GLP-1RAs at baseline had a higher BMI and A1C, with higher diuretic and statin use, lower median UACR and less presence of CVD than those who were not. There was no between-group interaction for the primary kidney (HR 1.17, 95% CI 0.71-1.90 with GLP-1RA; HR 0.80, 95% CI 0.71-0.91 without GLP-1RA; P-interaction 0.15) or secondary CV outcomes (HR 1.02, 95% CI 0.60-1.74 with GLP-1RA; HR 0.85, 95% CI 0.73-0.98 without GLP-1RA; P-interaction 0.51). The reduction in UACR was independent of GLP-1RA use (ratio of LS-means 0.63, 95% CI 0.56-0.70 with GLP-1RA; 0.69, 95% CI 0.67-0.72 without GLP-1RA; P-interaction 0.20). Overall, incidences of hyperkalemia events were similar in patients with and without GLP-1RA use. Conclusion: The effects of finerenone on kidney and CV outcomes appear consistent irrespective of GLP-1RA use, with a potential additive benefit for UACR reduction. Disclosure P. Rossing: Advisory Panel; Self; Astellas Pharma Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., Merck KGaA, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi, Vifor Pharma Management Ltd. A. Z. Lage: Employee; Self; Bayer Healthcare Pharmaceuticals Inc. C. Scott: Employee; Self; Bayer PLC. G. Bakris: Consultant; Self; Alnylam Pharmaceuticals, Inc., Bayer AG, Ionis Pharmaceuticals, Merck & Co., Inc., Vascular Dynamics Inc. R. Agarwal: Advisory Panel; Self; Akebia Therapeutics, Inc., Bayer Healthcare Pharmaceuticals Inc., Diamedica, Relypsa Inc., Sanofi US, Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Reata Pharmaceuticals, Inc., Other Relationship; Self; AstraZeneca, Chinook. S. Anker: Consultant; Self; Abbott, Bayer AG, Boehringer Ingelheim International GmbH, Cardiac Dimensions Pty. Ltd., Impulse Dynamics, Novartis AG, Servier Laboratories, Vifor Pharma Management Ltd., Other Relationship; Self; Abbott, Vifor Pharma Management Ltd. G. Filippatos: Other Relationship; Self; Bayer AG, Boehringer Ingelheim International GmbH, Servier Laboratories. B. Pitt: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Consultant; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Lexicon Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Sanofi. L. M. Ruilope: None. A. Amod: Advisory Panel; Self; Aspen South Africa, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Servier Laboratories, Consultant; Self; Servier Laboratories, Other Relationship; Self; Bayer AG, Merck Sharp & Dohme Corp., Novo Nordisk, Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Sanofi, Servier Laboratories. M. Marre: Board Member; Self; Merck Sharp & Dohme Corp., Consultant; Self; Novo Nordisk. A. Joseph: Employee; Self; Bayer AG. Funding Bayer AG

Introduction: Patients with CKD and T2D are at high risk of morbidity and mortality despite the use of guideline-directed therapies. Finerenone, a novel, selective, nonsteroidal mineralocorticoid receptor antagonist, reduced the risk of adverse kidney and CV outcomes in patients with CKD and T2D; here we report outcomes by baseline A1C. Methods: FIDELIO-DKD (NCT02540993) randomized 5734 patients from 48 countries to receive oral finerenone or placebo. Eligible patients had T2D, with a UACR of ≥30-≤5000 mg/g, eGFR ≥25‍-‍12% at screening were excluded. The primary outcome was a composite of kidney failure, sustained ≥40% decrease in eGFR from baseline, or renal death. The key secondary outcome was a composite of CV death, non-fatal MI, non-fatal stroke, or hospitalization for HF. Results: In the 5674 patients analyzed, the mean baseline A1C was 7.7% and mean diabetes duration was 16.6 years; finerenone did not affect A1C during the trial. Overall, 2948 patients had A1C ≤7.5% and 2715 patients had A1C >7.5% at baseline. Patients with higher A1C levels were more likely to use insulin and had a longer duration of diabetes. After a median follow-up of 2.6 years, the primary outcome occurred in fewer patients treated with finerenone compared with placebo, this was observed in both the A1C ≤7.5% and >7.5% groups (18.7% vs. 21.5% patients with A1C of ≤7.5% [HR 0.86; 95% CI 0.73-1.01]; 16.9% vs. 20.7% patients with A1C >7.5% [HR 0.79; 95% CI 0.66-0.94]; P-interaction 0.47). Finerenone also reduced the incidence of the key secondary CV outcome compared with placebo regardless of baseline A1C (HR 0.88; 95% CI 0.71-1.07 for A1C ≤7.5% and HR 0.83; 95% CI 0.69-1.01 for A1C >7.5%; P-interaction 0.73). Reduction in UACR was consistent across subgroups. Overall, hyperkalemia events were independent of A1C level. Conclusion: In patients with CKD and T2D, treatment with finerenone reduced the risk for developing adverse kidney and CV outcomes independent of baseline A1C. Disclosure P. Rossing: Advisory Panel; Self; Astellas Pharma Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., Merck KGaA, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi, Vifor Pharma Management Ltd. M. Brinker: Employee; Self; Bayer AG, Stock/Shareholder; Self; Bayer AG. C. Scott: Employee; Self; Bayer PLC. G. Bakris: Consultant; Self; Alnylam Pharmaceuticals, Inc., Bayer AG, Ionis Pharmaceuticals, Merck & Co., Inc., Vascular Dynamics Inc. E. Burgess: Advisory Panel; Self; Bayer Inc. R. Agarwal: Advisory Panel; Self; Akebia Therapeutics, Inc., Bayer Healthcare Pharmaceuticals Inc., Diamedica, Relypsa Inc., Sanofi US, Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Reata Pharmaceuticals, Inc., Other Relationship; Self; AstraZeneca, Chinook. S. Anker: Consultant; Self; Abbott, Bayer AG, Boehringer Ingelheim International GmbH, Cardiac Dimensions Pty. Ltd., Impulse Dynamics, Novartis AG, Servier Laboratories, Vifor Pharma Management Ltd., Other Relationship; Self; Abbott, Vifor Pharma Management Ltd. G. Filippatos: Other Relationship; Self; Bayer AG, Boehringer Ingelheim International GmbH, Servier Laboratories. B. Pitt: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Consultant; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Lexicon Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Sanofi. L. M. Ruilope: None. P. Gillard: None. A. Joseph: Employee; Self; Bayer AG. Funding Bayer AG

This is an author-created, uncopyedited electronic version of an article accepted for publication in Diabetes Care. The American Diabetes Association (ADA), publisher of Diabetes Care, is not responsible for any errors or omissions in this version of the manuscript or any version derived from it by third parties. The definitive publisher-authenticated version will be available in a future issue of Diabetes Care 39.10 (2016): 1729-1737 in print and online at http://care.diabetesjournals.org, Nighttime blood pressure (BP) and albuminuria are two important and independent predictors of cardiovascularmorbidity andmortality. Here, we examined the quantitative differences in nighttime systolic BP (SBP) across albuminuria levels in patients with and without diabetes and chronic kidney disease. RESEARCH DESIGN AND METHODS A total of 16,546 patients from the Spanish Ambulatory Blood Pressure Monitoring Registry cohort (mean age 59.6 years, 54.9% men) were analyzed. Patients were classified according to estimated glomerular filtration rate (eGFR), as ≥60 or 300 mg/g). Office and 24-h BP were determined with standardized methods and conditions. RESULTS High albuminuria was associated with a statistically significant and clinically substantial higher nighttime SBP (6.8 mmHg higher than with normoalbuminuria, P < 0.001). This association was particularly striking at very high albuminuria among patients with diabetes and low eGFR (16.5 mmHg, P < 0.001). Generalized linear models showed that after full adjustment for demographic, lifestyles, and clinical characteristics, nighttime SBP was 4.8 mmHg higher in patients with high albuminuria than in those with normoalbuminuria (P < 0.001), and patients with very high albuminuria had a 6.1 mmHg greater nighttime SBP than those with high albuminuria (P < 0.001). These differences were 3.8 and 3.1 mmHg, respectively, among patients without diabetes, and 6.5 and 8 mmHg among patients with diabetes (P < 0.001). CONCLUSIONS Albuminuria in hypertensive patients is accompanied by quantitatively striking higher nighttime SBP, particularly in those with diabetes with very high albuminuria and low eGFR, Specific funding for this study analysis was obtained from FIS grants PI10/01011 PI11/02432, PI13/02321, PIE13/00045, PI14/01841, CP15/0129, and also from Fundación SENEFRO, Fondos FEDER, and by Cátedra UAM de Epidemiología y Control del Riesgo Cardiovascular

In 2003, the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VII) published its ultimate guidelines for hypertension prevention and management (1). One of the key messages was the definition of a new category of blood pressure (BP) levels, i.e., prehypertension, that included individuals with a systolic BP of 120–139 mmHg or a diastolic BP of 80–89 mmHg. Patients with prehypertension were considered at increased risk for progression to hypertension and individuals in the 130/80 to 139/89 mmHg range were at twice the risk of developing hypertension than subjects with lower values (2). In the same year, the European Society of Hypertension and the European Society of Cardiology (ESH-ESC) published their guidelines for the management of arterial hypertension and, for the same range of BP, two different categories of BP were defined: normal BP (systolic BP of 120–129 mmHg, or diastolic BP of 80–84 mmHg) and high-normal BP (systolic BP of 130–139 mmHg, or diastolic BP of 85–89 mmHg) (3). In 2007, the ESH-ESC committee decided against using the term “prehypertension” for several reasons (4). First, even in the Framingham study, the risk of developing hypertension was definitely higher in subjects with high-normal BP than in patients with normal BP (2,5), and therefore there is little reason to combine the two groups. Second, given the ominous significance of the word “hypertension” for the layman, the term “prehypertension” may, in many subjects, create anxiety and a request for unnecessary medical visits and examinations. Finally, although lifestyle changes recommended by the 2003 JNC VII guidelines for all prehypertensive individuals may be a valuable population strategy (1), in practice, this category is a highly differentiated one, with the extremes consisting of subjects with no need of any intervention (e.g., an …