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Background and Aims: Hypertension has a high prevalence in heart failure with preserved ejection fraction (HFpEF), which can be controlled, uncontrolled, or even resistant. The effects of empagliflozin on systolic blood pressure (SBP), time in target range, incidence of hypertensive urgencies, and studied cardiovascular and renal outcomes in different hypertension categories and after treatment with empagliflozin in the EMPEROR-Preserved trial were explored., Methods: A total of 5533 patients were studied and the population was separated into resistant (resHTN), uncontrolled (uctrHTN), and controlled (ctrHTN) hypertension. The effect of SBP on outcomes and treatment effects of empagliflozin were explored. Analyses were done with Cox regression analyses adjusted for demographic and clinical confounders and with a mixed model for repeated measures., Results: Empagliflozin reduced SBP in resHTN slightly more than in the other categories in the first weeks, while thereafter there were no significant differences. The modest reduction in SBP resulted in a moderate increase in time at target and reduced hypertensive urgencies. The primary endpoint was more prevalent in resHTN (P = .0358), but the treatment effect of empagliflozin on the primary endpoint was similar in resHTN, uctrHTN, and ctrHTN (P for interaction = .92) as was the improvement of the estimated glomerular filtration rate slope (P for interaction = .95) and change in quality of life by empagliflozin., Conclusions: In HFpEF, the prevalence of resHTN is high and is associated with frequently higher outcome rates compared with ctrHTN and uctrHTN. The treatment effect was not modified by hypertension categories. This indicates that in HFpEF, moderate modifications of blood pressure do not affect overall outcomes and treatment effects of empagliflozin., (© The Author(s) 2025. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: In the EMPA-KIDNEY trial, empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, had positive cardiorenal effects in patients with chronic kidney disease who were at risk for disease progression. Post-trial follow-up was designed to assess how the effects of empagliflozin would evolve after the discontinuation of the trial drug., Methods: In the active trial, patients with chronic kidney disease were randomly assigned to receive either empagliflozin (10 mg once daily) or matching placebo and were followed for a median of 2 years. All the patients had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m 2 of body-surface area or an eGFR of at least 45 but less than 90 ml per minute per 1.73 m 2 with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Subsequently, surviving patients who consented were observed for 2 additional years. No trial empagliflozin or placebo was administered during the post-trial period, but local practitioners could prescribe open-label SGLT2 inhibitors, including open-label empagliflozin. The primary composite outcome was kidney disease progression or cardiovascular death as assessed from the start of the active-trial period to the end of the post-trial period., Results: Of the 6609 patients who had undergone randomization in the active trial, 4891 (74%) were enrolled in the post-trial period. During this period, the use of open-label SGLT2 inhibitors was similar in the two groups (43% in the empagliflozin group and 40% in the placebo group). During the combined active- and post-trial periods, a primary-outcome event occurred in 865 of 3304 patients (26.2%) in the empagliflozin group and in 1001 of 3305 patients (30.3%) in the placebo group (hazard ratio, 0.79; 95% confidence interval [CI], 0.72 to 0.87). During the post-trial period only, the hazard ratio for a primary-outcome event was 0.87 (95% CI, 0.76 to 0.99). During the combined periods, the risk of kidney disease progression was 23.5% in the empagliflozin group and 27.1% in the placebo group; the risk of the composite of death or end-stage kidney disease was 16.9% and 19.6%, respectively; and the risk of cardiovascular death was 3.8% and 4.9%, respectively. There was no effect of empagliflozin on death from noncardiovascular causes (5.3% in both groups)., Conclusions: In a broad range of patients with chronic kidney disease at risk for progression, empagliflozin continued to have additional cardiorenal benefits for up to 12 months after it was discontinued. (Funded by Boehringer Ingelheim and others; EMPA-KIDNEY ClinicalTrials.gov number, NCT03594110; EuDRACT number, 2017-002971-24.)., (Copyright © 2024 Massachusetts Medical Society.)

Background: There is limited published information on outcome adjudication in heart failure (HF) trials, particularly in heart failure with preserved ejection fraction (HFpEF)., Objectives: The study sought to compare investigator reports with clinical events committee (CEC) adjudication and assess the impact of the SCTI (Standardized Data Collection for Cardiovascular Trials) criteria., Methods: In the EMPEROR-Preserved (EMPagliflozin outcome tRial in Patients with chronic heart Failure With Preserved Ejection Fraction) trial, we compared investigator reports with CEC for concordance, treatment effect on primary composite outcome events and components (first event primary heart failure hospitalization [HHF] or cardiovascular [CV] mortality), prognosis after first HHF, total HHF, and trial duration with and without SCTI criteria., Results: The CEC confirmed 67.4% investigator-reported events for the primary outcome (CV mortality 82.7%, HHF 66.3%). The HR for treatment effect did not differ between adjudication methods for the primary outcome: investigator reports (HR: 0.77; 95% CI: 0.69-0.87), CEC (HR: 0.79; 95% CI: 0.69-0.90), its components, or total HHFs. The prognosis after the first HHF for all-cause mortality and CV mortality also did not differ between investigator reports and the CEC, nor did investigator reports and HHFs with a different CEC cause. SCTI criteria were present in 92% of CEC HHFs with a similar treatment effect to non-SCTI criteria. The investigator-reported primary events reached the protocol target number 6 months earlier than the CEC (7 months with full SCTI criteria)., Conclusions: Investigator adjudication is an alternative to a CEC with similar accuracy and faster event accumulation in HFpEF. The use of granular (SCTI) criteria did not improve trial performance. Our data suggest that a broader definition of an HHF event could be particularly beneficial in HFpEF clinical trials. (EMPagliflozin outcome tRial in Patients with chronic heart Failure With Preserved Ejection Fraction; NCT03057951)., Competing Interests: Funding Support and Author Disclosures The EMPEROR-Preserved trial was funded by the Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance. Dr Carson has received consulting fees from Boehringer Ingelheim and IQVIA related to work on a clinical events committee during the conduct of the study. Dr Teerlink has received research support from and/or served as a consultant for Amgen, AstraZeneca, Bayer AG, Boehringer Ingelheim, Bristol Myers Squibb, Cytokinetics, Medtronic, Merck, Novartis, Servier, and Windtree Therapeutics. Dr Komajda has received consulting fees from Boehringer Ingelheim related to work on a clinical events committee during the conduct of the study; and personal fees from Novartis, Servier, Amgen, Sanofi, Bayer, AstraZeneca, Lilly, and Torrent. Dr Anand has received consulting fees from Boehringer Ingelheim related to work on a clinical events committee during the conduct of the study; and personal fees from Novartis, Servier, Amgen, Sanofi, Bayer, AstraZeneca, Lilly, and Torrent. Dr Packer has received consulting fees from AbbVie, Actavis, Amgen, Amarin, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Casana, CSL Behring, Cytokinetics, Johnson and Johnson, Eli Lilly and Company, Moderna, Novartis, ParatusRx, Pfizer, Relypsa, Salamandra, Synthetic Biologics, and Theravance; and served on the Trial Executive Committee for the Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance (trial sponsor). Dr Butler has received consulting fees from Boehringer Ingelheim, Cardior, CVRx, Foundry, G3 Pharma, Imbria, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, Novo Nordisk, Relypsa, Roche, Sanofi, Sequana Medical, VWave, and Vifor; and served on the Trial Executive Committee for the Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance (trial sponsor). Dr Doehner has received consulting fees from Boehringer Ingelheim related to work on the clinical events committee during the conduct of the study; personal fees from Aimediq, Bayer, Boehringer Ingelheim, Medtronic, Pfizer, Sanofi, Sphingotec, and Vifor Pharma; and research support from the European Union (Horizon2020), the German Ministry of Education and Research, the German Center for Cardiovascular Research, Vifor Pharma, and ZS Pharma. Dr Ferreira has received consulting fees from Boehringer Ingelheim; and served on the Trial Executive Committee for the Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance (trial sponsor). Dr Filippatos has received lecture fees from and/or committee member contributions from clinical trials sponsored by Bayer, Medtronic, Vifor, Servier, Novartis, and Amgen; research support from the European Union; and served on the Trial Executive Committee for the Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance (trial sponsor). Dr Haass has received consulting fees from Boehringer Ingelheim related to work on the clinical events committee during the conduct of the study. Dr Miller has received consulting fees from Abbott, Boehringer Ingelheim, Respicardia, CVRx, Pfizer, and AbbVie. Dr Pehrson has received consulting fees and/or lecture fees from Boehringer Ingelheim, GlaxoSmithKline, Celgene, Bristol Myers Squibb, Bayer, and Johnson and Johnson. Dr Pocock has received consulting fees and payment or honoraria for lectures, presentations, Speakers Bureau service, manuscript writing, or educational events from Boehringer Ingelheim; and served on the Trial Executive Committee for the Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance (trial sponsor). Drs Iwata, Brueckmann, and Gasior are employees of Boehringer Ingelheim. Dr Zannad has received steering committee or advisory board fees from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cardior, CVRx, Janssen, Livanova, Merck, Mundipharma, Novartis, Novo Nordisk, and Vifor Fresenius; and served on the Trial Executive Committee for the Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance (trial sponsor). Dr Anker has received grants and personal fees from Vifor International and Abbott Vascular; personal fees from AstraZeneca, Bayer, Brahms, Boehringer Ingelheim, Cardiac Dimensions, Novartis, Occlutech, Servier, and Vifor International; and served on the Trial Executive Committee for the Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance (trial sponsor)., (Copyright © 2025 American College of Cardiology Foundation. All rights reserved.)

Objective: The objective of this study was to describe the rationale and design of two multinational phase 3 clinical trials of survodutide, an investigational glucagon and glucagon-like peptide-1 receptor dual agonist for the treatment of obesity with or without type 2 diabetes (T2D; SYNCHRONIZE-1 and -2)., Methods: In these ongoing double-blind trials, participants were randomized to once-weekly subcutaneous injections of survodutide or placebo added to lifestyle modification. Survodutide doses are uptitrated to 3.6 or 6.0 mg, and dose flexibility is permitted. Participants (n = 726) in SYNCHRONIZE-1 (NCT06066515) have a baseline BMI ≥ 30 kg/m 2 or ≥27 kg/m 2 with at least one obesity-related complication but without T2D; participants (n = 755) in SYNCHRONIZE-2 (NCT06066528) have a baseline BMI ≥ 27 kg/m 2 and T2D. The primary endpoints are percentage change in body weight and proportion of participants achieving ≥5% body weight reduction from baseline to week 76. Secondary endpoints include change in systolic blood pressure and measures of glycemia. A SYNCHRONIZE-1 substudy is evaluating changes in body composition and liver fat content using magnetic resonance imaging., Conclusions: These trials are designed to provide robust evaluation of the efficacy, safety, and tolerability of survodutide for the treatment of obesity in the presence or absence of T2D., (© 2024 The Author(s). Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)