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In-hospital and long-term outcomes after coronary angioplasty in 28 dialysis diabetic and 84 dialysis nondiabetic patients were compared with clinical outcomes after coronary angioplasty in 28 nondialysis diabetic and 84 nondialysis, nondiabetic patients matched according to clinical and angiographic characteristics. The rate of angiographic success in diabetic dialysis patients was high and similar in the 4 groups. The risk of 4-year cardiac death and nonfatal myocardial infarction was higher in dialysis diabetics than in dialysis nondiabetics (odds ratio [OR] 1.88, 95% confidence interval [CI] 1.01 to 2.75, p <0.05), nondialysis diabetics (OR 4.27, 95% CI 2.87 to 5.67, p <0.008), and nondialysis nondiabetics (OR 5.2, 95% CI 4.17 to 6.23, p <0.0001). [ABSTRACT FROM AUTHOR]

Antiplatelet therapy is a cornerstone in the medical management of acute coronary syndromes. Three classes of antiplatelet drugs are available in this setting: acetylsalicylic acid, thienopyridines, and glycoprotein IIb/IIIa antagonists. During the last ten years, numerous clinical trials have been conducted in large populations of patients suffering from acute coronary syndromes. Further investigations are in progress. In the light of these results, the respective roles of the different antiplatelet drugs have been more precisely defined, in terms of class preference as well as in terms of the combination of several antiplatelet drugs and of antiplatelet drugs with other therapies, including non fractionated — or low molecular weight — heparin and non-invasive or invasive revascularisation procedures. In the present article, we review the results of the major published or non published trials that addressed the role of glycoprotein IIb/IIIa antagonists in the management of acute coronary syndromes. Based on these results, the current therapeutic guidelines for clinical practice issued by the American and European cardiology societies are given in the conclusion, with their level of evidence. [Copyright &y& Elsevier]

To explore threats and opportunities and to chart a path for safely navigating the rapid changes that generative artificial intelligence (AI) will bring to clinical research, the Duke Clinical Research Institute convened a multidisciplinary think tank in January 2024. Leading experts from academia, industry, nonprofits, and government agencies highlighted the potential opportunities of generative AI in automation of documentation, strengthening of participant and community engagement, and improvement of trial accuracy and efficiency. Challenges include technical hurdles, ethical dilemmas, and regulatory uncertainties. Success is expected to require establishing rigorous data management and security protocols, fostering integrity and trust among stakeholders, and sharing information about the safety and effectiveness of AI applications. Meeting insights point towards a future where, through collaboration and transparency, generative AI will help to shorten the translational pipeline and increase the inclusivity and equitability of clinical research., Competing Interests: Funding support and author disclosures Funding support for the meeting from which this consensus document was generated was provided through registration fees from the following industry sponsors: Alnylam Pharmaceuticals, Inc (Cambridge, MA, USA); Amgen, Inc (Apex, NC, USA); AstraZeneca (Durham, NC, USA); Bayer Pharma AG (Berlin, Germany); Boehringer Ingelheim Pharma GmbH & Co KG (Ingelheim am Rhein, Germany); Bristol Myers Squibb Company (New York, NY, USA); Intellia Therapeutics, Inc (Cambridge, MA, USA); Janssen Pharmaceuticals (Beerse, Belgium); Companies of Johnson & Johnson (New Brunswick, NJ, USA); Novartis AG (Basel, Switzerland); and Novo Nordisk A/S (Bagsværd, Denmark). No government funds were used for this meeting. The think tank was funded by industry sponsors with representation at the meeting. Dr Foote is supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development under awards T32HD094671 and T32HD104576. Dr Borentain has stock or stock options with Bayer and is a Bayer employee. Dr Dreyer received travel support for attendance at a meeting by Picnic Health and has stock options from Picnic Health. Dr Fessel received payment for a lecture given at the University for Continuing Education, Kremes, Austria, and received travel support from Boehringer Ingelheim Pharma GmbH & Co KG, Department of Global Biostatistics & Data Sciences. Dr Goyal received travel support from Alnylam Pharmaceuticals for attendance at the think tank meeting and receives stock and stock options for Alnylam Pharmaceuticals as an employee. NG is also the co-founder of the patient recruitment platforms iTrials. Hanger works for the Clinical Trials Transformation Initiative, which is supported primarily by an award from the Food and Drug Administration (FDA) of the U.S. Department of Health and Human Services (HHS), with an additional 15% from nongovernmental entities (member organizations); also received travel support from the National Academies of Sciences, Engineering, Medicine Forum on Drug Discovery, Development, and Translation. Dr Hernandez has received grants or contracts from Pfizer Inc and Merck and consulting fees from Merck. Dr Lindsay has stock or stock options with GSK and Johnson & Johnson. Dr Hornik has received grants from the National Institutes of Health (award numbers: 5R01-HD106588-02, 1RL1-HD107784-03, 5R33-HL147833-05, 5T32HD104576-03, OT2OD034481, and 1U01-MD018294-01) and Burroughs Wellcome (1020016) and has received consulting fees from Lightship Inc, Cytokinetics, and UCB Pharma; and also has participated on an advisory board for The Emmes Corporation, LLC. Dr Matheny has received consulting fees from the Patient-Centered Outcomes Research Institute (PCORI) trust fund. Dr Ozer has stock with Novo Nordisk and is a Novo Nordisk employee. Dr Lindsell has received grants or contracts from the following, with all payments made to the institution: the National Institutes of Health, the Department of Defense, the U.S. Centers for Disease Control and Prevention, Novartis, AstraZeneca, Cytokinetics, Biomeme, Entegrion Inc, Endpoint Health, and bioMerieux; In addition, patents for risk stratification in sepsis and septic shock were issued to Cincinnati Children's Hospital Medical Center; has also participated in data safety monitoring boards unrelated to the current work and has participated on Clinical and Translational Science Awards (CTSA) external advisory boards; is also an ex officio member of Association for Clinical and Translational Science (ACTS) board, Clinical Research Forum (CRF) board, ACTS Advisory Committee, and the Center for Clinical and Translational Science (CCTS) Executive Committee; and has stock options with Bioscape Digital. In addition, CJL is the Editor-in-Chief of the Journal of Clinical and Translational Science. CH, JJ, KB, MA, NS, and PJE report no conflicts of interest. The first draft of the manuscript was written independently of sponsor input. Industry representatives were able to provide comments on subsequent drafts of the manuscript. The ultimate decision to include these comments rested with the primary and senior authors., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Patients with heart failure (HF) and a recent worsening heart failure (WHF) event are known to be at high risk of recurrent hospitalization and death, regardless of ejection fraction., Objectives: This study examined the efficacy and safety of the nonsteroidal mineralocorticoid receptor antagonist (MRA) finerenone in relation to the recency of a WHF event., Methods: FINEARTS-HF (FINerenone trial to investigate Efficacy and sAfety superioR to placebo in paTientS with Heart Failure) was a randomized, double-blind, placebo-controlled trial of finerenone in patients with HF and left ventricular ejection fraction ≥40%. In this prespecified analysis, we assessed the risk of cardiovascular (CV) events and response to finerenone vs placebo in relation to the time from WHF to randomization (during or within 7 days, 7 days to 3 months, >3 months, or no prior WHF). The primary outcome was a composite of total (first and recurrent) WHF events and CV death, analyzed using a proportional rates method., Results: Of 6,001 patients validly randomized to finerenone or placebo, 1,219 (20.3%) were enrolled during (749 [12.5%]) or within 7 days (470 [7.8%]), 2,028 (33.8%) between 7 days and 3 months, and 937 (15.6%) >3 months from a WHF event; 1,817 (30.3%) had no prior history of WHF. Rates of the primary composite outcome varied inversely with time since WHF, with >2-fold higher risk in those enrolled during or within 7 days of WHF compared with those enrolled >3 months from WHF or without prior WHF (risk ratio [RR]: 2.13; 95% CI: 1.82-2.55). Compared to placebo, finerenone appeared to lower the risk of the primary composite to a greater extent in those enrolled within 7 days of WHF (RR: 0.74; 95% CI: 0.57-0.95) or between 7 days and 3 months of WHF (RR: 0.79; 95% CI: 0.64-0.97) than in those >3 months from WHF or without prior WHF (RR: 0.99; 95% CI: 0.81-1.21); however, no definitive treatment-by-time interaction could be confirmed (P = 0.07). Greater absolute risk reductions with finerenone were accordingly seen in those with recent WHF (P trend  = 0.011). The risk of adverse events including hyperkalemia and worsening renal function among patients assigned to finerenone was not increased in those with recent WHF., Conclusions: Compared with those without recent WHF, patients with HF and mildly reduced or preserved ejection fraction who have experienced a recent WHF event are at higher risk for recurrent HF events and CV death; a possible signal of enhanced absolute treatment benefit with finerenone in this population requires further confirmation in future studies. (Study to Evaluate the Efficacy [Effect on Disease] and Safety of Finerenone on Morbidity [Events Indicating Disease Worsening] & Mortality [Death Rate] in Participants With Heart Failure and Left Ventricular Ejection Fraction [Proportion of Blood Expelled Per Heart Stroke] Greater or Equal to 40% [FINEARTS-HF], NCT04435626; A study to gather information on the influence of study drug finerenone on the number of deaths and hospitalizations in participants with heart failure EudraCT 2020-000306-29)., Competing Interests: Funding Support and Author Disclosures The FINEARTS-HF trial was funded by Bayer AG. Dr Desai has received institutional research grants (to Brigham and Women’s Hospital) from Abbott, Alnylam, AstraZeneca, Bayer, Novartis, and Pfizer; and has received personal consulting fees from Abbott, Alnylam, AstraZeneca, Bayer, Biofourmis, Boston Scientific, Medpace, Medtronic, Merck, Novartis, Parexel, Porter Health, Regeneron, River2Renal, Roche, Veristat, Verily, and Zydus. Dr Vaduganathan has received research grant support, served on advisory boards, or had speaker engagements with American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Bristol Myers Squibb, Boehringer Ingelheim, Chiesi, Cytokinetics, Fresenius Medical Care, Idorsia Pharmaceuticals, Lexicon Pharmaceuticals, Merck, Milestone Pharmaceuticals, Novartis, Novo Nordisk, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health; and participates on clinical trial committees for studies sponsored by AstraZeneca, Galmed, Novartis, Bayer AG, Occlutech, and Impulse Dynamics. Dr Claggett has received personal consulting fees from Alnylam, Bristol Myers Squibb, Cardior, Cardurion, Corvia, CVRx, Eli Lilly, Intellia, and Rocket; and has served on a data safety monitoring board for Novo Nordisk. Dr Jhund has received speaker fees from AstraZeneca, Novartis, Alkem Metabolics, ProAdWise Communications, and Sun Pharmaceuticals; has received advisory board fees from AstraZeneca, Boehringer Ingelheim, and Novartis; has received research funding from AstraZeneca, Boehringer Ingelheim, Analog Devices Inc, and Roche Diagnostics; his employer, the University of Glasgow, has been remunerated for clinical trial work from AstraZeneca, Bayer AG, Novartis, and Novo Nordisk; and he is Director of GCTP Ltd. Dr Cunningham has received personal consulting fees from Roche Diagnostics, Occlutech, KCK, and Edgewise Therapeutics. Mr Lay-Flurrie is a full-time employee of Bayer PLC, Research and Development, Pharmaceuticals. Drs Borentain, Viswanathan, Rohwedder, and Amarante are employees of Bayer AG. Dr Lam has received research support from Novo Nordisk and Roche Diagnostics; has received consulting fees from Alleviant Medical, Allysta Pharma, AnaCardio AB, Applied Therapeutics, AstraZeneca, Bayer, Biopeutics, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, CardioRenal, CPC Clinical Research, Eli Lilly, Impulse Dynamics, Intellia Therapeutics, Ionis Pharmaceutical, Janssen Research and Development LLC, Medscape/WebMD Global LLC, Merck, Novartis, Novo Nordisk, Prosciento Inc, Quidel Corporation, Radcliffe Group Ltd, Recardio Inc, ReCor Medical, Roche Diagnostics, Sanofi, Siemens Healthcare Diagnostics, and Us2.ai; and is a cofounder and nonexecutive director of Us2.ai. Dr Senni has served on advisory boards for and received consultancy and honoraria from Novartis, Abbott, Merck, MSD, Vifor, AstraZeneca, Cardurion, Novo Nordisk, Bayer, and Boehringer Ingelheim. Dr Shah has received research grants from National Institutes of Health (U54 HL160273, X01 HL169712, R01 HL140731, R01 HL149423), American Heart Association (24SFRNPCN1291224), AstraZeneca, Corvia, and Pfizer; and has received consulting fees from Abbott, Alleviant, AstraZeneca, Amgen, Aria CV, Axon Therapies, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cyclerion, Cytokinetics, Edwards Lifesciences, Eidos, Imara, Impulse Dynamics, Intellia, Ionis, Lilly, Merck, MyoKardia, Novartis, Novo Nordisk, Pfizer, Prothena, Regeneron, Rivus, Sardocor, Shifamed, Tenax, Tenaya, and Ultromics. Dr Voors’ employer has received consultancy fees and/or research support from Adrenomed, Anacardio, AstraZeneca, Bayer AG, Bristol Myers Squibb, Boehringer Ingelheim, Corteria, Eli Lilly, Merck, Moderna, Novartis, Novo Nordisk, Roche Diagnostics, and SalubrisBio. Dr Zannad has received personal fees from 89Bio, Abbott, Acceleron, Applied Therapeutics, Bayer, Betagenon, Boehringer, Bristol Myers Squibb, CVRx, Cambrian, Cardior, Cereno Pharmaceutical, Cellprothera, CEVA, Inventiva, KBP, Merck, Novo Nordisk, Owkin, Otsuka, Roche Diagnostics, Northsea, and USa2; has stock options at G3Pharmaceutical and equities at Cereno, Cardiorenal, and Eshmoun Clinical research; and is the founder of Cardiovascular Clinical Trialists. Dr Pitt is a consultant for Bayer, AstraZeneca, Boehringer Ingelheim, Lexicon, Bristol Myers Squibb, KBP Biosciences, Sarfez Pharmaceuticals, SQinnovations, G3 Pharmaceuticals, Sea Star Medical, Vifor Prointel, and Brainstorm Medical; has stock/stock options in KBP Biosciences, Sarfez Pharmaceuticals, SQinnovations, G3 Pharmaceuticals, Sea Star Medical, Vifor Prointel, and Brainstorm Medical; and holds U.S. Patent 9931412, site specific delivery of eplerenone to the myocardium, and U.S. Patent pending 63/045,783 Histone modulating agents for the prevention and treatment of organ failure. Dr Kosiborod has received grants, personal fees, and other from AstraZeneca and Vifor Pharma; has received grants and personal fees from Boehringer Ingelheim and Pfizer; has received personal fees from 35Pharma, Alnylam, Amgen, Applied Therapeutics, Arrowhead Pharmaceuticals, Bayer, Cytokinetics, Dexcom, Eli Lilly, Esperion Therapeutics, Imbria Pharmaceuticals, Janssen, Lexicon Pharmaceuticals, Merck (Diabetes and Cardiovascular), Novo Nordisk, Pharmacosmos, Regeneron, Sanofi, scPharmaceuticals, Structure Therapeutics, and Youngene Therapeutics; and other from Artera Health, Saghmos Therapeutics, outside of the submitted work. Dr McMurray has received payments through Glasgow University for work on clinical trials; has consulted for and received grants from Amgen, AstraZeneca, Bayer, Cardurion, Cytokinetics, GlaxoSmithKline, and Novartis; and has received personal consultancy fees from Alnylam Pharmaceuticals, Amgen, AnaCardio, AstraZeneca, Bayer, Berlin Cures, Bristol Myers Squibb, Cardurion, Cytokinetics, Ionis Pharmaceuticals, Novartis, Regeneron Pharmaceuticals, River 2 Renal Corp, British Heart Foundation, National Institute for Health, National Heart, Lung, and Blood Institute, Boehringer Ingelheim, SQ Innovations, and the Catalyze Group; has received personal lecture fees from Abbott, Alkem Metabolics, AstraZeneca, Blue Ocean Scientific Solutions Ltd, Boehringer Ingelheim, Canadian Medical and Surgical Knowledge, Emcure Pharmaceuticals Ltd, Eris Lifesciences, European Academy of CME, Hikma Pharmaceuticals, Imagica Health, Intas Pharmaceuticals, J.B. Chemicals and Pharmaceuticals Ltd, Lupin Pharmaceuticals, Medscape/Heart.Org., ProAdWise Communications, Radcliffe Cardiology, Sun Pharmaceuticals, The Corpus, Translation Research Group, and Translational Medicine Academy; has served on the Data Safety Monitoring Board of WIRB-Copernicus Group Clinical Inc; and is a director of Global Clinical Trial Partners Ltd. Dr Solomon has received research grants from Alexion, Alnylam, AstraZeneca, Bellerophon, Bayer, Bristol Myers Squibb, Boston Scientific, Cytokinetics, Edgewise, Eidos, Gossamer, GlaxoSmithKline, Ionis, Lilly, MyoKardia, National Institutes of Health, National Heart, Lung, and Blood Institute, Novartis, Novo Nordisk, Respicardia, Sanofi Pasteur, Theracos, and US2.AI; and has consulted for Abbott, Action, Akros, Alexion, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, GlaxoSmithKline, Lilly, Merck, Myokardia, Novartis, Roche, Theracos, Quantum Genomics, Janssen, Cardiac Dimensions, Tenaya, Sanofi-Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, Sarepta, Lexicon, Anacardio, Akros, and Valo. Dr Kulac has reported that he has no relationships relevant to the contents of this paper to disclose., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: To investigate the effects of Cimlanod, a nitroxyl donor with vasodilator properties, on water and salt excretion after an administration of an intravenos bolus of furosemide., Methods and Results: In this randomized, double-blind, mechanistic, crossover trial, 21 patients with left ventricular ejection fraction <45%, increased plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and receiving loop diuretics were given, on separate study days, either an 8 h intravenous (IV) infusion of cimlanod (12 μg/kg/min) or placebo. Furosemide was given as a 40 mg IV bolus four hours after the start of infusion. The primary endpoint was urine volume in the 4 h after the bolus of furosemide during infusion of cimlanod compared with placebo. Median NT-proBNP at baseline was 1487 (interquartile range: 847-2665) ng/L. Infusion of cimlanod increased cardiac output and reduced blood pressure without affecting cardiac power index consistent with its vasodilator effects. Urine volume in the 4 h post-furosemide was lower with cimlanod (1032 ± 393 ml) versus placebo (1481 ± 560 ml) (p = 0.002), as were total sodium excretion (p = 0.004), fractional sodium excretion (p = 0.016), systolic blood pressure (p < 0.001), estimated glomerular filtration rate (p = 0.012), and haemoglobin (p = 0.010), an index of plasma volume expansion., Conclusions: For patients with heart failure and congestion, vasodilatation with agents such as cimlanod reduces the response to diuretic agents, which may offset any benefit from acute reductions in cardiac preload and afterload., (© 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: Nitroxyl provokes vasodilatation and inotropic and lusitropic effects in animals via post-translational modification of thiols. We aimed to compare effects of the nitroxyl donor cimlanod (BMS-986231) with those of nitroglycerin (NTG) or placebo on cardiac function in patients with chronic heart failure with reduced ejection fraction (HFrEF)., Methods and Results: In a randomized, multicentre, double-blind, crossover trial, 45 patients with stable HFrEF were given a 5 h intravenous infusion of cimlanod, NTG, or placebo on separate days. Echocardiograms were done at the start and end of each infusion period and read in a core laboratory. The primary endpoint was stroke volume index derived from the left ventricular outflow tract at the end of each infusion period. Stroke volume index with placebo was 30 ± 7 mL/m 2 and was lower with cimlanod (29 ± 9 mL/m 2 ; P = 0.03) and NTG (28 ± 8 mL/m 2 ; P = 0.02). Transmitral E-wave Doppler velocity on cimlanod or NTG was lower than on placebo and, consequently, E/e' (P = 0.006) and E/A ratio (P = 0.003) were also lower. NTG had similar effects to cimlanod on these measurements. Blood pressure reduction was similar with cimlanod and NTG and greater than with placebo., Conclusion: In patients with chronic HFrEF, the haemodynamic effects of cimlanod and NTG are similar. The effects of cimlanod may be explained by venodilatation and preload reduction without additional inotropic or lusitropic effects. Ongoing trials of cimlanod will further define its potential role in the treatment of heart failure., (© 2021 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Introduction: This study described patients hospitalized for acute heart failure (AHF) in Japan who received intravenous (IV) diuretics and/or vasodilators as the initial therapy., Methods: The Japan Medical Data Vision database was used to identify adult patients hospitalized for AHF during 2013-2017, who were hemodynamically stable at presentation and treated with IV diuretics and/or IV vasodilators as initial therapy. Treatment patterns and use of cardiac rehabilitation, as well as outcomes (e.g., length of stay [LOS], in-hospital mortality, HF-readmission) were reported overall and by year of AHF hospitalization., Results: Of 30,360 patients (mean age = 80.0 years; 52.2% male), 87.0% were treated during the hospitalization with IV diuretics, 63.9% with IV vasodilators, and 13.8% with intensified therapies. On average, the duration of IV therapy was 10.6 days. In-hospital cardiac rehabilitation was utilized by 51.7% of the patients for 11.7 days on average. Mean LOS was 23.3 days, while in-hospital mortality and 30-day HF readmission post-discharge were 13.2 and 9.5%, respectively. Hospitalization outcomes remained stable between 2013 and 2017 despite important changes in AHF management such as a decrease in carperitide use (55.9-40.0% in 2017), and increases in use of tolvaptan (from 14.2% in 2013 to 31.3% in 2017) and of cardiac rehabilitation (from 43.2% in 2013 to 56.1% in 2017). Patients with intensified therapies had the longest IV therapy duration (mean 23.8 days vs. 5.5-9.9 days), the highest cardiac rehabilitation services use (60.2 vs. 38.3-57.0%), the longest LOS (mean 36.7 vs. 16.3-22.2 days), and the highest in-hospital mortality (37.4 vs. 3.1-12.4%) compared to the other treatment groups., Conclusions: Contemporary treatment for AHF hospitalization in Japan comprises a long duration of IV therapy followed by extended use of oral medications and in-hospital cardiac rehabilitation prior to discharge. Patients requiring intensified therapies had much longer LOS and higher in-hospital mortality.

Objectives: The primary objective was to identify well-tolerated doses of cimlanod in patients with acute heart failure (AHF). Secondary objectives were to identify signals of efficacy, including biomarkers, symptoms, and clinical events., Background: Nitroxyl (HNO) donors have vasodilator, inotropic and lusitropic effects. Bristol-Myers Squibb-986231 (cimlanod) is an HNO donor being developed for acute heart failure (AHF)., Methods: This was a phase IIb, double-blind, randomized, placebo-controlled trial of 48-h treatment with cimlanod compared with placebo in patients with left ventricular ejection fraction ≤40% hospitalized for AHF. In part I, patients were randomized in a 1:1 ratio to escalating doses of cimlanod or matching placebo. In part II, patients were randomized in a 1:1:1 ratio to either of the 2 highest tolerated doses of cimlanod from part I or placebo. The primary endpoint was the rate of clinically relevant hypotension (systolic blood pressure <90 mm Hg or patients became symptomatic)., Results: In part I (n = 100), clinically relevant hypotension was more common with cimlanod than placebo (20% vs. 8%; relative risk [RR]: 2.45; 95% confidence interval [CI]: 0.83 to 14.53). In part II (n = 222), the incidence of clinically relevant hypotension was 18% for placebo, 21% for cimlanod 6 μg/kg/min (RR: 1.15; 95% CI: 0.58 to 2.43), and 35% for cimlanod 12 μg/kg/min (RR: 1.9; 95% CI: 1.04 to 3.59). N-terminal pro-B-type natriuretic peptide and bilirubin decreased during infusion of cimlanod treatment compared with placebo, but these differences did not persist after treatment discontinuation., Conclusions: Cimlanod at a dose of 6 μg/kg/min was reasonably well-tolerated compared with placebo. Cimlanod reduced markers of congestion, but this did not persist beyond the treatment period. (Evaluate the Safety and Efficacy of 48-Hour Infusions of HNO (Nitroxyl) Donor in Hospitalized Patients With Heart Failure [STANDUP AHF]; NCT03016325)., Competing Interests: Funding Support and Author Disclosures The STAND-UP AHF study was funded by Bristol Myers Squibb. Dr. Felker has received research grants from National Heart, Lung, and Blood Institute, American Heart Association, Amgen, Bayer Merck, Cytokinetics, Myokardia, Bayer, and Roche Diagnostics; and he has been a consultant for Novartis, Amgen, Bristol-Myers Squibb, Cytokinetics, Medtronic, Cardionomic, V-Wave, Myokardia, Innolife, EBR Systems, Arena, Abbott, Roche Diagnostics, Alnylam, LivaNova, Eidos Therapeutics, Rocket Pharma, Reprieve, and SC Pharma. Dr. McMurray has been a consultant for Alnylam, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Cardurion, Cytokinetics, DalCor, GlaxoSmithKline, Merck, Novartis, Pfizer, Servier Theracos, and Vifor-Fresenius. Dr. Cleland has received personal grants and personal fees from Bristol Myers Squibb for the submitted work; has received personal fees from Abbott; has received grants and personal fees from Amgen, Bayer, Novartis, Myokardia, Pharmacosmos, Vifor, Bristol-Myers Squibb, and Servier, outside of the submitted work; and had received personal fees and non-financial support from Medtronic. Dr. O’Connor has been a consultant for Bristol Myers Squibb Foundation, Bayer, and Merck. Dr. Teerlink has received research grants and/or consulting fees from Abbott, Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Cytokinetics, EBR Systems, Medtronic, Merck, and Novartis. Dr. Voors has received research support and/or has been a consultant for Amgen, AstraZeneca, Bayer AG, Boehringer Ingelheim, Cytokinetcs, Merck, Myokardia, NovoNordisk, Novartis, and Roche Diagnostics. Dr. Belohlavek has received funding from Bristol-Myers Squibb for the conduct of this study. Dr. Bueno has received research funding from the Instituto de Salud Carlos III, Spain (PIE16/00021 & PI17/01799), Sociedad Española de Cardiología, AstraZeneca, Bayer, Bristol-Myers Squibb, and Novartis; has received consulting fees from AstraZeneca, Bayer, Bristol-Myers Squibb-Pfizer, Novartis; and has received speaker fees or support for attending scientific meetings from Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb-Pfizer, Novartis, and MEDSCAPE-the heart.og. Drs. Borentain, DeSouza, Kessler, Seiffert, and Ye are employees of Bristol Myers Squibb. Dr. Böhm has been supported by the Deutsche Forschungsgemeinschaft (SFB TTR 219, S-01); and has received consultant and speaking honoraria from Abbott, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol Myers Squibb, Medtronic, Novartis, ReCor, Servier, and Vifor. Dr. Ezekowitz has received research grants or honoraria from CIHR, Canadian Cardiovascular Society, Amgen, Bayer, Merck, and Cytokinetics. Dr. Filippatos has been a committee member in trials sponsored by Medtronic, Novartis, Vifor, Boehringer Ingelheim, Bristol-Myers Squibb, Servier, and Bayer. Dr. Lang has received research, grant or other support from AstraZeneca, Bristol-Myers Squibb, Novartis, Takeda, Vifor Pharma, Pfizer, and Roche. Dr. Martinez has received research grants and/or honoraria from Novartis, AstraZeneca, Bayer, Pfizer, Bristol-Myers Squibb, Gador, Baliarda, and Boehringer Ingelheim. Dr Mebazaa has received speaker's honoraria from Orion, Otsuka, Philips, Roche, and Servier; and has received fees as a member of advisory board and/or the steering committee and/or has received research grants from 4TEEN4, Abbott, Adrenomed, Bristol Myers Squibb, Epygon, Fire1, Roche, Sanofi, and Sphyngotec. Dr. Metra has received consulting honoraria from Amgen, LivaNova, and Vifor Pharma as trials’ committees member, from Abbott Vascular and Bayer as a participant to an advisory board, and from Abbott Vascular and Edwards Therapeutics as speaker at an industry sponsored meeting. Dr. Mosterd has received a research grant from Novartis; has been a consultant to Amarin, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, MSD, and Pfizer. Dr. Pang has been a consultant for Baxter, Bristol-Myers Squibb, and Merck; and has received research, grants, or other support from Bristol-Myers Squibb, Roche, Novartis, PCORI, AHA, National Heart, Lung, and Blood Institute, AHRQ, OrthoDiagnostics, and Abbott. Dr. Ponikowski has received consulting fees and speaker’s honoraria from Vifor Pharma, Amgen, Servier, Novartis, Berlin Chemie, Bayer, Pfizer, Cibiem, Impulse Dynamics, Renal Guard Solutions, Boehringer Ingelheim, and AstraZeneca; and has received research grants from Vifor Pharma. Dr. Sato has received personal fees from Bristol-Myers Squibb, during the conduct of the study; has received honoraria and consultant fees from Otsuka, Ono, Terumo, Bayer, Novartis, Roche Diagnostics Japan, and Daiichi-Sankyo, outside the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to characterize in-hospital treatment patterns and associated patient outcomes among patients hospitalized for heart failure (HF) in U.S. clinical practice., Background: Hospitalizations for HF are common and associated with poor patient outcomes. Real-world patterns of in-hospital treatment, including diuretic therapy, in contemporary U.S. practice are unknown., Methods: Using Optum de-identified Electronic Health Record data from 2007 through 2018, patients hospitalized for a primary diagnosis of HF (ejection fraction ≤40%) and who were hemodynamically stable at admission, without concurrent acute coronary syndrome or end-stage renal disease, and treated with intravenous (IV) diuretic agents within 48 h of admission were identified. Patients were categorized into 1 of 4 mutually exclusive hierarchical treatment groups defined by complexity of treatment during hospitalization (intensified treatment with mechanical support or IV vasoactive therapy, IV diuretic therapy reinitiated after discontinuation for ≥1 day without intensified treatment, IV diuretic dose increase/combination diuretic treatment without intensified treatment or IV diuretic reinitiation, or uncomplicated)., Results: Of 22,677 patients hospitalized for HF with reduced ejection fraction (HFrEF), 66% had uncomplicated hospitalizations without escalation of treatment beyond initial IV diuretic therapy. Among 7,809 remaining patients, the highest level of therapy received was IV diuretic dose increase/combination diuretic treatment in 25%, IV diuretic reinitiation in 36%, and intensified therapy in 39%. Overall, 19% of all patients had reinitiation of IV diuretic agents (26% of such patients had multiple instances), 12% were simultaneously treated with multiple diuretics, and 61% were transitioned to oral diuretic agents before discharge. Compared with uncomplicated treatment, IV diuretic reinitiation and intensified treatment were associated with significantly longer median length of stay (uncomplicated: 4 days; IV diuretic reinitiation: 8 days; intensified: 10 days) and higher rates of in-hospital (uncomplicated: 1.6%; IV diuretic reinitiation: 4.2%; intensified: 13.2%) and 30-day post-discharge mortality (uncomplicated: 5.2%; IV diuretic reinitiation: 9.7%; intensified: 12.7%)., Conclusions: In this contemporary real-world population of U.S. patients hospitalized for HFrEF, one-third of patients had in-hospital treatment escalated beyond initial IV diuretic therapy. These more complex treatment patterns were associated with highly variable patterns of diuretic use, longer hospital lengths of stay, and higher mortality. Standardized and evidence-based approaches are needed to improve the efficiency and effectiveness of in-hospital HFrEF care., Competing Interests: Author Relationship With Industry Dr. Greene has received a Heart Failure Society of America/Emergency Medicine Foundation Acute Heart Failure Young Investigator Award funded by Novartis; has received research support from Amgen, AstraZeneca, Bristol-Myers Squibb, Merck, and Novartis; serves on Advisory Boards for Amgen and Cytokinetics; and serves as a consultant for Amgen and Merck. Drs. Ionescu-Ittu and Burne and Ms. Guérin are employees of Analysis Group Inc., which has received consultancy fees from Bristol-Myers Squibb for this study. Drs. Borentain, Kessler, Tugcu, and DeSouza are employees of Bristol-Myers Squibb. Dr. Felker has received research funding from Otsuka, Novartis, Roche Diagnostics, Amgen, Merck, the American Heart Association, and the National Heart, Lung, and Blood Institute; and has served as a consultant for Novartis, Roche Diagnostics, Amgen, Trevena, Cytokinetics, Madeleine, MyoKardia, Bristol-Myers Squibb, Stealth Biotherapeutics, and GlaxoSmithKline. Dr. Chen was an employee of Bristol-Myers Squibb at the time the research was conducted. Dr. Triana has reported that she has no relationships relevant to the contents of this paper to disclose., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Hospitalisation for acute heart failure remains a major public health problem with high prevalence, morbidity, mortality, and cost. Prior attempts to develop new therapies for this condition have not been successful. Nitroxyl (HNO) plays a unique role in cardiovascular physiology by direct post-translational modification of thiol residues on target proteins, specifically SERCA2a, phospholamban, the ryanodine receptor and myofilament proteins in cardiomyocytes. In animal models, these biological effects lead to vasodilatation, increased inotropy and lusitropy, but without tachyphylaxis, pro-arrhythmia or evidence of increased myocardial oxygen demand. BMS-986231 is an HNO donor being developed as a therapy for heart failure, and initial studies in patients with heart failure support the potential clinical value of these physiological effects. In this manuscript, we describe the ongoing phase II development programme for BMS-986231, which consists of three related randomised placebo-controlled clinical trials, StandUP-AHF, StandUP-Imaging and StandUP-Kidney, which are designed to provide evidence of tolerability and efficacy as well as confirm the anticipated physiological effects in patients with heart failure with reduced ejection fraction. These studies will set the stage for the further study of BMS-986231 in future phase III clinical trials., (© 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology.)

Despite the availability of a number of different classes of therapeutic agents with proven efficacy in heart failure, the clinical course of heart failure patients is characterized by a reduction in life expectancy, a progressive decline in health-related quality of life and functional status, as well as a high risk of hospitalization. New approaches are needed to address the unmet medical needs of this patient population. The European Medicines Agency (EMA) is undertaking a revision of its Guideline on Clinical Investigation of Medicinal Products for the Treatment of Chronic Heart Failure. The draft version of the Guideline was released for public consultation in January 2016. The Cardiovascular Round Table of the European Society of Cardiology (ESC), in partnership with the Heart Failure Association of the ESC, convened a dedicated two-day workshop to discuss three main topic areas of major interest in the field and addressed in this draft EMA guideline: (i) assessment of efficacy (i.e. endpoint selection and statistical analysis); (ii) clinical trial design (i.e. issues pertaining to patient population, optimal medical therapy, run-in period); and (iii) research approaches for testing novel therapeutic principles (i.e. cell therapy). This paper summarizes the key outputs from the workshop, reviews areas of expert consensus, and identifies gaps that require further research or discussion. Collaboration between regulators, industry, clinical trialists, cardiologists, health technology assessment bodies, payers, and patient organizations is critical to address the ongoing challenge of heart failure and to ensure the development and market access of new therapeutics in a scientifically robust, practical and safe way., (© 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.)

Aims: Cardiovascular disease is the most common cause of mortality and morbidity in the world, but the pharmaceutical industry's willingness to invest in this field has declined because of the many challenges involved with bringing new cardiovascular drugs to market, including late-stage failures, escalating regulatory requirements, bureaucracy of the clinical trial business enterprise, and limited patient access after approval. This contrasts with the remaining burden of cardiovascular disease in Europe and in the world. Thus, clinical cardiovascular research needs to adapt to address the impact of these challenges in order to ensure development of new cardiovascular medicines., Methods and Results: The present paper is the outcome of a two-day workshop held by the Cardiovascular Round Table of the European Society of Cardiology. We propose strategies to improve development of effective new cardiovascular therapies. These can include (i) the use of biomarkers to describe patients who will benefit from new therapies more precisely, achieving better human target validation; (ii) targeted, mechanism-based approaches to drug development for defined populations; (iii) the use of information technology to simplify data collection and follow-up in clinical trials; (iv) streamlining adverse event collection and reducing monitoring; (v) extended patent protection or limited rapid approval of new agents to motivate investment in early phase development; and (vi) collecting data needed for health technology assessment continuously throughout the drug development process (before and after approval) to minimize delays in patient access. Collaboration across industry, academia, regulators, and payers will be necessary to enact change and to unlock the existing potential for cardiovascular clinical drug development., Conclusions: A coordinated effort involving academia, regulators, industry, and payors will help to foster better and more effective conduct of clinical cardiovascular trials, supporting earlier availability of innovative therapies and better management of cardiovascular diseases., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Background: Despite its limitations, unfractionated heparin (UFH) is the recommended anticoagulant during percutaneous coronary intervention (PCI). Few randomized trials have compared low-molecular-weight heparin (LMWH) and UFH, and most lacked the power to detect a difference between the 2 anticoagulants in terms of safety or efficacy. Our objective was to perform a meta-analysis of randomized trials comparing the efficacy and safety of LMWH vs UFH as anticoagulants in the setting of PCI., Methods: We used MEDLINE, randomized trials presented at major cardiology conferences, and journal article bibliographies from January 1998 and September 2006. Two reviewers independently identified randomized studies comparing the intravenous administration of LMWH vs UFH among patients undergoing PCI. Data on sample size, baseline characteristics, and outcomes of interest were independently extracted and analyzed., Results: Thirteen trials including 7318 patients met the inclusion criteria. A total of 4201 patients (57.4%) received LMWH, and 3117 patients (42.6%) received UFH. Intravenous LMWH use was associated with a significant reduction in the risk of major bleeding compared with UFH (odds ratio [OR], 0.57; 95% confidence interval [CI], 0.40-0.82; P = .002). A trend toward a reduction in minor bleeding was also observed among LMWH-treated patients (OR, 0.75; 95% CI, 0.47-1.20; P = .24). Similar efficacy was observed between LMWH and UFH regarding the double end point of death or myocardial infarction (OR, 0.99; 95% CI, 0.79-1.24; P = .93). There were no significant differences in death, myocardial infarction, and urgent revascularization between patients receiving LMWH and those receiving UFH., Conclusion: The use of intravenous LMWH during PCI is associated with a significant reduction in major bleeding events compared with UFH, without compromising outcomes on hard ischemic end points.

In order to determine how renal transplantation modifies in hospital and long-term outcome after coronary angioplasty, we compared dialysis and renal transplant patients with control patients without renal failure. Seventy-five consecutive dialysis patients (group D) and 37 renal transplant patients (group T) undergoing coronary angioplasty, were compared with two control groups (groups control D and control T, respectively) matched 1:1 with groups D and T for clinical and angiographic characteristics. The mean follow-up was 50 months. The rate of angiographic success was high and comparable in the four groups (P=0.7). Renal transplant patients were younger than dialysis non-transplant patients (P=0.004). The risk of 4-year cardiac death and nonfatal myocardial infarction was higher in dialysis compared to control dialysis patients (OR 2.6, 95% CI 1.35--5.01, P=0.004), in transplant patients compared to control transplant patients (OR 9.93, 95% CI 1.17--84.04, P=0.03), and there was a trend toward a higher risk in dialysis than in renal transplant patients (OR 1.6, 95% CI 0.8--3.19, P=0.08). The risk of 4-year mortality was higher in dialysis patients than in the other three groups (31% in group D versus 19% in group T, 13% in group control D, and 0% in group control T, P<0.001). After adjusting for age, diabetes, and multivessel disease, long-term mortality risk was similar in dialysis and renal transplant patients. On multivariate analysis, renal function (P=0.002), age (P=0.005), and tobacco consumption (P=0.005) were independently associated with 4-year cardiac death. In patients with end-stage renal disease who undergo coronary angioplasty, renal transplantation was not independently associated with a lower long-term mortality compared to dialysis treatment. Both dialysis and renal transplant patients show lower survival rates compared to matched control patients., ((J Interven Cardiol 2005;18:331-337).)

Coronary arteries are the most frequent location of atherosclerosis. Coronary artery disease is the first cause of death related to atherothrombosis. In addition, patients with a prior history of acute coronary syndromes exhibit a 10% annual risk of recurrence. Although there seems to be a close correlation between the extension of CAD and the severity of atherosclerotic lesions in extra coronary arterial beds, the prevalence of these extracoronary asymptomatic lesions depends on their location. Hence, the prevalence of renal artery disease defined as stenosis > or = 50% or of peripheral artery disease defined as an ABI < 0.9 is estimated to be 20% up to 30%, whereas the prevalence of both carotid artery disease defined as stenosis > or = 70% or aortic aneurysm is estimated to be 5%. Conversely, the annual absolute risk of stroke among CAD patients is estimated at 1% while it remains unknown for vascular events related to PAD or aortic lesions. These data suggest that a systematic screening for asymptomatic extracoronary atherosclerotic lesions among CAD patients cannot be justified without a better knowledge of the prevalence of these lesions. In addition, the identification of the predicting factors for the presence and the development of these asymptomatic lesions is warranted. Finally, the potential benefit in terms of therapeutic intervention of such screening needs to be evaluated. These important issues warrant further clinical studies with appropriate design.

This meta-analysis assessed the rates of the efficacy and safety endpoints with intravenous low-molecular-weight heparin (LMWH) compared with unfractionated heparin (UFH) in patients undergoing percutaneous coronary intervention (PCI). Subcutaneous LMWH has compared favorably with UFH, but limited experience exists with intravenous LMWH for immediate anticoagulation in PCI. The meta-analysis included data from eight randomized trials in which patients received LMWH (n = 1,037) or UFH (n = 978) during PCI. Seven additional nonrandomized studies/registries were analyzed to assess the efficacy and safety of LMWH during PCI. Efficacy endpoints were ischemic events (usually a composite of death, myocardial infarction, and urgent revascularization) and the safety endpoint was bleeding (major, minor, or all bleeding). In the randomized studies, LMWH was comparable with UFH in terms of efficacy (6.2% vs. 7.5%) and major bleeding (0.9% vs. 1.8%). The analysis of pooled data, randomized or not, suggests potential improved efficacy (5.8% vs. 7.6%) and reduced major bleeding (0.6% vs. 1.8%) with LMWH (n = 3,787) compared with UFH (n = 978). During PCI, intravenous LMWH without coagulation monitoring has the potential to be at least as safe and efficacious as intravenous UFH. Further studies of LMWHs in PCI are therefore required., (Copyright 2005 Wiley-Liss, Inc)

Context: Glycoprotein IIb/IIIa (Gp IIb/IIIa) inhibitors improve myocardial reperfusion and clinical outcomes of patients undergoing primary percutaneous coronary intervention (PCI), but optimal timing of administration remains unclear. No systematic reviews have comprehensively examined the effects of early vs delayed administration of these agents., Objective: To perform a meta-analysis of randomized trials of early (prior to transfer to the catheterization laboratory) vs late (at the time of PCI) intravenous administration of Gp IIb/IIIa inhibitors in acute ST-segment elevation myocardial infarction (STEMI)., Data Sources: MEDLINE and the Cochrane Controlled Trials Register search of the literature over the past 10 years; papers presented at major cardiac conferences; consultation with national and international colleagues as well as Gp IIb/IIIa inhibitor drug manufacturers; and text and journal article bibliographies., Study Selection and Data Extraction: We examined trials of randomized comparisons between early administration at the point of initial contact (emergency department or ambulance) and late administration (catheterization laboratory) of Gp IIb/IIIa inhibitors in STEMI. Outcome data had to be available on both culprit artery patency evaluated by Thrombolysis in Myocardial Infarction (TIMI) flow grades on admission and mortality. Two authors independently reviewed abstracts or complete articles. Six studies met inclusion criteria. Independent data extraction was performed by 2 reviewers and confirmed by consensus., Data Synthesis: The 6 trials enrolled 931 STEMI patients treated with abciximab (3 trials) or tirofiban (3 trials) in combination with primary PCI. TIMI grade 2 or 3 flow (41.7% [194/465 vs 29.8% [139/466]) as well as TIMI grade 3 flow (20.3% [84/413] vs 12.2% [51/418]) were significantly more frequent in the early group compared with the late group (odds ratio [OR], 1.69; 95% confidence interval [CI], 1.28-2.22; P<.001; and OR, 1.85; 95% CI, 1.26-2.71; P<.001, respectively). The early administration of Gp IIb/IIIa inhibitors was associated with a 28% reduction of mortality from 4.7% to 3.4%, which was not significant but consistent with similar trends for reinfarction and the composite ischemic end point., Conclusions: In a meta-analysis of 6 randomized trials, early administration of Gp IIb/IIIa inhibitors in STEMI appeared to improve coronary patency with favorable trends for clinical outcomes. These findings are supportive of a strategy of facilitated PCI. Further evaluations in adequately powered large trials are awaited to confirm the clinical benefit of this strategy.

We report the case of a patient with a past history of coronary atherosclerosis treated with primary angioplasty 5 hours following an inferior myocardial infarction. Echocardiography performed during the procedure revealed a mediastinal tumour invading the tricuspid, responsible for the occlusion of the right coronary. Infarction due to tumour compression is a rare presentation of mediastinal tumour. Diagnosis relies on echocardiographic, CT or magnetic resonance imaging. The prognosis is linked to the tumour pathology.