Evidence and Mechanisms of Pharmacologic Benefit
A paradigm shift in the pharmacologic treatment of the diabetic heart in patients with type 2 diabetes (T2D) is underway. T2D is associated with approximately a 70% increased risk in death from CV causes and double and quintuple the risk of heart failure (HF) in diabetic men and women in the Framingham heart study. Until recently, tight glucose control with aggressive management of HgbA1C levels has failed to convincingly demonstrate benefit in CV events. In fact, concerns about CV safety and exacerbation of heart failure with some compounds such as the glitazones led to the FDA’s 2008 requirement for post-marketing assessment of all new T2D pharmacotherapies.
The recent impressive CV benefits of the sodium-glucose cotransporter 2 (SGLT-2) inhibitor, empaglaflozin, in the EMPA-REG outcomes trial and subsequent reports of CV event reductions with glucagon-like peptide 1 (GLP-1) analogues have led to a dramatic turnaround in thinking about treatment of the diabetic heart. While the recent FDA approval of empaglaflozin was based on a 38% reduction in CV death in EMPA-REG, an unexpected and unprecedented 35% reduction of heart failure (HF) hospitalizations has generated widespread interest in the use of SGLT-2 inhibitors in patients with diabetic cardiomyopathy as well as non-diabetic heart failure populations. The reproducibility and mechanisms of this effect remain to be explored.
In this webinar we will first provide a high level review of the medical underpinnings of the diabetic heart particularly as it relates to heart failure. Understanding the structural, metabolic and functional associations of T2D will help us to better understand how some molecular classes could lead to benefits in CV outcomes while others may be detrimental.
In the second presentation we will review the recent literature in the treatment of the diabetic heart and consider where the underlying pathophysiology and clinical trial results could lead to future innovations in the pharmacotherapy of diabetic heart failure. We will address trial designs in diabetic heart failure and opportunities for innovation.
Presented by
Jonathan F. Plehn MD, FACC,
Vice President, Cardiovascular Medicine, Covance Inc.; Clinical Professor of Medicine, Drexel University School of Medicine
Diabetic Heart Failure: Epidemiology and Mechanisms
Dr. Jonathan Plehn is Vice President of Cardiovascular Medicine at Covance Inc., a large contract research organization and Clinical Professor of Medicine at the Drexel University School of Medicine. Before joining industry Dr. Plehn was director of heart failure programs at the National Heart, Lung and Blood Institute, National Naval Medical Center and the George Washington University Medical Center. His early work at the Framingham Heart Study involved epidemiologic assessment of diastolic heart failure and risk prediction. He has participated in the design, oversight and execution of trials ranging from pre-clinical studies to large cardiovascular outcomes trials. He has over 140 publications and sits on the editorial board of the Journal of Cardiac Failure.
Darren McGuire MD, MHSc,
Professor of Internal Medicine, University of Texas Southwestern Medical Center
Effects of Antidiabetic Agents on Cardiovascular Outcomes: A Focus on Heart Failure
Dr. Darren K. McGuire, MD, MHSc is Professor of Medicine at UT Southwestern Medical Center in Dallas, Texas in the Division of Cardiology, where he holds the Dallas Heart Ball Chair for Research on Heart Disease in Women and is a Distinguished Teaching Professor. Dr. McGuire is the Lead Physician of the Parkland Hospital and Health System Cardiology clinics.
Dr. McGuire’s expertise is in large scale clinical trial design and execution, and drug registration/regulation, with a focus in the area of diabetes and cardiovascular disease. He presently has leadership roles for numerous international cardiovascular clinical outcomes trials, including T2DM, obesity, and lipid trials. Dr. McGuire is a previous member of the FDA Cardiovascular and Renal Drugs Advisory Committee and remains an FDA ad hoc consultant. He is Deputy Editor of Circulation and Senior Editor of Diabetes and Vascular Disease Research. Dr. McGuire has authored/co-authored over 240 peer-reviewed manuscripts, reviews, editorials and book chapters.
