Semaglutide in HFpEF and Obesity, Role of SGLT2 Inhibitors to Highlight ESC 2023

Drugs that started out as treatments for type 2 diabetes (T2D) but now have much bigger roles in chronic disease will be at the center of the upcoming European Society of Cardiology (ESC) 2023 Congress, which opens Friday in Amsterdam, the Netherlands.

It’s taken 3 years for the ESC Congress to reschedule its turn in Amsterdam, which was set to host this international gathering in 2020 when COVID-19 required an all-virtual format. This year’s Congress is also available online. The 2023 schedule is bursting with science: The Congress features 3751 abstracts, 30 late-breaking “hotline” trials across 9 sessions, and guidelines updates in acute coronary syndromes, cardiomyopathies, cardiovascular disease (CVD) and diabetes, and endocarditis; in addition, ESC will release an interim “focused update” of the 2021 heart failure (HF) guidelines.

STEP HFpEF. Interest in semaglutide, a once-weekly glucagon-like peptide-1 (GLP-1) receptor agonist, has only increased since the recent announcement of topline results for SELECT in obesity. The SELECT trial was a 17,000-patient study that evaluated the 2.4-mg dose of semaglutide vs placebo alongside standard of care to prevent major adverse cardiac events in patients with overweight or obesity and established CVD. The STEP HFpEF program features 2 randomized trials for patients with obesity and HF with preserved ejection fraction (HFpEF): one for those without T2D (529 patients) and the other, STEP HFpEF-DM (617 patients), which is for patients with T2D. The trials measured changes in patients' symptoms and quality of life as well as weight loss.

Kosiborod

McMurray

On Friday, cardiologist Mikhail Kosiborod, MD, will present the findings of STEP HFpEF. Kosiborod is vice president of research at Saint Luke’s Health System, director of cardiometabolic research, and co-director, Saint Luke’s Michael and Marlys Haverty Cardiometabolic Center of Excellence, Saint Luke’s Mid-America Heart Institute.

“This is a treatment targeting a common and increasing comorbidity in this type of heart failure,” John McMurray, MD, an HF expert from the University of Glasgow, Scotland, and ESC program chair, said in a statement. “Obesity is associated with much worse symptoms and functional capacity and a higher risk of hospitalization. We hope reducing obesity will help patients with HFpEF.”

In addition, Kosiborod will take part in a symposium Sunday discussing weight loss as a therapeutic target in HFpEF.

Results aplenty for SGLT2 inhibitors. Almost 8 years have passed since the landmark results from the EMPA-REG OUTCOME trial showed that a glucose-lowering drug could also reduce the risk of cardiovascular events. Since that time, the utility of the sodium glucose cotransporter-2 (SGLT2) inhibitor class—in treating a broad spectrum of HF, in reducing the risk of renal failure—has revolutionized cardiometabolic care. The drug class remains intensely competitive as drug sponsors continue to explore new benefits, while US consumers learn about empagliflozin (Jardiance, Boehringer Ingelheim and Eli Lilly) from TV ads.

Butler

ESC 2023 will feature both updated data from prior studies, including the EMPEROR trials that demonstrated empagliflozin’s HF benefits, and new results from EMPACT-MI, which examined empagliflozin’s ability to prevent HF hospitalization in patients who had already suffered a heart attack. Javed Butler, MD, MPH, MBA, of Baylor, Scott, and White Research Institute in Dallas, Texas, will present the results. On Monday, in a session on “Registries on Incident and Prevalent Heart Failure,” Butler will discuss RECORD-MI, which concerns HF complicating acute myocardial infarction.

Abstracts for dapagliflozin (Farxiga, AstraZeneca) will include subanalyses for the DELIVER and DAPA-HF studies in HF, including data for patients with deteriorated kidney function, as well as new cardiopulmonary data for patients with HFpEF and chronic obstructive pulmonary disease. In Monday’s registries session, Stefan James, MD, PhD, of Uppsala University in Sweden, will offer a presentation on the rationale and design of the DAPA-MI study involving patients without T2D and acute myocardial infarction.

Recent evidence favors starting SGLT2 inhibitors while patients are still in the hospital following an HF incident, but the real-world data study, EVOLUTION HF, will show this is easier said than done. Results will highlight the challenge of clinical inertia remains when it comes to initiating guideline-directed medical therapy.

Finally, the last hotline session of the meeting, which comes late Monday, will feature the presentation, “Prospective Meta-Analysis of SGTL2 Inhibitor Randomized Trials in COVID-19,” with Kosiborod and Muthiah Vaduganathan, MD, MPH, a cardiologist at Brigham And Women’s Hospital and an instructor at Harvard Medical School. A retrospective analysis published in JAMA Network Open in December, which evaluated records from more than 3 million patients, suggested that use of SGLT2 inhibitors in patients with T2D prior to COVID-19 infection was linked with fewer adverse outcomes.

Nicholls

More data from CLEAR Outcomes. Landmark results presented in March at the American College of Cardiology Scientific Sessions showed that the cholesterol therapy bempedoic acid (Nexletol, Esperion) cut the risk of major cardiovascular events by 13%. More results from this study are coming Saturday in Amsterdam. Stephen Nicholls, MBBS, PhD, of the Victorian Heart Institute, Monash University, Melbourne, Australia, will present the CLEAR Outcomes Total Events Analysis, and Kausik Ray, MD, FMedSci, will present CLEAR Outcomes by Glycemic Status.

Kirchhof

Results in anticoagulation. Friday’s hotline session will feature the NOAH-AFNET 6 trial, which ended early in September 2022. It evaluated the benefit of oral anticoagulation in patients with atrial high-rate episodes. Paulus Kirchhof, MD, of the University Heart & Vascular Center in Hamburg, Germany, will present the results. Said McMurray, “This trial attempts to answer the very important clinical question of whether we should use anticoagulant therapy in patients with brief episodes of atrial fibrillation (AF). We know that sustained AF leads to a high risk of stroke, which can be effectively and safely (with respect to bleeding) reduced by treatment with an anticoagulant—but is this also true for short episodes of AF?”

Studies that examine the impact of switching therapies to treat AF will gain importance, given predictions that a novel oral anticoagulant (NOAC) will be among the drugs affected by the Inflation Reduction Act. The law, passed a year ago, will allow Medicare to negotiate prices for 10 top drugs starting in 2026. A real-world study to be presented Friday will examine the impact of switching or continuing apixaban (Eliquis, Bristol Myers Squibb) or rivaroxaban (Xarelto, Janssen) among patients with nonvalvular AF.

Banerjee

Sliwa

Khan

Yancy

On Sunday, results from the FRAIL-AF study will be presented in a hotline session. This pragmatic, randomized, open-label study is designed to examine a group of patients underrepresented in original NOAC studies: the frail elderly. The study compared the safety of switching from vitamin K antagonists (VKA) for stroke prevention to a NOAC-based treatment strategy compared with continuing VKA-management.

Use of anticoagulation therapy for treatment of isolated distal deep vein thrombosis in patients with cancer will be explored in the ONCO DVT study, to be presented Monday at the final hotline session.

Hypertrophic cardiomyopathy. New results will be presented Monday for mavacamten (Camzyos, Bristol Myers Squibb), including a late-breaking oral presentation of the 56-week VALOR-HCM-LTE study, which is evaluating this therapy in patients with severe obstructive HCM who are eligible for septal reduction therapy.

Health equity. On Monday, the ESC Congress will feature a joint session with JAMA Cardiology, “Achieving Global Health Equity: A New Challenge in Heart Failure,” to be chaired by Robert Bonow, MD, of Northwestern University, Chicago, and Bettina Heidecker, MD, Charite University Hospital, Berlin. Speakers will be Shrilla Banerjee, MD, of Surrey and Sussex Healthcare Trust, Redhill, United Kingdom; Karen Sliwa, MD, PhD, of the University of Cape Town, South Africa; and Sadiya Khan, MD, and Clyde Yancy, MD, both of Northwestern University.