Semaglutide versus placebo in people with obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF DM randomised trials

Butler, Javed; Shah, Sanjiv J; Petrie, Mark C; Borlaug, Barry A; Abildstrøm, Steen Z; Davies, Melanie J; Hovingh, G Kees; Kitzman, Dalane W; Møller, Daniél Vega; Verma, Subodh; Einfeldt, Mette Nygaard; Lindegaard, Marie L; Rasmussen, Søren; Abhayaratna, Walter; Ahmed, Fozia Z; Ben-Gal, Tuvia; Chopra, Vijay; Ezekowitz, Justin A; Fu, Michael; Ito, Hiroshi; Lelonek, Małgorzata; Melenovský, Vojtěch; Merkely, Bela; Núñez, Julio; Perna, Eduardo; Schou, Morten; Senni, Michele; Sharma, Kavita; van der Meer, Peter; Von Lewinski, Dirk; Wolf, Dennis; Kosiborod, Mikhail N

doi:10.1016/s0140-6736(24)00469-0

Cited by 64 publications

(3 citation statements)

References 48 publications

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“…As we raise the roof to celebrate the recent success of drugs that finally work to reduce symptoms, exercise intolerance, and heart failure hospitalizations in HFpEF, 14,15 we should also remember that the roof of the LA may be the Achilles' heel of the LA, the weak point that is a harbinger of the proverbial LA house falling apart, leading to LA myopathy and dysfunction. Whether it exists on an account of LV dysfunction or as a primary pathology, LA dysfunction lends vulnerability to symptoms, congestion, and clinical events in HFpEF.…”

Section: See Article By Backhaus Et Almentioning

confidence: 99%

Left Atrial Myopathy in Heart Failure With Preserved Ejection: Don’t Raise the Roof!

Patel,

Shah

2024

Circ: Cardiovascular Imaging

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Section: See Article By Backhaus Et Almentioning

confidence: 99%

Left Atrial Myopathy in Heart Failure With Preserved Ejection: Don’t Raise the Roof!

Patel,

Shah

2024

Circ: Cardiovascular Imaging

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“…7 GLP-1RA lead to a twofold reduction in heart-failure symptoms in people with heart failure with preserved ejection fraction, for those with either T2DM and obesity, or obesity alone. 8 Clinical guidelines now recommend GLP-1RA as one of the two recommended second-line treatments for adults with T2DM. 9 For adults with obesity and obesity-related co-morbidities, GLP-1RA are the first-line pharmacotherapy treatment.…”

Section: Introductionmentioning

confidence: 99%

“…The available clinical trials demonstrate that the patients most likely to benefit from GLP-1RA are older adults with cardiovascular disease and either T2DM or obesity. [1][2][3]5,7,8 However, the high out-of-pocket cost of GLP-1RA for adults without insurance has led to their preferential use among individuals with higher socioeconomic status. 16 Hospitalized adults are one of the highest risk groups for subsequent cardiovascular events, because inpatients have a median age of 73 years, have a median of six underlying chronic medical conditions, and the reason for the hospitalization can directly (e.g., hospitalization for myocardial infarction) or indirectly (e.g., influenza, COVID-19) increase a person's risk of subsequent cardiovascular events.…”

Section: Introductionmentioning

confidence: 99%

Glucagon-Like Peptide 1 Receptor Agonist Use in Hospital: A Multicentre Observational Study

Ray,

Moggridge,

Weisman

et al. 2024

Preprint

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IntroductionGlucagon-like peptide 1 receptor agonists (GLP-1RA) are effective medications for type 2 diabetes mellitus (T2DM) and obesity, yet their uptake among patients most likely to benefit has been slow.MethodsWe conducted a cross-sectional analysis of medication exposure in adults hospitalized at 16 hospitals in Ontario, Canada between 2015 and 2022. We estimated the proportion with T2DM, obesity, and cardiovascular disease. We identified the frequency of GLP-1RA use, and conducted multivariable logistic regression to identify factors associated with their use.ResultsAcross 1,278,863 hospitalizations, 396,084 (31%) patients had T2DM and approximately 327,844 (26%) had obesity. GLP-1RA use (n=1,274) was low among those with T2DM (0.3%) and those with obesity (0.7%), despite high prevalence of cardiovascular disease (36%). In contrast, use of diabetes medications lacking cardiovascular benefits was high, with 60% (n=236,612) receiving insulin and 14% (n=54,885) receiving sulfonylureas. Apart from T2DM (OR=29.6, 95% CI 23.5, 37.2), characteristics associated with greater odds of receiving GLP-1RA were age 50-70 years (OR=1.71, 95% CI 1.38, 2.11) compared to age < 50 years, hemoglobin A1C > 9% (OR=1.83, 95% CI 1.36, 2.47) compared to < 6.5%, and highest income quintile (OR=1.73, 95% CI 1.45, 2.07) compared to lowest income quintile.ConclusionKnowledge translation interventions are needed to address the low adoption of GLP-1RA among hospitalized patients with T2DM and obesity, who are the most likely to benefit.

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Intravenous and oral administration of the synthetic RNA drug, TY1, reverses heart failure with preserved ejection fraction in mice

Miyamoto,

Jones,

Yamaguchi

et al. 2024

Basic Res Cardiol

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TY1, a synthetic non-coding RNA (ncRNA) bioinspired by small Y RNAs abundant in extracellular vesicles (EVs), decreases cGAS/STING activation in myocardial infarction and thereby attenuates inflammation. Motivated by the concept that heart failure with preserved ejection fraction (HFpEF) is a systemic inflammatory disease, we tested TY1 in a murine model of HFpEF. Intravenous TY1, packaged in a transfection reagent, reversed the cardiac and systemic manifestations of HFpEF in two-hit obese-hypertensive mice, without inducing weight loss. The effects of TY1 were specific, insofar as they were not reproduced by a control RNA of the same nucleotide content but in scrambled order. TY1 consistently suppressed myocardial stress-induced MAP kinase signaling, as well as downstream inflammatory, fibrotic, and hypertrophic gene pathways in heart tissue. TY1 not only prevented but actually reversed key pathological processes underlying HFpEF, with no evidence of toxicity. Most noteworthy from a practical perspective, the effects of intravenous TY1 were reproduced by feeding HFpEF mice an oral micellar formulation of TY1. As the prototype for a novel class of ncRNA drugs which target cell stress, TY1 exhibits exceptional disease-modifying bioactivity in HFpEF.

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Semaglutide versus placebo in people with obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF DM randomised trials

Cited by 64 publications

References 48 publications

Left Atrial Myopathy in Heart Failure With Preserved Ejection: Don’t Raise the Roof!

Left Atrial Myopathy in Heart Failure With Preserved Ejection: Don’t Raise the Roof!

Glucagon-Like Peptide 1 Receptor Agonist Use in Hospital: A Multicentre Observational Study

Intravenous and oral administration of the synthetic RNA drug, TY1, reverses heart failure with preserved ejection fraction in mice

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