Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity

New England Journal of Medicine, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 16, 2024

BackgroundObesity increases the risk of heart failure with preserved ejection fraction. Tirzepatide, a long-acting agonist glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors, causes considerable weight loss, but data are lacking respect to its effects on cardiovascular outcomes.MethodsIn this international, double-blind, randomized, placebo-controlled trial, we randomly assigned, in 1:1 ratio, 731 patients failure, an fraction at least 50%, body-mass index (the kilograms divided by square height meters) 30 receive tirzepatide (up 15 mg subcutaneously once per week) or placebo for 52 weeks. The two primary end points were composite adjudicated death from worsening heart-failure event (assessed time-to-first-event analysis) change baseline weeks Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS; scores range 0 100, higher indicating better quality life).ResultsA total 364 assigned group 367 group; median duration follow-up was 104 Adjudicated occurred 36 (9.9%) 56 (15.3%) (hazard 0.62; 95% confidence interval [CI], 0.41 0.95; P=0.026). Worsening events 29 (8.0%) (14.2%) 0.54; CI, 0.34 0.85), 8 (2.2%) 5 (1.4%), respectively 1.58; 0.52 4.83). At weeks, mean (±SD) KCCQ-CSS 19.5±1.2 as compared 12.7±1.3 (between-group difference, 6.9; 3.3 10.6; P<0.001). Adverse (mainly gastrointestinal) leading discontinuation trial drug 23 (6.3%) (1.4%) group.ConclusionsTreatment led lower than improved health status obesity. (Funded Eli Lilly; SUMMIT ClinicalTrials.gov number, NCT04847557.)

Language: Английский

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Effects of tirzepatide on circulatory overload and end-organ damage in heart failure with preserved ejection fraction and obesity: a secondary analysis of the SUMMIT trial

Nature Medicine, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 17, 2024

Abstract Patients with obesity-related heart failure preserved ejection fraction (HFpEF) display circulatory volume expansion and pressure overload contributing to cardiovascular–kidney end-organ damage. In the SUMMIT trial, patients HFpEF obesity were randomized long-acting glucose-dependent insulinotropic polypeptide receptor glucagon-like peptide-1 agonist tirzepatide ( n = 364, 200 women) or placebo 367, 193 women). As reported separately, decreased cardiovascular death worsening failure. Here, in this mechanistic secondary analysis of treatment at 52 weeks, as compared placebo, reduced systolic blood (estimated difference (ETD) −5 mmHg, 95% confidence interval (CI) −7 −3; P < 0.001), estimated (ETD −0.58 l, CI −0.63 −0.52; 0.001) C-reactive protein levels −37.2%, −45.7 −27.3; 0.001). These changes coupled an increase glomerular filtration rate 2.90 ml min −1 1.73 m −2 yr , 0.94 4.86; 0.004), a decrease urine albumin–creatinine ratio 24 −25.0%, −36 −13%; 0.001; −15%, −28 0.1; 0.051), reduction N-terminal prohormone B-type natriuretic peptide weeks −10.5%, −20.7 1.0%; 0.07) troponin T −10.4%, −16.7 −3.6; 0.003). post hoc exploratory analyses, was significantly correlated pressure, microalbuminuria, improved Kansas City Cardiomyopathy Questionnaire Clinical Summary Score increased 6-min walk distance. Moreover, conclusion, volume–pressure systemic inflammation mitigated injury obesity, providing new insights into mechanisms benefit from tirzepatide. ClinicalTrials.gov registration: NCT04847557 .

Language: Английский

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Effects of Glucagon‐Like Peptide‐1 Receptor Agonists, Sodium‐Glucose Cotransporter‐2 Inhibitors, and Their Combination on Neurohumoral and Mitochondrial Activation in Patients With Diabetes

Journal of the American Heart Association, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 26, 2025

Background We investigated the effects of combined treatment with glucagon like peptide‐1 receptor agonists (GLP‐1RA) and sodium‐glucose cotransporter‐2 inhibitors (SGLT‐2i) on NT‐proBNP (N‐terminal pro‐brain natriuretic peptide), GDF‐15 (growth differentiation factor 15), MOTS‐c (mitochondrial‐derived peptide‐c) in patients type 2 diabetes (T2D) high or very cardiovascular risk. Methods studied 163 consecutive who were treated insulin (n=40), liraglutide (n=41), empagliflozin (n=42), their combination (GLP‐1RA+SGLT‐2i) (n=40) matched using propensity score analysis. measured following at baseline 4 12 months treatment: (1) NT‐proBNP, GDF‐15, MOTS‐c; (2) 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid), (3) left ventricular global longitudinal strain, atrial strain during reservoir phase, work index speckle‐tracking imaging. Results At months, GLP‐1RA, SGLT‐2i, showed a greater reduction (−43.1% versus −54.2% −56.9% −14.7%) than insulin. Only SGLT‐2i GLP‐1RA+SGLT‐2i improved MOTS‐c. provided an increase compared In all patients, was associated improvement index; decrease ABTS MOTs‐c constructive myocardial ( P <0.05). Conclusions Twelve‐month neurohumoral markers antioxidant ability each alone appear more effective mitochondrial activation. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03878706.

Language: Английский

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Mechanisms of exercise intolerance in hear-t failure with preserved ejection fraction (HFpEF)

Heart Failure Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

Language: Английский

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Heart or lungs? Why not both!

European Respiratory Journal, Journal Year: 2025, Volume and Issue: 65(2), P. 2402308 - 2402308

Published: Feb. 1, 2025

Language: Английский

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Hemodynamics of Exercise-Induced Hypertension and Relationship to Outcomes in Adults With Coarctation of the Aorta

Circulation Heart Failure, Journal Year: 2025, Volume and Issue: unknown

Published: March 5, 2025

Exercise-induced hypertension (EIH) is common in adults with coarctation of the aorta (COA), but there are limited data about hemodynamics and outcomes such patients. The purpose this study was to assess changes arterial load during exercise patients COA versus without EIH, relationship clinical outcomes. We compared Doppler-derived indices (effective elastance index, total compliance systemic vascular resistance index), disease severity (pulmonary congestion, aerobic capacity, cardiovascular biomarkers) between repaired healthy controls. EIH defined as systolic blood pressure (BP) at peak >210 mm Hg men or >190 women. In prospective cohort study, we assessed (n=41, age 43±14 years, 26 [63%] men) controls (n=41). Although both groups had similar resting BP, group higher rest, well a greater rise BP each stage exercise, leading prevalence (37% 10%; P=0.004). Compared (n=26, 63%), those rest worse cardiac dysfunction, pulmonary biomarkers remodeling, despite no significant differences BP. assessment can improve risk stratification identify who may benefit from intensification medical therapy.

Language: Английский

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Obesity and inflammation in chronic and acute heart failure

Heart Failure Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: May 3, 2025

Language: Английский

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Advances in cardiovascular pharmacotherapy. III. Sodium-glucose cotransport type 2 inhibitors, part 1: efficacy in heart failure and myocardial infarction

Journal of Cardiothoracic and Vascular Anesthesia, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

Language: Английский

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