Logo

American Heart Association

  2
  0


Final ID: 4171157

Effects of Tirzepatide on Cardiorenal End-Organ Damage in Heart Failure and Preserved Ejection Fraction: Insights from the SUMMIT trial

Abstract Body (Do not enter title and authors here): Background: Patients with obesity-related heart failure and a preserved ejection fraction (HFpEF) display circulatory pressure and volume overload, contributing to end organ kidney and myocardial damage. We hypothesized that tirzepatide (TZP), a long-acting glucose-dependent insulinotropic polypeptide receptor and glucagon-like peptide-1 receptor agonist, would reduce pressure-volume overload, and thus improve end-organ cardiorenal function in HFpEF.
Methods: In this double-blind trial, we randomly assigned 731 patients with class II-IV heart failure, ejection fraction ≥50% and body mass index (BMI) ≥30 kg/m2 to tirzepatide (titrated to a maximum tolerated dose of up to 15 mg subcutaneously weekly) (n=364) or placebo (n=367). Blood pressure (BP), anthropometrics, estimated plasma volume (PV), and blood samples were obtained at baseline and out to 52 weeks for all participants to assess biomarkers indicative of cardiorenal function.
Results: As reported separately at this meeting, tirzepatide decreased cardiovascular death or worsening heart failure (hazard ratio, 0.62; 95% CI, 0.41 to 0.95; P=0.026). At baseline, participants exhibited borderline hypertension (systolic BP ~128 mmHg), volume expansion (PV~3.3 L), and chronic kidney disease (eGFR ~65 ml/min/1.73m2), with low-grade microalbuminuria (urine albumin/creatinine ~2.8 g/mol) and subclinical myocardial injury (troponin T ~11 ng/L). As compared to placebo, treatment with tirzepatide reduced systolic BP (estimated treatment difference [ETD] at 24 weeks -6 mmHg, 95% CI -8, -4, p<.001; 52 weeks -5 mmHg, 95% CI -7, -3, p<.001) and decreased PV (ETD 52 weeks -0.32 L, 95% CI -0.36, -0.27, p<0.001). These changes were coupled with increases in eGFR at 52 weeks (ETD 1.85 ml/min/1.73m2, 95% CI 0.19, 3.51; p=0.029), decreases in microalbuminuria (ETD 24 weeks, -25.0%, 95% CI -36,-13; p<.001, 52 weeks -15%, 95% CI -28, 0.1; p=0.051), and a reduction in troponin T (ETD 24 weeks -9.8% [95%CI -16.0,-3.3], p=0.004, 52 weeks -10.4% [95% CI -16.7,-3.6], p=0.003) with tirzepatide compared to placebo.
Conclusions: Tirzepatide reduced circulatory pressure-volume overload and mitigated end organ damage in the kidney and heart in patients with HFpEF and obesity, providing new insight into the mechanisms of benefit from tirzepatide in patients with obesity-related HFpEF.
  • Borlaug, Barry  ( MAYO CLINIC , Rochester , Minnesota , United States )
  • Author Disclosures:
    Barry Borlaug: DO have relevant financial relationships ; Researcher:NIH/NHLBI:Active (exists now) ; Consultant:Imbria:Past (completed) ; Consultant:Eli Lilly:Active (exists now) ; Consultant:Edwards Lifesciences:Active (exists now) ; Consultant:Boehringer Ingelheim:Active (exists now) ; Consultant:Amgen:Active (exists now) ; Consultant:Actelion:Past (completed) ; Researcher:Tenax Therapeutics:Active (exists now) ; Researcher:Rivus:Active (exists now) ; Researcher:Novo Nordisk:Active (exists now) ; Researcher:Medtronic:Active (exists now) ; Researcher:Corvia:Active (exists now) ; Researcher:AstraZeneca:Active (exists now) ; Researcher:Axon:Active (exists now) ; Researcher:DoD:Active (exists now)
Meeting Info:

Scientific Sessions 2024

2024

Chicago, Illinois

Session Info:

Featured Science: Getting Closer to the Summit: New HFpEF Treatments

Sunday, 11/17/2024 , 08:00AM - 09:15AM

Featured Science

More abstracts on this topic:
More abstracts from these authors:
Association of transcatheter edge-to-edge repair with clinical outcomes in atrial functional mitral regurgitation

Naser Jwan, Michelena Hector, Pislaru Sorin, Massad Faysal, Scott Christopher, Borlaug Barry, Pellikka Patricia, Kennedy Austin, Simard Trevor, Enriquez-sarano Maurice, Nkomo Vuyisile

PRO: Lightening the Load: Use of GLP-1 Receptor Agonists in Heart Failure

Vaduganathan Muthiah, Borlaug Barry

You have to be authorized to contact abstract author. Please, Login
Not Available