Barry A. Borlaug, MD: Impact of Tirzepatide on Cardiorenal End-Organ Damage in HFpEF

Tirzepatide lowered circulatory pressure-volume overload and reduced end-organ damage in the kidney and heart in patients with heart failure with preserved ejection fraction (HFpEF) and obesity, according to data from the SUMMIT trial.

Presented as featured science at the American Heart Association (AHA) Scientific Sessions 2024, these data build upon the known benefit of tirzepatide, a long-acting glucose-dependent insulinotropic polypeptide receptor and glucagon-like peptide-1 receptor agonist (GLP-1 RA), for the treatment of obesity-related HFpEF.

“I think it ties together a lot of the pathophysiologic components that we think are very important in obesity-related HFpEF, and tirzepatide seems to be working through many of these different pathways, some of them hemodynamic and volume-loading and [others] related to inflammation,” presenting investigator Barry A. Borlaug, MD, Mayo Clinic, told HCPLive.

The double-blind SUMMIT trial randomized 731 individuals with NYHA Class II-IV heart failure, an EF of ≥50%, and body mass index (BMI) ≥30 kg/m2 to tirzepatide (n = 364) or placebo (n = 367). Tirzepatide was titrated to a maximum weekly tolerated dose of up to 15 mg subcutaneously.

For the analysis, Borlaug and colleagues collected data on blood pressure, anthropometrics, estimated plasma volume, and blood samples at baseline and 52 weeks, to determine biomarkers of cardiorenal function in all patients. Primary results from SUMMIT showed tirzepatide lowered the risk of cardiovascular death or worsening heart failure (hazard ratio [HR], 0.62; 95% CI, 0.41–0.95; P = .026).

Trial participants exhibited borderline hypertension (systolic blood pressure [SBP], ~128 mmHg), volume expansion (estimated plasma volume, ~3.3 L), chronic kidney disease (urine albumin/creatinine ratio [UACR], ~2.8 g/mol), and subclinical myocardial injury (troponin T, ~11 ng/L).

Compared with placebo, tirzepatide treatment reduced SBP by ~6 mmHg (95% CI, –8 to –4; P <.001) at 24 weeks and by –5 mmHg (95% CI, –7 to –3; P <.001) at 52 weeks, respectively. Tirzepatide also decreased the estimated plasma volume by ~0.32 L (95% CI, –0.36 to –0.27; P <.001) at 52 weeks.

At the same time, tirzepatide achieved an increase in eGFR at 52 weeks (~1.85 ml/min/1.73 m2; 95% CI, 0.19–3.51; P = .029), decreases in microalbuminuria at 24 weeks (–25.0%; 95% CI, –36 to –13; P <.001) and 52 weeks (–15%; 95% CI, –28 to 0.1; P = .051), and a reduction in troponin T at 24 weeks (–9.8%; 95% CI, –16.0 to –3.3; P = .004) and 52 weeks (–10.4%; 95% CI, –16.7 to –3.6; P = .003).

“I think we need to be looking to use these drugs, these incretin-based drugs, more frequently, including tirzepatide, for the treatment of people with obesity-related HFpEF,” Borlaug told HCPLive.

Disclosures: Borlaug reports relevant disclosures with Amgen, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, and others.

Reference

_{Borlaug BA. Effects of Tirzepatide on Cardiorenal End-Organ Damage in Heart Failure and Preserved Ejection Fraction: Insights from the SUMMIT trial. Presented at the American Heart Association (AHA) Scientific Sessions 2024. Chicago, Illinois. November 16-18, 2024.}