Heart failure & cardiomyopathiesSecondary analysis

Targeted Metabolomic Profiling of Dapagliflozin in Heart Failure With Preserved Ejection Fraction

JACC Heart FailPublished

  • Secondary analysis of the PRESERVED-HF randomised trial
  • placebo-controlled
  • targeted metabolomic profiling

Authors' conclusion

Leveraging targeted metabolomics in a placebo-controlled SGLT2i trial of HFpEF, dapagliflozin did not alter systemic metabolic as reflected by circulating metabolites, in contrast with reported effects in HF with reduced ejection fraction.

Study context

Population
Patients with HF with preserved ejection fraction (HFpEF) in a 12-week trial; mean age 70 ± 11 years, 58% female, 29% Black
Participants
293 patients
Comparison
Dapagliflozin vs placebo
Primary endpoint
Changes in 64 targeted metabolites (12 PCA-derived metabolite factors)
Follow-up
12 weeks

Primary result

As reported in the abstract

12 PCA-derived metabolite factors
  • No significant differences in 12 principal components analysis (PCA)-derived metabolite factors between arms, incl. ketone, fatty acid or branched-chain amino acid (BCAA) pathways

Further findings

Metabolite changes vs changes in study endpoints (arms combined)

Changes in BCAAs and branched-chain ketoacids negatively associated with changes in NT-proBNP
Changes in medium-/long-chain acylcarnitines positively associated with NT-proBNP changes and negatively with 6-minute walk distance changes
Changes in ketones negatively associated with weight changes
  • without treatment interaction

Original publication

Targeted Metabolomic Profiling of Dapagliflozin in Heart Failure With Preserved Ejection Fraction. JACC Heart Fail. Published 17 April 2024. doi:10.1016/j.jchf.2024.02.018

Summarised from the published abstract; every number is checked against it