Biomarkers hs-cTnT, GDF-15 and IL-6 related to adverse CV outcomes in HFrEF
Assessment of biomarkers of myocardial injury, inflammation, and renal function in heart failure with reduced ejection fraction: the VICTORIA biomarker substudy
Introduction and methods
Background
Circulating biomarkers of myocardial injury, hemodynamic stress, systemic inflammation or renal function are related to adverse cardiovascular outcomes in patients with HFrEF [1-6]. Previously, the VICTORIA trial showed that the soluble guanylate cyclase (sGC) stimulator vericiguat reduces the risk of cardiovascular death or first hospitalization for HF in patients with HFrEF [7]. The influence of circulating biomarkers for myocardial injury, inflammation or renal function on cardiovascular outcomes in patients with HfrEF was further investigated in the VICTORIA trial.
Aim of the study
This substudy of the VICTORIA trial examined the relationship between serum levels of biomarkers of myocardial injury, inflammation or renal function, and the time to cardiovascular death or first hospitalization for HF and vericiguat’s treatment effect.
Methods
The VICTORIA trial is a randomized, double-blind phase 3 study in which 5050 patients with HFrEF and an LVEF <45%, NYHA class II-IV symptoms and elevated BNP or NT-proBNP levels within 6 months after HF hospitalization or within 3 months of receipt of IV diuretics were randomized to receive vericiguat or placebo. In this substudy of the VICTORIA trial, only data from 4063 participants (81%) in whom serum levels of at least one of the following biomarkers of myocardial injury, inflammation or renal function had been measured at baseline and after 16 weeks were used: hs-cTnT, GDF-15, IL-6, hs-CRP, and cystatin C.
Outcomes
The primary outcome was a composite of the time to cardiovascular death or first hospitalization for HF, and also the individual components of the primary outcome were studied.
Main results
- After adjusting for NT-proBNP levels at baseline, among other variables, higher serum levels of hs-cTnT (hazard ratio (HR) per SD increase: 1.21; 95%CI: 1.14-1.27), GDF-15 (HR per SD increase: 1.19; 95%CI: 1.12-1.27) and IL-6 (HR per SD increase: 1.07; 95%CI: 1.01-1.13) were related to the primary outcome.
- In contrast, serum levels of hs-CRP (HR per SD increase: 1.03; 95%CI: 0.97-1.09) and cystatin C (HR per SD increase: 1.04; 95%CI: 0.97-1.10) were not related to the primary outcome.
- For the individual components of the primary outcome, similar HRs were found for hs-cTnT and GDF-15, but modest differences were seen for the 3 least prognostic biomarkers (IL-6, hs-CRP and cystatin C).
- For the primary outcome, no interaction was found between the serum levels of the biomarkers and the assigned treatment.
- An interaction was found between the serum levels of hs-cTnT and treatment with vericiguat for the time to cardiovascular death (P-interaction=0.04), but not for the time to first hospitalization for HF (P-interaction=0.38).
- After 16 weeks, serum levels of all biomarkers except cystatin C had decreased, with no differences between treatment groups.
Conclusion
This substudy of the VICTORIA trial shows that serum levels of biomarkers of myocardial injury, inflammation or renal function (Hs-cTnT, GDF-15 and IL-6) are related to the primary outcome, which was a composite of the time to cardiovascular death or first hospitalization for HF, in patients with HFrEF treated with vericiguat or placebo. No relation between lowering of biomarkers and vericiguat treatment was observed.
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