PERSPECTIVES
- •COMPETENCY IN MEDICAL KNOWLEDGE: This prospectively planned secondary analysis of the VICTORIA study preselected 5 biomarkers measured at baseline and 16 weeks thought to reflect the potentially beneficial nonvasodilatory mechanisms of action of vericiguat, a sGC stimulator, in patients with heart failure with a reduced ejection fraction.
- •COMPETENCY IN PATIENT CARE: In this population with a high event rate, baseline hs-cTnT, GDF-15, and IL-6 were prognostic in a comprehensive adjustment model inclusive of NT-proBNP levels.
- •TRANSLATIONAL OUTLOOK: This study is one of the first to identify that progressively lower baseline levels of hs-cTnT could distinguish participants deriving increasing benefit from a specific heart failure treatment to decrease cardiovascular death.
Abstract
Background
Circulating biomarkers may be useful in understanding prognosis and treatment efficacy
in heart failure with reduced ejection fraction. In the VICTORIA (Vericiguat Global
Study in Subjects with Heart Failure with Reduced Ejection Fraction) trial, vericiguat,
a soluble guanylate cyclase stimulator, decreased the primary outcome of cardiovascular
death or heart failure hospitalization in heart failure with reduced ejection fraction.
We evaluated biomarkers of cardiac injury, inflammation, and renal function for associations
with outcomes and vericiguat treatment effect.
Methods and Results
High-sensitivity cardiac troponin T (hs-cTnT), growth differentiation factor-15 (GDF-15),
interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), and cystatin C
were measured at baseline and 16 weeks. Associations of biomarkers with the primary
outcome and its components were estimated. Interaction with study treatment was tested.
Changes in biomarkers over time were examined by study treatment. One or more biomarkers
were measured in 4652 (92%) of 5050 participants at baseline and 4063 (81%) at 16
weeks. After adjustment, higher values of hs-cTnT, growth differentiation factor-15,
and interleukin-6 were associated with the primary outcome, independent of N-terminal
pro-B-type natriuretic peptide. Higher hs-cTnT values were associated with a hazard
ratio per log standard deviation of 1.21 (95% confidence interval 1.14–1.27). A treatment
interaction with vericiguat was evident with hs-cTnT and cardiovascular death (P = .04), but not HF hospitalization (P = .38). All biomarkers except cystatin C decreased over 16 weeks and no relationship
between treatment assignment and changes in biomarker levels was observed.
Conclusions
hs-cTnT, growth differentiation factor-15, and interleukin-6 levels were associated
with risk of the primary outcome in VICTORIA (Vericiguat Global Study in Subjects
with Heart Failure with Reduced Ejection Fraction). Uniquely, lower hs-cTnT was associated
with a lower rate of cardiovascular death but not HF hospitalization after treatment
with vericiguat.
Graphical Abstract
Graphical Abstract
Key Words
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Article info
Publication history
Published online: January 09, 2023
Accepted:
December 12,
2022
Received in revised form:
December 12,
2022
Received:
September 2,
2022
Publication stage
In Press Journal Pre-ProofFootnotes
Clinical Trial Registration: Clinicaltrials.gov (NCT02861534).
Identification
Copyright
© 2023 Elsevier Inc. All rights reserved.
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- Leveraging biomarkers for precision medicine in heart failureJournal of Cardiac Failure
- PreviewOver the past decade, the number of therapies for heart failure (HF) with clinical trial evidence of benefit has multiplied. Physicians treating HF today are faced with the challenges of selecting and prioritizing among drugs to optimize therapy for each patient. The current paradigm centers around four first-line therapies—beta blockers, angiotensin-receptor-neprilysin inhibitors, mineralocorticoid-receptor antagonists and sodium–glucose cotransporter 2 (SGLT2) inhibitors—that showed the largest relative effects in broad patient populations (1).
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