Physicians' Academy for Cardiovascular Education

Greatest treatment effect of sGC stimulator in worsening HFrEF with NT-proBNP <75th percentile

Vericiguat and NT-proBNP in patients with heart failure with reduced ejection fraction: analyses from the VICTORIA trial

Literature - Senni M, Lopez-Sendon J, Cohen-Solal A, et al. - ESC Heart Fail. 2022 Jul 26. doi: 10.1002/ehf2.14050

Introduction and methods

Background

Increased NT-proBNP levels are associated with worse outcomes in patients with HF [1]. Previously, the primary analysis of the VICTORIA trial showed that the sGC stimulator vericiguat reduced the risk of time to cardiovascular death or first HF hospitalization in patients with HF and that this result was generally consistent across subgroups. However, a post hoc analysis of the VICTORIA trial showed that the treatment effect of vericiguat, compared with placebo, was greatest in patients with NT-proBNP levels <8000 pg/ml at randomization [2]. To better understand this discrepancy in treatment effect, another post hoc analysis was performed.

Aim of the study

This post-hoc analysis of the VICTORIA trial compared the treatment effect of vericiguat in chronic HF between patients with NT-proBNP levels in the combined lower three baseline quartiles (Q1-Q3) and those with NT-proBNP levels in the upper baseline quartile (Q4).

Methods

The VICTORIA trial is a randomized, double-blind, placebo-controlled phase 3 study in which 5050 patients with worsening HFrEF and elevated BNP or NT-proBNP levels within 6 months after a HF event were randomized to receive vericiguat (10 mg once daily) or placebo, in addition to guideline-based treatment. Only data from 4805 participants (95.1%) whose NT-proBNP levels were known at baseline were used in this post hoc analysis. Patients were divided into two groups: one group had NT-proBNP levels in Q1-Q3, the other group had NT-proBNP levels in Q4. The NT-proBNP quartiles were pre-specified subgroups; however, the analysis of Q1-Q3 versus Q4 was post hoc.

Outcomes

The primary outcome was the composite endpoint of time to cardiovascular death or first HF hospitalization. Safety was reported by NT-proBNP subgroup and overall. The investigators were particularly interested in the following (serious) adverse events (AEs): symptomatic hypotension, syncope, and hepatic events.

Main results

Primary outcome

Safety

Conclusion

This post hoc analysis of the VICTORIA trial suggests that the beneficial effects of vericiguat are greatest in patients with worsening HFrEF and NT-proBNP levels <75th percentile. NT-proBNP can thus potentially help identify patients with worsening HFrEF in whom the treatment effect of vericiguat is expected to be greatest.

References

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Find this article online at ESC Heart Fail.

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