sGC stimulator beneficial in HFrEF patients up to NT-proBNP levels of 8000 pg/mL
N-Terminal Pro-B-Type natriuretic Peptide and Clinical Outcomes: Vericiguat Heart Failure With Reduced Ejection Fraction Study
Introduction and methods
The VICTORIA (A Study of Vericiguat in Participants With Heart Failure With Reduced Ejection Fraction) trial showed a reduction in the primary outcome of CV death or hospitalization due to HF with the soluble guanylate cyclase (sGC) stimulator vericiguat compared to placebo in patient with worsening HFreEF . A subanalysis demonstrated that patients within the highest quartile of baseline NT-proBNP (>5.314 pg/ml) appeared to have less benefit from vericiguat, while patients in the three lower baseline NT-proBNP quartiles derived greater benefit from this treatment .
The current study further assessed the NT-proBNP subgroup outcome of the VICTORIA trial on the primary and individual outcomes and explored the treatment effects of vericiguat in relation to NT-proBNP levels, using NT-proBNP as a log-transformed continuous parameter.
In the VICTORIA trial, participants with worsening chronic HF (NYHA class II to IV), LFEV <45%, elevated natriuretic peptide levels, and recent HF decompensation, were randomized (1:1) to vericiguat or placebo. Patients in sinus rhythm had to have a BNP level of ≥300 pg/ml or NT-proBNP of ≥1000 pg/ml and patients with atrial fibrillation had to have a BNP level of ≥500 pg/ml or NT-proBNP of ≥1600 pg/ml. The primary outcome was a composite of CV death or hospitalization for HF. Secondary outcomes were the individual components of the primary outcome. NT-proBNP was measured in 4805 patients, who were included in the current analysis. Cut points were estimated from the treatment effect of vericiguat across the spectrum of NT-proBNP in which the upper confidence limit did not include 1.00 (at 4000 pg/mL) and below which the point estimate of the treatment effect was <1.00 (at 8000 pg/mL).
- When NT-proBNP levels were analyzed as a continuous variable, the treatment effect of vericiguat on the primary outcome was observed up to 8000 pg/mL.
- At 4000 pg/mL NT-proBNP, the treatment effect of vericiguat on primary outcome had an HR of 0.90 (95%CI: 0.82-0.99). In those with NT-proBNP ≤4000 pg/mL, vericiguat reduced the primary endpoint compared to placebo (aHR 0.77, 95% CI:0.68-0.88).
- Also, the individual outcomes CV death and HF hospitalization were reduced by vericiguat in patients with NT-proBNP levels ≤4000 pg/ml (aHR 0.75, 95% CI:0.60-0.94 and aHR 0.78, 95% CI:0.67-0.90, respectively).
- The treatment effect by vericiguat on the primary outcomes was extended to 8000 pg/mL NT-proBNP (aHR 0.85, 95% CI:0.76-0.95), as well as for the individual endpoints CVD (aHR 0.84, 95% CI:0.71-0.99) and HF hospitalization (aHR 0.84, 95% CI:0.75-0.95). When levels >8000 pg/mL were analyzed, the treatment effect by vericiguat on outcomes was no longer evident.
High-risk HFrEF patients with NT-proBNP levels up to 8000 pg/ml in the VICTORIA trial, had a reduced risk on the primary outcome CV death and hospitalization for HF as well as individual outcomes when treated with the sGC stimulator vericiguat.