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sGC stimulator beneficial in HFrEF patients up to NT-proBNP levels of 8000 pg/mL
Literature - Ezekowitz JA, O’Connor CM, Troughton RW, et al. - JACC Heart Fail. 2020; 8(11):931-939. doi: 10.1016/j.jchf.2020.08.008.

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 [1].

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).

Main results

  • 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.


1. Armstrong PW, Pieske B, Anstrom KJ, et al. Vericiguat in patients with heart failure and reduced ejection fraction. N Engl J Med 2020;382:1883-93.

Find this article online at JACC Heart Fail.

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Schedule24 May 2024