1. Sequential Evaluation of NT-proBNP in Heart Failure: Insights Into Clinical Outcomes and Efficacy of Vericiguat
- Author
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Armstrong, Paul W., Zheng, Yinggan, Troughton, Richard W., Lund, Lars H., Zhang, Jian, Lam, Carolyn S.P., Westerhout, Cynthia M., Blaustein, Robert O., Butler, Javed, Hernandez, Adrian F., Roessig, Lothar, O'Connor, Christopher M., Voors, Adriaan A., Ezekowitz, Justin A., and Cardiovascular Centre (CVC)
- Subjects
N-terminal pro-B-type natriuretic peptide (NT-proBNP) ,natriuretic peptide ,vericiguat ,heart failure - Abstract
Background: The effect of vericiguat on sequential N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels and influence of this relationship on clinical outcomes is unknown. Objectives: This study assessed the relationship between changes in NT-proBNP and the primary outcome (cardiovascular death or heart failure hospitalization); evaluated the effect of vericiguat on changes in NT-proBNP; and explored the association between the efficacy of vericiguat and changes in NT-proBNP. Methods: NT-proBNP was measured at randomization and at 16, 32, 48, and 96 weeks in 4,805 of 5,050 patients. The association between NT-proBNP change at week 16 and the primary outcome was assessed. The relationship between changes in NT-proBNP and the primary outcome according to treatment group was assessed by using joint modeling and mediation analysis. Results: A significant and sustained decline in NT-proBNP levels was seen in both treatment groups. After week 16, NT-proBNP levels decreased more with vericiguat vs placebo (any reduction: odds ratio [OR]: 1.45 [95% CI: 1.28-1.65]; P < 0.001; ≥50% reduction: OR: 1.27 [95% CI: 1.10-1.47]; P = 0.001) and were less likely to increase (≥20% increase: OR: 0.68 [95% CI: 0.59-0.78]; P < 0.001; ≥50% increase: OR: 0.70 [95% CI: 0.59-0.82]; P < 0.001). The treatment effect related to serial NT-proBNP on the primary composite outcome was HR: 0.96 (95% CI: 0.95-0.99) at week 16, which increased to HR: 0.90 (95% CI: 0.85-0.96) at week 48; the average extent of mediation of the composite outcome related to NT-proBNP was 45%. Conclusions: In patients with worsening HFrEF, vericiguat significantly decreased NT-proBNP levels compared with placebo. This change appeared associated with a modest relative improvement in the primary outcome of cardiovascular death or heart failure hospitalization.
- Published
- 2022