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 Adrian A, Ezekowitz Justin A
Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada.
Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada.
JACC Heart Fail. 2022 Sep;10(9):677-688. doi: 10.1016/j.jchf.2022.04.015. Epub 2022 Jul 6.
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.
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.
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.
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%.
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. (Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction [VICTORIA]; NCT02861534).
维立西呱对序贯N末端B型利钠肽原（NT-proBNP）水平的影响以及这种关系对临床结局的影响尚不清楚。
本研究评估NT-proBNP变化与主要结局（心血管死亡或心力衰竭住院）之间的关系；评估维立西呱对NT-proBNP变化的影响；并探讨维立西呱疗效与NT-proBNP变化之间的关联。
在5050例患者中的4805例患者随机分组时以及第16、32、48和96周时测量NT-proBNP。评估第16周时NT-proBNP变化与主要结局之间的关联。采用联合建模和中介分析评估NT-proBNP变化与治疗组主要结局之间的关系。
两个治疗组的NT-proBNP水平均出现显著且持续下降。第16周后，与安慰剂相比，维立西呱组的NT-proBNP水平下降幅度更大（任何降幅：比值比[OR]：1.45[95%CI：1.28-至1.65]；P<0.001；降幅≥50%：OR：1.27[95%CI：1.10-1.47]；P=0.001），且升高的可能性更小（升幅≥20%：OR：0.68[95%CI：0.59-0.78]；P<0.001；升幅≥50%：OR：0.70[95%CI：0.59-0.82]；P<0.001）。第16周时，与系列NT-proBNP相关的治疗效果对主要复合结局的风险比（HR）为0.96（95%CI：0.95-0.99），至第48周时升至HR：0.90（95%CI：0.85-0.96）；与NT-proBNP相关的复合结局的平均中介程度为45%。
在射血分数降低的心力衰竭（HFrEF）病情恶化患者中，与安慰剂相比，维立西呱显著降低NT-proBNP水平。这一变化似乎与心血管死亡或心力衰竭住院这一主要结局的适度相对改善相关。（射血分数降低的心力衰竭患者维立西呱全球研究[VICTORIA]；NCT02861534）
