The exploratory PROVE-HF study showed that the reduction in NT-proBNP concentration in HFrEF patients treated with Entresto (sacubitril-valsartan) was weakly yet significantly correlated with improvements in markers of cardiac volume and function at 12 months. The observed reverse cardiac remodeling may provide a mechanistic explanation for the effects of Entresto in patients with HFrEF.


Methods

PROVE-HF was a 12-month open-label, single-group, exploratory phase IV study involving 794 HFrEF patients in USA treated with Entresto (sacubitril/valsartan). At enrolment, nearly all participants had NYHA Class II (n = 558; 70.3%) or III (n = 222; 28.0%) symptoms and a typical mixture of HFrEF risk factors.

  • The primary endpoint was demonstration of the correlation  between reduced NT-proBNP levels in HFrEF patients treated with Entresto and changes in values associated with cardiac structure and function assessed by change in LVEDVI, LVESVI, LVEF, LAVI and E/e′ from baseline to 12 months.
  • A secondary endpoint was the association between the changes in concentration of NT-proBNP and cardiac remodelling from baseline to 6 months. 
  • Other secondary endpoints were the 6-month associations between the changes in concentration of NT-proBNP and cardiac remodeling in specific patient subgroups not represented in the PARADIGM-HF trial.

Results

654 of the 794 patients (82.4%) completed the study. The median NT-proBNP concentration was 816 pg/ml (interquartile range [IQR] 332-1822) at baseline and 455 pg/ml (IQR 153-1090) at 12 months (difference p<.001). 

HFrEF patients treated with Entresto achieved reduced NT-proBNP levels, suggesting a correlation with improvement in cardiac structure and function at 12 months. The change in log2-NT-proBNP concentration could be correlated with the changes in:

  • LVEF (r = -0.381 [IQR -0.448 to -0.310]; p <.001), 
  • LVEDVI (r = 0.320 [IQR 0.246 to 0.391]; p <.001), 
  • LVESVI (r = 0.405 [IQR 0.335 to 0.470]; p <.001), 
  • LAVI (r = 0.263 [IQR 0.186 to 0.338]; p <.001) and 
  • E/e’ (r = 0.269 [IQR 0.182 to 0.353]; p <.001). 

 

At 12 months, LVEF had risen from 28.2% to 37.8% (absolute difference 9.4% [95% CI, 8.8% to 9.9%], p< .001), whilst LVEDVI had fallen from 86.93 to 74.15 ml/m2 (difference -12.25 ml/m2 [IQR -12.92 to 11.58]; p< .001), and LVESVI had dropped from 61.68 to 45.46 ml/m2 (difference -15.29 ml/m2 [95% CI, -16.03 to -14.55]). LAVI and the E/e’ ratio had also declined.

Regarding the secondary endpoints, lower correlations between change in log2–NT-proBNP concentrations and remodeling indices were present at 6 months. The most frequent adverse events were hypotension (17.6%), dizziness (16.8%), hyperkalaemia (13.2%), and worsening kidney function (12.3%).


Conclusion

In the exploratory study PROVE-HF, the reduction in NT-proBNP concentration in HFrEF patients treated with Entresto (sacubitril-valsartan) was weakly yet significantly correlated with improvements in markers of cardiac volume and function at 12 months. The observed reverse cardiac remodelling may provide a mechanistic explanation for the effects of Entresto in patients with HFrEF.


Reference

  1. Januzzi JL Jr, Prescott MF, Butler J, et al on behalf of the PROVE-HF investigators. Association of change in N-terminal pro–b-type natriuretic peptide following initiation of sacubitril-valsartan treatment with cardiac structure and function in patients with heart failure with reduced ejection fraction [published online ahead of print, 2 September 2019]. JAMA. DOI:10.1001/jama.2019.12821.
Betygsätt sidan
SE2204291102 (29 april 2022)
×

Ask Speakers

×

Medical Information Request