Introduction and methods

Effects of Sacubitril/Valsartan on N-Terminal Pro-B-Type Natriuretic Peptide in Heart Failure with Preserved Ejection Fraction

Presented at ACC.20 by Jonathan W Cunningham (Boston, MA, USA)

In the PARAGON-HF trial, the effect of the angiotensin receptor-neprilysin inhibitor sacubitril/valsartan was evaluated compared to valsartan alone. Sacubitril targets the vasoactive peptide system by inhibition of neprilysin, and valsartan targets the renin angiotensin system. The PARAGON-HF trial included 2730 patients ≥50 years, EF ≥45, elevated natriuretic peptides and structural heart disease. Minimum NT-proBNP levels for inclusion were: >200 pg/mL with HF hospitalization, >300 pg/mL without hospitalization, or a 3-fold increase of those cutoff levels in AF patients. Patients were randomized to 97/103 mg sacubitril/valsartan bid or 160 mg valsartan bid and median follow-up was 27 months. In the main trial, the primary endpoint of total HF hospitalizations and CV death just missed statistical significance.

This study investigated the relationship between NT-proBNP and outcomes in HFpEF patients and the effect of sacubitril/valsartan on NT-proBNP levels after week 48. For the first part of this study, patients were divided into quartiles based on baseline NT-proBNP levels (Q1: <464, n=1190; Q2: 465-911, n=1189; Q3: 912-1613, n=1189; Q4: 1617-31,5222, n=1190).

Main results

• Baseline NT-proBNP strongly predicts outcome of HF hospitalization and CV death (Q1: 8.7 events per 100 PY, Q2: 11.5 per 100 PY, Q3: 12.2 per 100 PY, Q4: 23.5 per 100 PY).
• Presence of AF modifies NT-proBNP associated risk of outcomes (P-interaction<0.001) (risk was lower in those with AF for any given NT-proBNP level).
• When comparing the relationship of NT-proBNP with outcomes between obese and non-obese patients, those with obesity and low NT-proBNP levels had a moderate risk of outcomes (P-interaction<0.001).
• The effect of sacubitril/valsartan on outcomes was independent of baseline NT-proBNP levels (analyzed per quartiles).
• Treatment with sacubitril/valsartan resulted in reduction of NT-proBNP of 19% compared to valsartan (P<0.001). This reduction was consistent in subgroup analyses (men vs. women, higher LVEF vs. lower LVEF).
• Decrease in NT-proBNP was associated with lower event rate. In those with a decrease in NT-proBNP, there were 23% fewer events compared to those with increased NT-proBNP levels.

Conclusion

This subanalysis of the PARAGON-HF trial showed that use of sacubitril/valsartan resulted in a 19% reduction of NT-proBNP levels compared to valsartan. Furthermore, baseline NT-proBNP levels were associated with outcome of HF hospitalization and CV death in HFpEF patients.

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