What are the findings of the PARADIGM-HF and PARAMOUNT trials related to the efficacy of brain natriuretic peptide (BNP) assays?

Updated: Jan 08, 2018
  • Author: Donald Schreiber, MD, CM; Chief Editor: Erik D Schraga, MD  more...
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Answer

In July 2015, the FDA approved the combination tablet sacubitril/valsartan (Ernesto) to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with CHF (NYHA class II-IV) and reduced ejection fraction. [47] The combination drug is the first approved agent in the angiotensin receptor-neprilysin inhibitor (ARNI) class and consists of the angiotensin-receptor blocker valsartan affixed to the neprilysin inhibitor sacubitril. The cardiovascular and renal effects of sacubitril’s active metabolite (LBQ657) in heart failure are attributed to the increased levels of peptides that are degraded by neprilysin (eg, natriuretic peptide). Administration results in increased natriuresis, increased urine cGMP, and decreased plasma mid-regional proatrial natriuretic peptide (MR-proANP) and NT-proBNP.

The approval was based on the Prospective Comparison of ARNI with ACE-I to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial. [48] PARADIGM-HF studied 8442 patients with CHF treated with either valsartan/sacubitril or enalapril. The combination significantly reduced cardiovascular death or heart-failure hospitalizations (the study's primary end point) by 20% compared with treatment with enalapril alone. All-cause mortality, a secondary end point, was also significantly reduced with the ARNI when compared with enalapril.

The Prospective Comparison of ARNI with ARB on Management of Heart Failure with Preserved Ejection Fraction (PARAMOUNT) trial compared reduction of NP-proBNP levels with sacubitril plus valsartan and valsartan alone over 12 weeks in 149 patients with LVEF of 45% or greater. Sacubitril/valsartan reduced NT-proBNP levels to a significantly greater extent (783 pg/mL at baseline and 605 pg/mL at 12 weeks) compared with valsartan alone (862 pg/mL at baseline and 835 pg/mL at 12 weeks). [49]


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