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Reduced NT-proBNP in HFpEF with sacubitril/valsartan

Presented By
Prof. Burkert Pieske, Charité University Medicine Berlin, Germany
ESC 2020
Phase 3, PARALLAX study


Although sacubitril/valsartan was associated with significant reductions in N-terminal pro-b-type natriuretic peptide (NT-proBNP) in patients with heart failure with preserved ejection fraction (HFpEF) compared with individual RAAS blockade at 12 weeks, no significant difference in 6-minute walk distance or secondary endpoints were found in the phase 3 PARALLAX study [1].

Previously, the PARAGON-HF trial showed that sacubitril/valsartan improves morbidity and mortality outcomes of patients with HFpEF [2]. The PARALLAX study aimed to build on these previous clinical data by assessing the effects of sacubitril/valsartan in heart failure patients (n=2,572) with an ejection fraction >40%, evidence of left ventricular hypertrophy or left atrial enlargement, elevated NT-proBNP, and optimised treatment of comorbidities [1]. The PARALLAX study also compared sacubitril/valsartan to individualised therapy but with a different co-primary endpoint. While PARAGON-HF assessed a composite of hospitalisation for heart failure and cardiovascular death, PARALLAX assessed the biomarker NT-proBNP and 6-minute walk test, since loss of exercise capacity is a key indicator of heart failure.

Results of the PARALLAX study were presented by principal investigator Prof. Burkert Pieske (Charité University Medicine Berlin, Germany). At 12 weeks, sacubitril/valsartan was associated with a 16% greater reduction in NT-proBNP level compared with individualised medical therapy, including the angiotensin-converting enzyme (ACE) inhibitor enalapril, the angiotensin receptor blocker valsartan, or placebo (adjusted geometric mean ratio 0.84; P<0.0001; see Figure). At week 24, no significant difference was observed in the second co-primary endpoint, the 6-minute walk distance (adjusted mean difference -2.5 m; P=0.42). In accordance with this, there was also no significant difference in secondary endpoints, i.e. change of Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary scores (least square means difference 0.52; P=0.48) or NYHA class (OR 1.01; P=0.93), between the study arms at week 24.

Figure: Primary outcomes of PARALLAX [1]

IMT, individualised medical therapy; NT-proBNP, N-terminal pro-b-type natriuretic peptide; S/V, sacubitril/valsartan.

Post-hoc and exploratory analyses

A post-hoc analysis of the PARALLAX trial, comparing data from the study drug and placebo groups, showed that patients in the sacubitril/valsartan group had a 51% reduced risk of first hospitalisation due to heart failure at 24 weeks (HR 0.49; P=0.005). Also, the composite endpoint of time to death due to heart failure or heart failure hospitalisation in days was in favour of the study drug (HR 0.64; P=0.034).

However, a prespecified exploratory analysis of renal impact suggested sacubitril/valsartan was associated with a decline in estimated glomerular filtration rate (eGFR) compared with individualised medical therapy over 24 weeks (adjusted mean difference 1.10 mL/min/1.73 m2).


    1. Pieske B. PARALLAX: Sacubitril/valsartan versus individualized RAAS blockade in patients with HFpEF. Hot Line 2 session, ESC Congress 2020, 30 Aug.
    2. Solomon SD, et al. N Engl J Med 2019; 381:1609-1620.


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