Significant NT-proBNP reduction with sacubitril/valsartan in HF patients with ejection fraction >40%

The PARAGLIDE-HF trial revealed that therapy with sacubitril/valsartan is also beneficial for patients with an ejection fraction (EF)>40%. Therapy with sacubitril/valsartan led to greater reductions of NT-proBNP levels compared with valsartan monotherapy.

The PARAGON-HF (NCT01920711) trial excluded patients with decompensated heart failure, but a post-hoc analysis suggested a larger benefit with sacubitril/valsartan in those recently hospitalised [1]. It remained unknown whether initiation of sacubitril/valsartan is safe and effective in patients with EF >40% stabilised after a worsening heart failure (HF) event. To evaluate this, the current PARAGLIDE-HF study (NCT03988634) analysed 466 patients with HF with or without preserved EF (EF>60%) [2]. All study participants had a recent event of HF worsening in-hospital or within 30 days of HF hospitalisation. The average age was 70 years, 52% were women, and 22% were Black. They were randomised to treatment with sacubitril/valsartan (n=233) or valsartan alone (n=233). The primary endpoint was the time-averaged proportional change in NT-proBNP levels from baseline to weeks 4 and 8. Prof. Robert Mentz (Duke University Medical Center, NC, USA) presented the results.

The trial met its primary endpoint: a 15% greater reduction was seen in the NT-proBNP concentrations with sacubitril/valsartan compared with valsartan alone through 8 weeks (ratio of change 0.85; 95% CI 0.73–0.99; P=0.049). Moreover, a beneficial effect of sacubitril/valsartan was also seen in a secondary composite hierarchical outcome of (a) time to cardiovascular death, (b) number and timing of HF hospitalisations, (c) number and timing of urgent HF visits and (d) time-averaged proportional change in NT-proBNP from baseline to weeks 4 and 8. The hierarchical outcome favoured sacubitril/valsartan but was not significant (unmatched win ratio 1.19; 95% CI 0.93–1.52; P=0.16). “Each component [of the composite endpoint] favoured sacubitril/valsartan,” Prof. Mentz said. Another positive effect of sacubitril/valsartan was the reduction of worsening renal function (odds ratio 0.61; 95% CI 0.40–0.93).

Pre-specified subgroup analyses in patients with EF below normal (EF≤60%) showed that patients with EF>40–≤60 had a 22% greater reduction of NT-proBNP with sacubitril/valsartan compared with those with an EF>60%. “There is a heterogeneous treatment effect in the below-normal ejection fraction group,” Prof. Mentz commented.

He explained that these results, particularly in light of similar findings from PARAGON-HF, provide additional support for a potential treatment benefit of sacubitril/valsartan in HF patients with an EF>40%. Therefore, these results may influence future guidance for these patients, regardless of HF chronicity (i.e. acute and chronic versus de novo HF) and treatment setting.

1. 1. Vaduganathan M, et al. J Am Coll Cardiol 2020;75:245–54.
   2. Mentz R. PARAGLIDE-HF: Sacubitril/Valsartan versus valsartan on changes in NTproBNP, safety, and tolerability in patients with EF>40% stabilized after a WHF event. Session Late breaking clinical trials: medical therapy, Heart Failure 2023, 20–23 May, Prague, Czechia.

 

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Posted on 24 May, 2023