Relation between therapy-induced changes in natriuretic peptide levels and long-term therapeutic effects on mortality in patients with heart failure and reduced ejection fraction

Abstract

Aims: To assess whether natriuretic peptides (NPs) can be used to reliably predict long-term therapeutic effect on clinical outcomes for patients with heart failure and reduced ejection fraction (HFrEF).

Methods and results: HFrEF intervention trials with mortality data were identified. Subsequently, we identified trials assessing therapy-induced changes in NPs. We assessed the correlation between the average short-term placebo-corrected drug or device effect on NPs and the longer-term therapeutic effect on clinical outcomes. Of 35 distinct therapies with an identifiable mortality result (n = 105 062 patients), 20 therapies had corresponding data on therapeutic effect on NPs. No correlation was observed between therapy-induced placebo-corrected change in brain natriuretic peptide or N-terminal pro-brain natriuretic peptide and therapeutic effect on all-cause mortality (ACM) (Spearman r = -0.32, P = 0.18 and r = -0.20, P = 0.47, respectively). There was no correlation between therapy-induced placebo-corrected per cent change in NP and intervention effect on ACM or ACM-heart failure hospitalizations (r = -0.30, P = 0.11 and r = 0.10, P = 0.75, respectively).

Conclusions: Short-term intervention-induced changes in NP levels are not reliable predictors of therapeutic long-term effect on mortality or morbidity outcomes for patients with HFrEF.

Keywords: Biomarkers; Heart failure with reduced ejection fraction; Natriuretic peptides; Surrogate endpoints.