Natriuretic Peptide Plasma Concentrations and Risk of Cardiovascular Versus Non-Cardiovascular Events in Heart Failure with Reduced Ejection Fraction Insights from the PARADIGM-HF and ATMOSPHERE Trials.

2021 
ABSTRACT Background : N-terminal pro-B-type natriuretic peptide (NTproBNP) plasma concentrations are independent prognostic markers in patients with heart failure with reduced ejection fraction (HFrEF). Whether a differential risk association between NTproBNP plasma concentrations and risk of cardiovascular (CV) versus non-CV adverse events exists is not well known. Objective : To assess if there is a differential proportional risk of CV versus non CV adverse events by NTproBNP plasma concentrations. Methods : In this post hoc combined analysis of PARADIGM-HF and ATMOSPHERE trials, proportion of CV versus non-CV mortality and hospitalizations were assessed by NT-proBNP levels ( 3000 pg/ml) at baseline using Cox regression adjusting for traditional risk factors. Results : 14,737 patients with mean age of 62±8 years (24% history of atrial fibrillation [AF]) were studied. For CV deaths, the event rates per 1000 patient-years steeply increased from 33.8 in the ≤400 pg/ml group to 142.3 in the ≥3000 pg/ml group, while the non-CV death event rates modestly increased from 9.0 to 22.7, respectively. Proportion of non CV deaths decreased across the 5 NT-proBNP groups (21.1%, 18.4%, 17.9%, 17.4%, and 13.7% respectively). Similar trend was observed for non-CV hospitalizations (46.4%, 42.6%, 42.9%, 42.0%, and 36.9% respectively). These results remained similar when stratified according to presence of AF at baseline and prior HF hospitalization within last 12 months. Conclusion : The absolute CV event rates per patient years of follow up were greater and had higher stepwise increases than non-CV event rates across a broad range of NT-proBNP plasma concentrations indicating a differential risk of CV events at varying baseline NT-proBNP values. These results have implications for future design of clinical trials.
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