LAUSR

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 (<400, 400-999, 1000-1999, 2000-2999, and >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.