Serial Measurement of Natriuretic Peptides and Cardiovascular Outcomes in Patients With Type 2 Diabetes in the EXAMINE trial

Abstract

OBJECTIVE Patients with type 2 diabetes are at increased risk of developing heart failure (HF). Enhanced recognition of patients at risk for HF would help guide therapeutic decisions. RESEARCH DESIGN AND METHODS We investigated the prognostic implications of changes in N-terminal B-type natriuretic peptide (NT-proBNP) concentration in patients with type 2 diabetes and ischemic heart disease who were enrolled in the Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care (EXAMINE) trial, a phase 3b trial of alogliptin, a dipeptidyl peptidase 4 (DPP-4) inhibitor. Patients with type 2 diabetes and a recent acute coronary syndrome event were eligible. NT-proBNP was measured at baseline and 6 months. Cardiovascular (CV) death or hospitalization for HF was the end point of principal interest for this analysis. RESULTS We observed a strong graded relationship between increasing baseline and 6-month NT-proBNP concentration and the incidence of major CV events (P < 0.001). After adjusting for potential confounders, NT-proBNP at baseline was independently associated with the development of major CV events, in particular hospitalization for HF. Patients who had persistently high NT-proBNP (P < 0.001) or developed high NT-proBNP at 6 months (P < 0.001) were at a significantly higher risk for CV death/HF than those in whom NT-proBNP remained low at both time points or who had a high NT-proBNP value at baseline that subsequently declined to the low category. Absolute changes in NT-proBNP by 6 months were also strongly associated with subsequent outcomes. Treatment with a DPP-4 inhibitor did not meaningfully alter NT-proBNP concentrations (P 5 0.20). CONCLUSIONS Serial monitoring of NT-proBNP in patients with type 2 diabetes and ischemic heart disease may be useful for identifying patients at highest risk for HF.