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

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 ( < 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 ( < 0.001) or developed high NT-proBNP at 6 months ( < 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 ( = 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.