Physicians' Academy for Cardiovascular Education

Changes in NT-proBNP levels identify T2DM patients at high risk for major CV events

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

Literature - Jarolim P, White WB, Cannon CP, et al. - Diab Care 2018; published online ahead of print

Introduction and Methods

The cardiovascular (CV) safety of alogliptin, a dipeptidyl peptidase 4 (DPP-4) inhibitor indicated for the treatment of type 2 diabetes mellitus (T2DM) patients, has been assessed in the Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care (EXAMINE) study [1,2].

T2DM patients are at increased risk of heart failure (HF), and biomarkers such as B-type natriuretic peptide (BNP) and the N-terminal part of the precursor molecule proBNP (NT-proBNP) have prognostic value with regard to HF and major CV events [3,4]. In this analysis of the EXAMINE study, the prognostic implications of changes in natriuretic peptide concentration over time were assessed, in patients with T2DM and ischemic heart disease. Moreover, the changes in BNP and NT-proBNP with alogliptin were evaluated.

EXAMINE was a double-blind, placebo-controlled, non-inferiority trial that recruited 5,380 T2DM patients with a recent acute coronary syndrome (ACS), who were randomized to receive either alogliptin or placebo. Median follow-up in EXAMINE was 597 days (IQR: 361–792 days). The primary end point was the composite of CV death, non-fatal myocardial infarction, or non-fatal stroke. For this analysis, the main endpoints of interest were CV death or hospitalization for HF.

Main results


In T2DM patients with a recent ACS, NT-proBNP concentrations at baseline and at 6 months identified those at high risk for adverse CV outcomes, including HF. Absolute and categorical increases of NT-proBNP levels between baseline and 6 months were associated with adverse CV outcomes. These data point at the potential value of serial monitoring of natriuretic peptides in patients with T2DM to identify those at high risk for CV events, including HF, potentially to give them specific treatment to lower this risk.


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