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

Diabetes Care. 2018 Jul;41(7):1510-1515. doi: 10.2337/dc18-0109. Epub 2018 May 30.

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 = 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.

Trial registration: ClinicalTrials.gov NCT00968708.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / blood*
  • Acute Coronary Syndrome / diagnosis*
  • Acute Coronary Syndrome / etiology
  • Aged
  • Biomarkers / analysis
  • Biomarkers / blood
  • Blood Chemical Analysis / methods*
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / diagnosis*
  • Diabetes Mellitus, Type 2 / therapy
  • Diabetic Angiopathies / blood
  • Diabetic Angiopathies / diagnosis
  • Diabetic Angiopathies / therapy
  • Double-Blind Method
  • Equivalence Trials as Topic
  • Female
  • Hospitalization
  • Humans
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / analysis
  • Natriuretic Peptide, Brain / blood*
  • Peptide Fragments / analysis
  • Peptide Fragments / blood*
  • Piperidines / therapeutic use
  • Prognosis
  • Uracil / analogs & derivatives
  • Uracil / therapeutic use

Substances

  • Biomarkers
  • Peptide Fragments
  • Piperidines
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • Uracil
  • alogliptin

Associated data

  • ClinicalTrials.gov/NCT00968708