PONTIAC (NT-proBNP selected prevention of cardiac events in a population of diabetic patients without a history of cardiac disease): a prospective randomized controlled trial

J Am Coll Cardiol. 2013 Oct 8;62(15):1365-72. doi: 10.1016/j.jacc.2013.05.069. Epub 2013 Jun 27.


Objectives: The study sought to assess the primary preventive effect of neurohumoral therapy in high-risk diabetic patients selected by N-terminal pro-B-type natriuretic peptide (NT-proBNP).

Background: Few clinical trials have successfully demonstrated the prevention of cardiac events in patients with diabetes. One reason for this might be an inaccurate selection of patients. NT-proBNP has not been assessed in this context.

Methods: A total of 300 patients with type 2 diabetes, elevated NT-proBNP (>125 pg/ml) but free of cardiac disease were randomized. The "control" group was cared for at 4 diabetes care units; the "intensified" group was additionally treated at a cardiac outpatient clinic for the up-titration of renin-angiotensin system (RAS) antagonists and beta-blockers. The primary endpoint was hospitalization/death due to cardiac disease after 2 years.

Results: At baseline, the mean age of the patients was 67.5 ± 9 years, duration of diabetes was 15 ± 12 years, 37% were male, HbA1c was 7 ± 1.1%, blood pressure was 151 ± 22 mm Hg, heart rate was 72 ± 11 beats/min, median NT-proBNP was 265.5 pg/ml (interquartile range: 180.8 to 401.8 pg/ml). After 12 months there was a significant difference between the number of patients treated with a RAS antagonist/beta-blocker and the dosage reached between groups (p < 0.0001). Blood pressure was significantly reduced in both (p < 0.05); heart rate was only reduced in the intensified group (p = 0.004). A significant reduction of the primary endpoint (hazard ratio: 0.351; 95% confidence interval: 0.127 to 0.975, p = 0.044) was visible in the intensified group. The same was true for other endpoints: all-cause hospitalization, unplanned cardiovascular hospitalizations/death (p < 0.05 for all).

Conclusions: Accelerated up-titration of RAS antagonists and beta-blockers to maximum tolerated dosages is an effective and safe intervention for the primary prevention of cardiac events for diabetic patients pre-selected using NT-proBNP. (Nt-proBNP Guided Primary Prevention of CV Events in Diabetic Patients [PONTIAC]; NCT00562952).

Keywords: ACE; N-terminal pro–B-type natriuretic peptide; NT-BNP-selected; NT-proBNP; RAS; RAS antagonists; angiotensin-converting enzyme; beta-blockers; diabetes mellitus; eGFR; estimated glomerular filtration rate; primary prevention; renin-angiotensin system.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Angiotensin Receptor Antagonists / therapeutic use*
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Biomarkers / blood
  • Blood Pressure
  • Diabetes Mellitus, Type 2 / epidemiology*
  • Female
  • Heart Diseases / blood
  • Heart Diseases / epidemiology
  • Heart Diseases / prevention & control*
  • Heart Rate
  • Hospitalization / statistics & numerical data
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Natriuretic Peptide, Brain / blood*
  • Peptide Fragments / blood*
  • Primary Prevention
  • Prospective Studies


  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Biomarkers
  • Peptide Fragments
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain

Associated data

  • ClinicalTrials.gov/NCT00562952