N-terminal pro-B-type natriuretic peptide concentrations predict the risk of cardiovascular adverse events from antiinflammatory drugs: a pilot trial

Clin Chem. 2008 Jul;54(7):1149-57. doi: 10.1373/clinchem.2007.097428. Epub 2008 May 1.

Abstract

Background: we investigated whether higher concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) predicts cardiovascular adverse events (CV-AEs) in patients with osteoarthritis treated with antiinflammatory drugs.

Methods: NT-proBNP was measured in baseline samples from 433 patients enrolled in a prospective randomized study designed to test the therapeutic effect of a novel metalloproteinase inhibitor. We monitored CV-AEs and retrospectively investigated their relationship to the concomitant use of selective cyclooxygenase-2 inhibitors (coxibs), traditional nonsteroidal antiinflammatory drugs (tNSAIDs), and glucocorticoids. CV-AEs included myocardial infarction, stroke, new or worsening of preexisting arterial hypertension, congestive heart failure, and several less severe CV-AEs.

Results: we observed 82 mild to serious CV-AEs during an observational period of 200 days. The risk of such events was 1.95-fold higher in patients who were taking tNSAIDs, glucocorticoids, or coxibs (i.e., any inhibitor) and who had NT-proBNP concentrations > or = 100 ng/L than in patients taking any inhibitor who had NT-proBNP values <100 ng/L (P < 0.05). Patients taking coxibs (alone or in addition to tNSAIDs or glucocorticoids) with baseline NT-proBNP values > or = 100 ng/L had a 7.41-fold higher risk for CV-AEs than those with baseline values <100 ng/L (P < 0.01). Patients who were taking 2 or more antiinflammatory drugs and had NT-proBNP values > or = 100 ng/L had a 3.74-fold higher risk for CV-AEs than those with NT-proBNP values <100 ng/L (P < 0.05). An NT-proBNP value <100 ng/L was associated with negative predictive values of >85% across all treatment groups.

Conclusions: NT-proBNP may be a useful marker for anticipating cardiovascular risk associated with the use of antiinflammatory drugs for osteoarthritis.

Publication types

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

MeSH terms

  • Anti-Inflammatory Agents / adverse effects*
  • Anti-Inflammatory Agents / therapeutic use
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Biomarkers / blood
  • Cardiovascular Diseases / chemically induced*
  • Cardiovascular Diseases / epidemiology
  • Double-Blind Method
  • Female
  • Glucocorticoids / adverse effects
  • Humans
  • Male
  • Metalloproteases / antagonists & inhibitors
  • Middle Aged
  • Natriuretic Peptide, Brain / blood*
  • Osteoarthritis / drug therapy
  • Peptide Fragments / blood*
  • Pilot Projects
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Assessment

Substances

  • Anti-Inflammatory Agents
  • Anti-Inflammatory Agents, Non-Steroidal
  • Biomarkers
  • Glucocorticoids
  • Peptide Fragments
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • Metalloproteases