Myocardial damage, inflammation and thrombin inhibition in unstable coronary artery disease

Eur Heart J. 2003 Jan;24(1):86-93. doi: 10.1016/s0195-668x(02)00312-3.


Aim: Unstable coronary artery disease (CAD) is a multifactorial disease involving both thrombotic and inflammatory processes. We have assessed the time-course and the influence of thrombin inhibitors on changes in fibrinogen and C-reactive protein levels, and their relation to myocardial ischaemia in unstable CAD.

Methods and results: Three hundred and twenty patients were randomized to 72 h infusion with three different doses of inogatran, a direct thrombin inhibitor, or unfractionated heparin. There were no significant differences between the treatment groups in fibrinogen or C-reactive protein levels. Overall, the fibrinogen levels were significantly increased in the first 24-96 h and still elevated at 30 days. The C-reactive protein levels showed a more pronounced increase during the first 24-96 h, but then markedly decreased over 30 days. Troponin-positive compared to troponin-negative patients had higher fibrinogen and C-reactive protein levels up to 96 h, although there was an increase compared to pre-treatment levels in both groups. A high fibrinogen level (pre-treatment top tertile) was associated with an increased rate of death or myocardial (re-)infarction at 30 days, 13% vs 5.6%, P=0.03, and increased long-term mortality. A high C-reactive protein level was related to increased 30-day mortality, 4% vs 0%, P=0.01.

Conclusion: Myocardial cell injury was related to a high degree of inflammation, only some of which is an acutephase response due to tissue damage. The rise in fibrinogen was sustained, which might reflect low grade inflammation with long-term risk of thrombosis. The transient elevation of C-reactive protein levels might indicate a propensity to a pronounced inflammatory response and is associated with increased mortality.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antithrombins / administration & dosage*
  • C-Reactive Protein / metabolism
  • Coronary Disease / blood*
  • Coronary Disease / drug therapy
  • Female
  • Fibrinogen / metabolism
  • Follow-Up Studies
  • Glycine / administration & dosage*
  • Glycine / analogs & derivatives*
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / blood
  • Myocarditis / etiology*
  • Myocarditis / metabolism
  • Piperidines / administration & dosage*
  • Survival Analysis
  • Troponin T / blood


  • Antithrombins
  • Piperidines
  • Troponin T
  • inogatran
  • Fibrinogen
  • C-Reactive Protein
  • Glycine