Influence of prolonged dalteparin treatment on coagulation, fibrinolysis and inflammation in unstable coronary artery disease.

Abstract

BACKGROUND:

Unstable coronary artery disease (CAD) is a multi-factorial disease involving thrombotic and inflammatory processes. Short-term low molecular weight (LMW) heparin treatment reduces coagulation activity and clinical events. We investigated the influence of prolonged treatment on coagulation, fibrinolysis and inflammation.

METHODS AND RESULTS:

Serial blood samples were obtained from 555 of 2,267 unstable CAD patients in the FRISC II study. Patients were treated with the LMW heparin dalteparin 120 IU kg(-1) s.c. twice daily for 5-7 days and randomized to placebo (n=285) or gender and weight-adjusted doses of dalteparin (5,000 or 7,500 IU) twice daily (n=270) for 3 months. Dalteparin persistently depressed coagulation activity with, when compared with placebo, lower median levels of factor VIIa (63 IU mL(-1) vs. 84 IU mL(-1)), prothrombin fragment 1 + 2 (0.86 nmol L(-1) vs. 1.09 nmol L(-1)) and D-dimer (21 microg L(-1) vs. 43 microug L(-1)) after 3 months, all P<0.01. Reactivation of coagulation activity was observed after cessation of both short-term and prolonged dalteparin treatment. Higher levels of tPA/PAI-1 complex (11.7 microg L(-1) vs. 6.5 microg L(-1), P<0.001) and von Willebrand factor (162% vs. 136%, P<0.001) were found during prolonged dalteparin treatment. Interleukin-6, C-reactive protein and fibrinogen levels were unaffected by dalteparin treatment.

CONCLUSIONS:

Three months dalteparin treatment resulted in a sustained and pronounced reduction of coagulation activity, which corresponds to the observed reduction in death and myocardial infarction during the initial 6 weeks in the FRISC II study. The persistently elevated levels of tPA/PAI-1 complex and von Willebrand factor might reflect effects on platelets and endothelial cells and thus contribute to the gradually decreased efficacy by prolonged dalteparin treatment in unstable CAD.

• Authors: J Oldgren, C Fellenius, K Boman, J-H Jansson, T K Nilsson, L Wallentin, A Siegbahn
• Journal: Journal of internal medicine (J Intern Med) Vol. 258 Issue 5 Pg. 420-7 (Nov 2005) ISSN: 0954-6820 [Print] England
• PMID: 16238677 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Anticoagulants
• Fibrinolytic Agents
• Interleukin-6
• von Willebrand Factor
• Fibrinogen
• C-Reactive Protein
• Dalteparin

Topics

• Aged
• Anticoagulants (administration & dosage)
• Blood Coagulation (drug effects)
• C-Reactive Protein (analysis)
• Coronary Artery Disease (drug therapy, physiopathology)
• Dalteparin (administration & dosage)
• Double-Blind Method
• Drug Administration Schedule
• Female
• Fibrinogen (analysis)
• Fibrinolysis (drug effects)
• Fibrinolytic Agents (administration & dosage)
• Humans
• Interleukin-6 (blood)
• Male
• Prospective Studies
• Treatment Outcome
• von Willebrand Factor (analysis)