CLINICAL STUDIES: UNSTABLE ANGINA
Effects of various anticoagulant treatments on von Willebrand factor release in unstable angina
Gilles Montalescot, MD, PhD*,
Jean Philippe Collet, MD, PhD*,
Linda Lison, MD*,
R.émi Choussat, MD*,
Annick Ankri, MD ,
Eric Vicaut, MD, PhD ,
Katy Perlemuter, MD*,
François Philippe, MD*,
G.érard Drobinski, MD, PhD* and
Daniel Thomas, MD*
* Department of Cardiology, Pitié-Salpétrière Hospital, Paris, France
Laboratory of Hemostasis, Pitié-Salpétrière Hospital, Paris, France
Laboratory of Biophysics, F. Widal Hospital, Paris, France
Manuscript received September 8, 1999;
revised manuscript received January 17, 2000,
accepted March 6, 2000.
Reprint requests and correspondence: Gilles Montalescot, Department of Cardiology, Centre Hospitalier Universitaire Pitié-Salpétrière, 47 boulevard de l’Hôpital, 75013, Paris, France.
gilles.montalescot{at}psl.ap-hop-paris.fr
OBJECTIVES
We tested the hypothesis that different anticoagulant treatments may produce different platelet effects and von Willebrand factor (vWf) release in unstable angina.
BACKGROUND
The early increase of vWf has been reported to be a risk factor for adverse outcome in unstable angina. Anticoagulant drugs play a key role in stabilization of unstable angina, but they may not have the same efficacy and the same effects on acute vWf release.
METHODS
We studied 154 patients enrolled in several clinical trials testing four different anticoagulant treatments in unstable angina or non-Q-wave myocardial infarction. Patients were treated during at least 48 h by either intravenous unfractionated heparin, one of two different low molecular weight heparins (enoxaparin or dalteparin) or the direct thrombin inhibitor PEG-hirudin. All patients received aspirin but no IIb/IIIa inhibitors.
RESULTS
The release of vWf over the first 48 h ( vWf) did not relate to the baseline clinical characteristics. At 30 days of follow-up, vWf was sevenfold higher in patients with an end point (death, myocardial infarction, revascularization) than in patients free of events (+53 ± 7% vs. +7 ± 14%, p = 0.004). The same trend was present for each component of the composite end point with the highest levels for one-month mortality (+87 ± 32% vs. +26 ± 8%, p = 0.09). The vWf values did not increase over 48 h in patients receiving either enoxaparin or PEG-hirudin (+10 ± 9% and –5 ± 20%, respectively). A serious rise of vWf was measured in unfractionated heparin-treated patients (+87 ± 11%), which differed significantly from the enoxaparin group (p = 0.0006) and PEG-hirudin group (p < 0.0001). In dalteparin-treated patients, vWf was elevated (+48 ± 8%) and did not differ from the unfractionated heparin group (NS).
CONCLUSIONS
We confirm that, in unstable angina patients, a rise of vWf over the first 48 h is associated with an impaired outcome at 30 days. Moreover, the four different anticoagulant treatments tested here do not provide the same protection with regards to vWf release, which may have important prognostic implications and explain different results observed in recent clinical trials.
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Abbreviations and Acronyms
| | aPTT | = activated partial thromboplastin time | | CABG | = coronary artery bypass graft | | CK | = creatine kinase | | ECG | = electrocardiogram | | PTCA | = percutaneous transluminal coronary angioplasty | | vWf | = von Willebrand factor |
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