Effects of various anticoagulant treatments on von Willebrand factor release in unstable angina

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 (Δ vWf) did not relate to the baseline clinical characteristics. At 30 days of follow-up, Δ 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, Δ 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.