EARLY INCREASE OF VON-WILLEBRAND-FACTOR PREDICTS ADVERSE OUTCOME IN UNSTABLE CORONARY-ARTERY DISEASE - BENEFICIAL-EFFECTS OF ENOXAPARIN

Background-The pathogenesis of unstable angina and non-Q-wave myocardi al infarction is still poorly understood, and early evaluation of prog nosis remains difficult. We therefore studied the predictive value of 5 biological indicators of inflammation, thrombogenesis, vasoconstrict ion, and myocardial necrosis, and we examined the effects of enoxapari n and unfractionated heparin on these markers after 48 hours of treatm ent. Methods and Results-Sixty-eight patients with unstable angina or non-Q-wave myocardial infarction randomized in the international ESSEN CE trial participated in this French substudy. C-reactive protein, fib rinogen; von Willebrand factor antigen, endothelin-1 and troponin I we re measured on admission and 18 hours later. The composite end point o f death, myocardial infarction, recurrent angina, or revascularization was significantly lower at 14 and 30 days of follow-up in patients al located to enoxaparin compared with unfractionated heparin. All acute- phase reactant proteins were elevated on admission and increased furth er at 48 hours, Multivariate analysis demonstrated that the rise of vo n Willebrand factor over 48 hours was a significant and independent pr edictor of the composite end point at both 14 days and 30 days. Moreov er the early increase of von Willebrand factor was more frequent and m ore severe with unfractionated heparin than with enoxaparin (mean chan ge was +8.7+/-8.8% with enoxaparin versus +93.9+/-11.7% with unfractio nated heparin, P<0,0001). The other clinical and biological variables did not predict outcome. Conclusions-In patients with unstable angina or non-Q-wave myocardial infarction, the acute-phase proteins increase over the first 2 days despite medical treatment. The early rise of vo n Willebrand factor is an independent predictor of adverse clinical ou tcome at 14 days and at 30 days. Enoxaparin provides protection as evi denced by the reduced release of von Willebrand factor, which represen ts a favorable prognostic finding.