Immediate effects of fluvastain on circulating soluble endothelial protein C and free tissue factor pathway inhibitor in acute coronary syndromes

Background: Statins promptly lower rates of adverse cardiovascular events in patients with acute coronary syndromes (ACS). These therapeutic properties may be mediated by the effects of statins on key hemostatic factors. This study examined the immediate effects of fluvastatin on plasma free tissue factor pathway inhibitor (fTFPI) and soluble endothelial protein C receptor (sEPCR) concentrations in patients with unstable angina or non-ST segment elevation myocardial infarction. Methods: We studied 57 patients consecutively admitted to our emergency department and randomly assigned to placebo (n = 29) versus fluvastatin, 80 mg, p.o. (n = 28). All patients were treated with aspirin and metoprolol p.o., nitroglycerin i.v., and subcutaneous enoxaparin. Venous blood was sampled as soon as possible upon admission, before and 6 h after administration of study drug and standard anti-ischemic therapy. Results: Mean sEPCR concentrations decreased significantly in patients treated with fluvastatin (-8.1 +/- 6.7% from baseline) and was unchanged in the placebo group (-2.3 +/- 14.4%, P = 0.007 vs. fluvastatin). Though fTFPI increased significantly after the administration of both fluvastatin and placebo, the mean increase after fluvastatin (450 +/- 436%) was significantly greater than after placebo (155 +/- 141%, P = 0.001). Conclusions: Treatment with fluvastatin significantly modified key hemostatic factors toward an antithrombotic effect within 6 h. These properties may, in part, explain the early salutary effects of fluvastatin in patients with ACS.