Abstract
Background: The ATOLL (Acute ST-elevation myocardial infarction Treated with primary angioplasty and intravenous enoxaparin Or unfractionated heparin to Lower ischemic and bleeding events at short- and Long-term follow-up) randomized trial showed that intravenous heparin compared with unfractionated heparin (UFH) significantly reduced ischemic events. Purpose: The study aimed to assess biomarkers of coagulation and platelet activation in patients on intravenous enoxaparin or UFH in the primary PCI (PPCI) setting with significant antiplatelet therapy and to correlate these findings with 1 month clinical outcomes. Methods: Patients presenting with STEMI that were randomized to receive an intravenous bolus or either enoxaparin or UFH had blood sampling performed at sheath insertion at the commencement (T1) and at the end of the PPCI procedure (T2). The thrombotic factors, von Willebrand factor antigen (vWFAg), prothrombin fragment 1+2 (F1+2), thrombin-antithrombin (TAT) complex, tissue factor pathway inhibitor (TFPI) were measured along with the platelet marker, soluble CD40 ligand (sCD40L). Results were correlated with the primary endpoint, a composite of death, complication of MI, procedure failure, or major bleeding (net clinical benefit) and the main secondary outcome, a composite of death, recurrent ACS, or urgent revascularization (ischemic outcome) Results: A total of 129 patients (n=58 enoxaparin and n=71 UFH) were included. Baseline characteristics and treatment were matched apart from a greater use of glycoprotein IIb/IIa inhbitors in the UFH group (p=0.04). Of the numerous parameters measured, univariate analysis identified significant association between increased plasma levels of F1+2 and TAT measured at T2 and the incidence of both the primary endpoint (p=0.05 and p=0.03) and the secondary ischemic endpoint (p=0.035 and 0.036). The increasing release of F1+2 between T1 and T2 (Δ T2-T1) also predicted the primary (184.9±61.1 vs 3.2±34.7 pmol/L, p= 0.01) and secondary endpoints (318.8±132.2 vs 36.9±30.3 pmol/L, p=0.05). Multivariate analysis identified increased plasma levels of F1+2 and TAT complex as independent correlates of the secondary ischemic endpoint at 1 month. Although patients treated with enoxaparin compared with UFH showed a trend to decreased release (Δ T2-T1) of both F1+2 and TAT (23.6±49.7 vs 119±44.6 pmol/L and 4.0±4.1 vs 9.1±3.2 respectively), the impact did not reach statistical significance (p=0.15 and 0.33, respectively) Conclusions: In this substudy of the ATOLL trial, markers of thrombin generation F1+2 and TAT complex are independently associated with short-term adverse ischemic events in PPCI patients.
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