More predictable anticoagulation with intravenous enoxaparin than with unfractionated heparin in patients undergoing primary percutaneous coronary intervention: a substudy of the ATOLL trial

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) randomised trial showed that intravenous enoxaparin compared with unfractionated heparin (UFH) significantly reduced ischemic events with non significant reductions in bleeding complications. Purpose: To compare the efficacy of enoxaparin and UFH in achieving target anticoagulation levels during percutaneous coronary intervention, and to correlate this with ischaemic and bleeding events at 1 month follow up. Methods: This was a single centre biological sub-study. 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). To demonstrate pharmacological efficacy we chose target ranges of 0.5-1.2 IU/ml for anti Xa levels for enoxaparin and 1.5-2.5 IU/ml activated partial thromboplastin time (APTT) ratio for UFH treated patients. Results: A total of 133 patients (n=58 enoxaparin and n=71 UFH) were included. Baseline characteristics were matched apart from greater use of glycoprotein IIb/IIIa inhbitors in the UFH group (p=0.04). Of these 51 patients (n=20 enoxaparin, n=31 UFH, p= 0.288) were randomized pre-hospital in the mobile intensive care unit (MICU). In the pre-hospital treatment group more patients treated with enoxaparin were on-target than UFH at both T1 (78.9 vs 15.4%), p<0.0001) and T2 (84.2 vs 32.1%, p=0.0008). These findings were consistent in the overall group regardless of upstream treatment with target anticoagulation levels at T2 more readily achieved in patients receiving enoxaparin (80% vs 18.2%, p<0.0001). The incidence of major bleeding did not differ between groups, however minor bleeding occurred less commonly in enoxaparin treated patients (OR 0.54, 95% CI 0.28 to 0.98, p=0.03). However, anti Xa and APTT ratio levels did not correlate with major or minor bleeding (p=0.83, 0.72). Likewise there was no correlation between anticoagulation levels and ischemic events but mean levels of APTT were significantly lower in patients with procedure failure (150±19.1s vs 204.6±16.0s, p=0.03). Conclusions: In STEMI patients undergoing primary PCI target anticoagulation levels were more readily achieved in patients receiving intravenous enoxaparin than UFH. The more predictable and stable anticoagulation obtained with enoxaparin may explain the better outcomes observed in the main study.