Anticoagulation after subcutaneous enoxaparin is time sensitive in STEMI patients treated with tenecteplase

Abstract

The adequacy of anticoagulation with enoxaparin as an adjuvant to fibrinolytic therapy for STEMI is unclear and has implications for both efficacy and safety; especially in patients undergoing a pharmacoinvasive reperfusion strategy. A subset of fibrinolytic-treated patients in the WEST study was enrolled in a systematic anti-Xa substudy. All received ASA and subcutaneous (SQ) enoxaparin 1 mg/kg followed by TNK-tPA. Incremental IV dosing of enoxaparin (0.3–0.5 mg/kg) was allowed prior to percutaneous coronary intervention (PCI). Anti-Xa blood samples were drawn prior and after angiography. Data are presented as percentages, medians and IQRs. Forty-five patients underwent angiography 2.8 h (2.5–14.6) after fibrinolytic. The pre-angiography median anti-Xa acquired 179 min (153–875) after SQ enoxaparin was 0.48 U/ml (0.42–0.65); a relationship between anti-Xa activity and time from administration was evident (r = 0.418, p < 0.007). Without supplemental IV enoxaparin the 2nd anti-Xa acquired 218 min (195–930) after SQ enoxaparin was 0.48 U/ml (0.41–0.80, n = 29). After supplemental IV enoxaparin, the 2nd anti-Xa was 0.92 U/ml (0.72–1.10, n = 16). An incremental IV enoxaparin dose and anti-Xa relationship was demonstrated (r = 0.59, p = 0.001) i.e. no IV 0.48 U/ml (0.41–0.80, n = 29), 0.3 mg/kg IV 0.81 U/ml (0.63–1.00, n = 12), and 0.5 mg/kg IV 1.34 U/ml (1.16–1.54, n = 4). Most fibrinolytic treated STEMI patients receiving weight-adjusted SQ enoxaparin (1 mg/kg) had subtherapeutic anti-Xa levels (<0.5 U/ml) after ~3 h. A strategy of supplemental 0.3 mg/kg IV enoxaparin at time of PCI reliably achieved anti-Xa ≥ 0.5 U/ml. Our findings provide a rational novel strategy for anti-thrombotic management in STEMI patients undergoing a pharmacoinvasive reperfusion strategy.