Enoxaparin and fibrinolysis: ExTRACTing prognosis from bleeding complications

This editorial refers to ‘One-year outcomes after a strategy using enoxaparin vs. unfractionated heparin in patients undergoing fibrinolysis for ST-segment elevation myocardial infarction: 1-year results of the ExTRACT-TIMI 25 trial’[†][1], by D.A. Morrow et al. , on page 2097 and ‘Relations between bleeding and outcomes in patients with ST-elevation myocardial infarction in the ExTRACT-TIMI 25 trial’[‡][2], by R.P. Giugliano et al. , on page 2103 Pharmacological reperfusion of an occluded coronary artery using a fibrinolytic agent is still the only treatment option for many patients presenting with acute ST-elevation myocardial infarction (STEMI) in many centres worldwide. To reduce the risk of early reocclusion, anticoagulants need to be given as an adjunct to lytic therapy. In this setting, low molecular weight heparins (LMWHs) offer several advantages over standard unfractionated heparin (UFH): greater bioavailability, better resistance to inhibition by activated platelets, lower incidence of heparin-induced thrombocytopenia, and a higher anti-Xa:IIa ratio and therefore more efficient inhibition of thrombin generation. Furthermore, LMWHs do not need monitoring, have a longer half-life, and can be given subcutaneously, which facilitates daily administration. LMWHs have been tested extensively as an adjunct to fibrinolysis in STEMI patients. In patency studies, they were found to be associated with higher early patency rates and lower rates of reocclusion.1–4 In ASSENT-3, a significant improvement in the primary combined efficacy and safety endpoint was seen with enoxaparin compared with UFH in patients treated with tenecteplase.5,6 Unfortunately, a significant increase in intracranial haemorrhages (ICHs) was observed in its companion pre-hospital trial, ASSENT-3 PLUS, using the same treatment combination.7 The excess of ICHs was observed exclusively in patients above 75 years of age; major non-ICH bleeding complications were also much higher with enoxaparin (7.2%) than with UFH (4.0%) in the elderly. Using an age-adjusted dose (no bolus and 75% … *Corresponding author. Tel: +32 16 344235, Fax: +32 16 344240, Email: peter.sinnaeve{at}uzleuven.be [1]: #fn-2 [2]: #fn-3