One-year results from the landmark ExTRACT-TIMI (Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment, Thrombolysis in Myocardial Infarction) 25 and STEEPLE (SafeTy and Efficacy of Enoxaparin in Percutaneous Coronary Intervention Patients) studies have confirmed a clear net clinical benefit for patients with acute ST-segment elevation myocardial infarction (STEMI) for Lovenox (enoxaparin) vs Unfractionnated Heparin (UFH). The outcomes were presented at the European Society of Cardiology, in Vienna, Austria.
Lovenox (enoxaparin sodium injection - sanofi-aventis) is a unique chemical entity in a class of antithrombotic agents known as lowmolecular weight heparin (LMWH) and is obtained by alkaline degradation of heparin benzyl ester and is about one-third the molecular size of unfractionated heparin.
ExTRACT TIMI 25
ExTRACT TIMI 25 was a major randomised clinical trial that supported the worldwide submission and subsequent approval by the FDA and some European countries of the new Lovenox indication for the treatment of patients with acute STEMI. The trial showed that in patients with STEMI treated with fibrinolysis, at one year, the primary endpoint of death or nonfatal myocardial infarction remained significantly in favour or enoxaparin vs. UFH (15.8% vs. 17.0% p=0.01). Net clinical benefit (all cause of death/nonfatal MI/nonfatal disabling stroke) was also significantly in favour of enoxaparin vs. UFH through one year of follow-up (16.0% vs. 17.3% p=0.007).
As previously reported (Antman EM, Morrow DA, McCabe CH, et al; ExTRACTTIMI 25 Investigators. Enoxaparin versus unfractionated heparin with fibrinolysis for STelevation myocardial infarction. N Engl J Med. 2006;354:1477-1488), the 30-day outcomes showed that in patients with STEMI treated with fibrinolysis, enoxaparin significantly reduced the rate of death or recurrent by 17% vs. unfractionated heparin (UFH) (9.9% vs. 12.0% p<0.001). The benefit of enoxaparin, as compared to UFH, was observed both in patients who underwent percutaneous coronary intervention within 30 days after randomisation or who were treated medically. The rates of major bleeding (including intracranial haemorrhage) at 30 days were 2.1% in the enoxaparin group and 1.4% in the UFH group (p<0.001). The 30 day rate of the composite endpoint of death, myocardial nonfatal reinfarction or nonfatal intracranial haemorrhage (a measure of net clinical benefit) was significantly lower in the enoxaparin group as compared to the unfractionated heparin group (10.1% vs. 12.2%, p<0.001).
"This was a very large trial with conclusive results at 30 days. The persistence of significant net clinical benefit a full year after treatment is further evidence of the viability of the strategy of using enoxaparin as adjunctive anticoagulant therapy to fibrinolysis in the STEMI patient population," commented Dr Elliott Antman, Principal Investigator of ExTRACT TIMI 25 Director, Samuel A Levine Cardiac Unit at Brigham and Women's Hospital, Professor of Medicine, Harvard Medical School.
STEEPLE
STEEPLE randomised 3,528 patients from 124 sites to one of two doses of Lovenox (0.5mg/kg or 0.75mg/kg) or UFH adjusted for activated clotting time, with GP IIb/IIIa inhibition used at the discretion of the operator. The primary endpoint of the study was non-CABG major and minor bleeding out to 48 hours. Secondary endpoints included percentage of patients in whom target anticoagulation levels were reached, various combinations of non-CABG major or minor bleeding, death, nonfatal MI, and/or urgent target vessel revascularisation (UTVR) at 30 days (Montalescot G, White HD, Gallo R, et al; STEEPLE Investigators. Enoxaparin versus unfractionated heparin in elective percutaneous coronary intervention. N Engl J Med. 2006;355:1006-1017). STEEPLE trial one year follow-up shows that the composite of all cause death at one-year and major bleeding was 3.1% for Lovenox 0.5mg/kg (p=0.06 vs. UFH), 3.4% for Lovenox 0.75mg/kg (p=0.07 vs. UFH), 3.3% for the two Lovenox arms combined (p=0.03 vs. UFH) and 4.7% for UFH.
There were low and statistically similar oneyear death rates in the Lovenox groups (0.5mg/kg or 0.75mg/kg) and UFH during and after elective percutaneous intervention (PCI). In addition to patient risk factors, ischaemic events and major bleeding were found to be independent predictors of death at one-year. Dr Gilles Montalescot, Professor of Cardiology, Institute of Cardiology, Hopital de la Pitie Salpetriere, Institut du Coeur, Paris, France, and a member of the STEEPLE steering committee, commented, "The significant reduction in major bleeding and similar efficacy compared with UFH confirms Lovenox is an appropriate anticoagulant for elective PCI."
Lovenox is approved in the US for the prophylaxis of ischaemic complications of unstable angina and non-Q-wave (non-ST-segment elevation) myocardial infarction when concurrently administered with aspirin and for the prophylaxis of deep vein thrombosis (DVT) which may lead to pulmonary embolism (PE); in patients undergoing abdominal surgery who are at risk for thromboembolic complications; in patients undergoing hip replacement surgery (during and following hospitalisation), in patients undergoing knee replacement surgery; and in medical patients who are at risk for thromboembolic complications due to severely restricted mobility during acute illness; as well as for the inpatient treatment of acute DVT, with or without PE, when administered in conjunction with warfarin sodium and for the outpatient treatment of acute DVT without PE, when administered in conjunction with warfarin sodium.
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