Replacing Standard Heparin with Enoxaparin in MIs
From the 2001 Scientific Sessions of the American Heart Association (November 13, 2001; Anaheim, CA), the compelling results of the thrombolysis in myocardial infarction study--ENTIRE-TIMI 23 (enoxaparin and TNK-tPA with or without GP IIb/IIIa inhibitor as reperfusion strategy in ST elevation MI) were revealed by Elliott M. Antman, MD, principal investigator, and other researchers from the Brigham and Women's Hospital, Boston, MA).

Antman said that earlier trials demonstrated the superiority of enoxaparin in the acute management of unstable angina and non-Q-wave heart attack, and now these studies suggest enoxaparin to be an appropriate antithrombotic adjunctive agent for ST-elevation acute coronary syndromes. In this report, the researchers advanced that enoxaparin, a subcutaneous, low-molecular-weight heparin, when added to tenecteplase (TNK, a clot-buster), with or without abciximab, is a safe and effective replacement for standard unfractionated heparin (UFH). In fact, they reported lower rates of death or recurrent heart attack at 30 days in the enoxaparin group.

Enoxaparin is the most widely studied and used low-molecular-weight heparin in the world. Fourteen years of experience, including the treatment of 82 million patients in 96 countries, have proven enoxaparin to be safe and effective in the prevention and treatment of venous and arterial thrombosis.

Experimental Design: In the Phase II, 483-patient ENTIRE trial patients were randomized to receive either standard reperfusion therapy with a full-dose of the thrombolytic tenecteplase or combination therapy with half-dose tenecteplase and the glycoprotein IIb/IIIa receptor antagonist abciximab. Patients also received either UFH or one of several different regimens of enoxaparin. The primary efficacy endpoint was TIMI 3 coronary flow (normal blood flow) at 60 minutes, and the primary safety endpoint was TIMI major hemorrhage (overt bleeding resulting in a loss of 5 pints of blood) at 30 days.

Results: TIMI 3 flow rates with enoxaparin were similar to UFH at 60 minutes, regardless of the pharmacologic regimen (51% vs. 49%). Over time, however, patients treated with enoxaparin showed a trend towards higher rates of ST-segment resolution at 180 minutes (51% vs. 45%), a secondary endpoint of the trial. The rate of death or recurrent heart attack through 30 days was significantly lower with enoxaparin (5.0%) compared with UFH (10.7%) (p=0.02). Patients receiving enoxaparin had similar overall rates of TIMI major hemorrhage at 30 days compared with patients receiving UFH (2.5% vs. 2.4%) when full-dose TNK was prescribed.

• The HART II (heparins and aspirin reperfusion therapy) study demonstrated that patients who received enoxaparin in conjunction with rt-PA, or alteplase, achieved equivalent artery patency at 90 minutes compared to patients receiving rt-PA and UFH.
• The AMI-SK (Acute Myocardial Infarction - StreptoKinase) trial found that combining enoxaparin and streptokinase significantly improved restoration of normal coronary blood flow and outcome in AMI patients.
• In the larger, ASSENT 3 (assessment of the safety and efficacy of new thrombolytic regimens) study, heart attack patients who received enoxaparin with full-dose tenecteplase experienced fewer ischemic complications of AMI than those treated with UFH and full-dose tenecteplase. These reductions were similar to but more consistent than those seen in the group receiving half-dose tenecteplase plus abciximab and UFH.