Randomized Comparison of Enoxaparin, a Low-Molecular-Weight Heparin, With Unfractionated Heparin Adjunctive to Recombinant Tissue Plasminogen Activator Thrombolysis and Aspirin Second Trial of Heparin and Aspirin Reperfusion Therapy (HART II)

Background— Adjunctive unfractionated heparin (UFH) during thrombolytic therapy for acute myocardial infarction (AMI) promotes the speed and magnitude of coronary artery recanalization and reduces reocclusion. Low-molecular-weight heparins offer practical and potential pharmacological advantages over UFH in multiple applications but have not been systematically studied as adjuncts to fibrinolysis in AMI. Methods and Results— Four hundred patients undergoing reperfusion therapy with an accelerated recombinant tissue plasminogen activator regimen and aspirin for AMI were randomly assigned to receive adjunctive therapy for at least 3 days with either enoxaparin or UFH. The study was designed to show noninferiority of enoxaparin versus UFH with regard to infarct-related artery patency. Ninety minutes after starting therapy, patency rates (thrombolysis in myocardial infarction [TIMI] flow grade 2 or 3) were 80.1% and 75.1% in the enoxaparin and UFH groups, respectively. Reocclusion at 5 to 7 days from TIMI gra...

[1]  K. Coyne,et al.  Low—molecular—weight heparins in acute myocardial infarction: RationaLe and results of a pilot study , 2000, Clinical cardiology.

[2]  E. Antman,et al.  Enoxaparin prevents death and cardiac ischemic events in unstable angina/non-Q-wave myocardial infarction. Results of the thrombolysis in myocardial infarction (TIMI) 11B trial. , 1999, Circulation.

[3]  A. Siegbahn,et al.  Low molecular weight heparin (dalteparin) as adjuvant treatment of thrombolysis in acute myocardial infarction--a pilot study: biochemical markers in acute coronary syndromes (BIOMACS II). , 1999, Journal of the American College of Cardiology.

[4]  R. Califf,et al.  1999 update: ACC/AHA guidelines for the management of patients with acute myocardial infarction. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Acute Myocardial Infarction). , 1996, Journal of the American College of Cardiology.

[5]  M. Keltai,et al.  Comparison of two treatment durations (6 days and 14 days) of a low molecular weight heparin with a 6-day treatment of unfractionated heparin in the initial management of unstable angina or non-Q wave myocardial infarction: FRAX.I.S. (FRAxiparine in Ischaemic Syndrome). , 1999, European heart journal.

[6]  J. Hirsh.  Low-molecular-weight heparin for the treatment of venous thromboembolism. , 1998, American heart journal.

[7]  R. Califf,et al.  Economic assessment of low-molecular-weight heparin (enoxaparin) versus unfractionated heparin in acute coronary syndrome patients: results from the ESSENCE randomized trial. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q wave Coronary Events [unstable angina or non-Q-wave myocardial infarc , 1998, Circulation.

[8]  R. Califf,et al.  Thrombin generation, inhibition and clinical outcomes in patients with acute myocardial infarction treated with thrombolytic therapy and heparin: results from the GUSTO-I Trial. GUSTO-I Hemostasis Substudy Group. Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries. , 1998, Journal of the American College of Cardiology.

[9]  T. Pedersen,et al.  Randomized trial of low molecular weight heparin (dalteparin) in prevention of left ventricular thrombus formation and arterial embolism after acute anterior myocardial infarction: the Fragmin in Acute Myocardial Infarction (FRAMI) Study. , 1997, Journal of the American College of Cardiology.

[10]  R. Califf,et al.  A comparison of low-molecular-weight heparin with unfractionated heparin for unstable coronary artery disease. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events Study Group. , 1997 .

[11]  W. Klein,et al.  Comparison of low-molecular-weight heparin with unfractionated heparin acutely and with placebo for 6 weeks in the management of unstable coronary artery disease. Fragmin in unstable coronary artery disease study (FRIC) , 1997, Circulation.

[12]  E. Antman.  Hirudin in acute myocardial infarction. Thrombolysis and Thrombin Inhibition in Myocardial Infarction (TIMI) 9B trial. , 1996, Circulation.

[13]  B. Boneu.  New antithrombotic agents for the prevention and treatment of deep vein thrombosis. , 1996, Haemostasis.

[14]  E. Gurfinkel,et al.  Low molecular weight heparin versus regular heparin or aspirin in the treatment of unstable angina and silent ischemia. , 1995, Journal of the American College of Cardiology.

[15]  J. Fareed,et al.  New Anticoagulants for the Cardiovascular Patient , 1995 .

[16]  U. Tebbe,et al.  Impact of early perfusion status of the infarct-related artery on short-term mortality after thrombolysis for acute myocardial infarction: retrospective analysis of four German multicenter studies. , 1993, Journal of the American College of Cardiology.

[17]  R. Seitz,et al.  Prothrombin activation by thrombolytic agents , 1993 .

[18]  D. Tate,et al.  Effect of heparin on coronary arterial patency after thrombolysis with tissue plasminogen activator in acute myocardial infarction. , 1990, The American journal of cardiology.

[19]  J. Hsia,et al.  A comparison between heparin and low-dose aspirin as adjunctive therapy with tissue plasminogen activator for acute myocardial infarction. Heparin-Aspirin Reperfusion Trial (HART) Investigators. , 1990, The New England journal of medicine.

[20]  Sarah Parish,et al.  Randomized trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2.ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. , 1988, Journal of the American College of Cardiology.

[21]  Y. Ohtsuki,et al.  ISOLATION OF HTLV-I FROM CEREBROSPINAL FLUID OF A PATIENT WITH MYELOPATHY , 1986, The Lancet.

[22]  Gruppo Italiano per lo Studio della Soprawivenza nell'Inf Miocardico.,et al.  EFFECTIVENESS OF INTRAVENOUS THROMBOLYTIC TREATMENT IN ACUTE MYOCARDIAL INFARCTION , 1986, The Lancet.

[23]  R. W. Brower,et al.  DOUBLE-BLIND RANDOMISED TRIAL OF INTRAVENOUS TISSUE-TYPE PLASMINOGEN ACTIVATOR VERSUS PLACEBO IN ACUTE MYOCARDIAL INFARCTION , 1985, The Lancet.

[24]  R. Collins,et al.  Intravenous and intracoronary fibrinolytic therapy in acute myocardial infarction: overview of results on mortality, reinfarction and side-effects from 33 randomized controlled trials. , 1985, European heart journal.