Use of a standardized heparin nomogram to achieve therapeutic anticoagulation after thrombolytic therapy in myocardial infarction. TIMI 4 investigators. Thrombolysis in Myocardial Infarction.

BACKGROUND The recently completed Thrombolysis in Myocardial Infarction (TIMI) 4 Study compared three thrombolytic treatment regimens for acute myocardial infarction. The treatment arms included front-loaded recombinant tissue plasminogen activator (rtPA), anistreplase (APSAC), or both, in conjunction with an intravenous bolus of 5000 U of heparin, followed by 1000 U/h. To facilitate anticoagulation, a heparin nomogram was developed to maintain the therapeutic activated partial thromboplastin time at 1 1/2 to 2 times the control value. METHODS A poll revealed that nine centers made use of the recommended heparin nomogram and six did not, adjusting the heparin dosage according to local practice. Anticoagulation parameters, major hemorrhagic events, and the frequency of heparin interruption were compared between centers that used and did not use the nomogram. RESULTS Subtherapeutic activated partial thromboplastin time values were noted in 4%, 14%, 29%, 46%, 37%, and 34% of patients 8, 12, 24, 48, 72, and 96 hours, respectively, after heparin treatment was begun. Patients with subtherapeutic values at 24 hours were younger (mean +/- SD, 55.2 +/- 10.6 vs 59.6 +/- 10.6 years, P = .02) and weighed more (86.4 +/- 13.5 vs 78.9 +/- 15.7 kg, P = .007) than patients with therapeutic values. Centers that used the nomogram had significantly fewer subtherapeutic values at 48 and 96 hours. In addition, heparin therapy was interrupted less frequently at centers that used the nomogram (38.1% vs 68.7%, P < .001). Major spontaneous hemorrhage, reinfarction, and reocclusion rates were low and were about the same in the two groups. CONCLUSIONS The use of a heparin nomogram provided improved anticoagulation in patients treated with thrombolytic therapy for myocardial infarction. Weight- and age-adjusted heparin dosing may provide further improvement in anticoagulation with heparin therapy. Our findings support the need for frequent monitoring of the activated partial thromboplastin time and for a standardized approach to adjusting the heparin dosage.

[1]  Craig D. Miller,et al.  Management of Patients With Intramural Hematoma of the Thoracic Aorta , 1993, Circulation.

[2]  M. Simoons,et al.  Correlation between level of heparinization and patency of the infarct-related coronary artery after treatment of acute myocardial infarction with alteplase (rt-PA). , 1992, Journal of the American College of Cardiology.

[3]  G. Raskob,et al.  Optimal therapeutic level of heparin therapy in patients with venous thrombosis. , 1992, Archives of internal medicine.

[4]  J. Hsia,et al.  Heparin-induced prolongation of partial thromboplastin time after thrombolysis: relation to coronary artery patency. HART Investigators. , 1992, Journal of the American College of Cardiology.

[5]  M. Pfisterer,et al.  Effect of early intravenous heparin on coronary patency, infarct size, and bleeding complications after alteplase thrombolysis: results of a randomised double blind European Cooperative Study Group trial. , 1992, British heart journal.

[6]  H. Hellstrom.  Consequences of reocclusion after successful reperfusion therapy in acute myocardial infarction. , 1991, Circulation.

[7]  J. Hirsh,et al.  A standard heparin nomogram for the management of heparin therapy. , 1991, Archives of internal medicine.

[8]  J. Hirsh.  Drug therapy : heparin , 1991 .

[9]  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.

[10]  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.

[11]  R. Califf,et al.  Consequences of reocclusion after successful reperfusion therapy in acute myocardial infarction. TAMI Study Group. , 1990, Circulation.

[12]  H. S. Mueller,et al.  The Thrombolysis in Myocardial Infarction (TIMI) trial. Phase I findings. , 1985, The New England journal of medicine.