Correlation between level of heparinization and patency of the infarct-related coronary artery after treatment of acute myocardial infarction with alteplase (rt-PA)

Center for Thrombosis and Vascular Research, University of Leuven, Belgium.

BACKGROUND AND OBJECTIVES. The conjunctive use of intravenous heparin may influence the efficacy of alteplase for coronary thrombolysis in patients with acute myocardial infarction. In this study we examined the relation between the level of intravenous anticoagulation with heparin and sustained coronary artery patency in a subgroup of patients of the European Cooperative Study Group (ECSG) trial. METHODS. In the ECSG trial, patients treated with alteplase and aspirin were randomized to concomitant fixed doses of intravenous heparin (a bolus dose of 5,000 U followed by a continuous infusion of 1,000 U/h or placebo). The current study group comprised 149 of 324 ECSG patients allocated to heparin therapy and 132 of 320 ECSG patients allocated to placebo administration who had both an interpretable coronary angiogram obtained within 6 days of treatment and sufficient plasma samples to assess the level of anticoagulation. Activated partial thromboplastin times, fibrinogen and D-dimer levels were determined on plasma samples at baseline and at 45 min and 3, 12, 24 and 36 h after the start of alteplase administration. RESULTS. The coronary artery patency rate was higher in patients allocated to heparin therapy than in those allocated to placebo (80% and 71%, respectively, p = 0.05). Patients allocated to heparin were classified into three subgroups: 48 patients (32%) with all activated partial thromboplastin times at least twice their own baseline value (optimal anticoagulation), 40 patients (27%) with the lowest activated partial thromboplastin time at 3, 12, 24 or 36 h between 130% and 200% of the baseline value (suboptimal anticoagulation) and 61 patients with at least one activated partial thromboplastin time less than 130% of baseline (inadequate anticoagulation). In the heparin group, coronary artery patency correlated with the level of anticoagulation: 90%, 80% and 72%, respectively, in patients with optimal, suboptimal and inadequate anticoagulation (p = 0.02, optimal vs. inadequate anticoagulation). Heparin administration was associated with a smaller reduction in fibrinogen and a smaller increase in D-dimer level during and after alteplase administration. No correlation was found between fibrinogen or D-dimer levels and coronary artery patency. No intracerebral hemorrhage occurred in these patients; however, bleeding was more frequent in the subgroup with optimal anticoagulation (p = 0.05). CONCLUSIONS. Intense anticoagulation with intravenous heparin enhances coronary artery patency after alteplase treatment of acute myocardial infarction.

This article has been cited by other articles:

				J. Hirsh, S. S. Anand, J. L. Halperin, and V. Fuster Guide to Anticoagulant Therapy: Heparin : A Statement for Healthcare Professionals From the American Heart Association Arterioscler. Thromb. Vasc. Biol., July 1, 2001; 21 (7): e9 - e9. [Full Text] [PDF]

				J. Hirsh, S. S. Anand, J. L. Halperin, and V. Fuster Guide to Anticoagulant Therapy: Heparin : A Statement for Healthcare Professionals From the American Heart Association Circulation, June 19, 2001; 103(24): 2994 - 3018. [Full Text] [PDF]

				J. Hirsh, T. E. Warkentin, S. G. Shaughnessy, S. S. Anand, J. L. Halperin, R. Raschke, C. Granger, E. M. Ohman, and J. E. Dalen Heparin and Low-Molecular-Weight Heparin Mechanisms of Action, Pharmacokinetics, Dosing, Monitoring, Efficacy, and Safety Chest, January 1, 2001; 119(1_suppl): 64S - 94S. [Full Text] [PDF]

				S A J Chamuleau, R J de Winter, M Levi, R Adams, H R Büller, M H Prins, K I Lie, and R J G Peters Low molecular weight heparin as an adjunct to thrombolysis for acute myocardial infarction: the FATIMA study Heart, July 1, 1998; 80(1): 35 - 39. [Abstract] [Full Text]

				M. Levi, R. J.G. Peters, and H. R. Buller Weight watching in cardiology: low molecular weight heparin for acute coronary syndromes Cardiovasc Res, March 1, 1998; 37(3): 564 - 566. [Full Text] [PDF]

				R. Collins, R. Peto, C. Baigent, and P. Sleight Aspirin, Heparin, and Fibrinolytic Therapy in Suspected Acute Myocardial Infarction N. Engl. J. Med., March 20, 1997; 336(12): 847 - 860. [Full Text] [PDF]

				R. Collins, S. MacMahon, M. Flather, C. Baigent, L. Remvig, S. Mortensen, P. Appleby, J. Godwin, S. Yusuf, and R. Peto Clinical effects of anticoagulant therapy in suspected acute myocardial infarction: systematic overview of randomised trials BMJ, September 14, 1996; 313(7058): 652 - 659. [Abstract] [Full Text]

				D. Hasdai, N. Varda-Bloom, N. Blumberg, D. Ohad, R. Kornowski, and A. Battler The Effect of Low Molecular Weight Heparin (Fragmin) on Myocardial Neutrophil Accumulation and Infarct Size in a Rat Model of Myocardial Infarction Angiology, May 1, 1996; 47(5): 491 - 499. [Abstract] [PDF]

				C. B. Granger, J. Hirsh, R. M. Califf, J. Col, H. D. White, A. Betriu, L. H. Woodlief, K. L. Lee, E. G. Bovill, R. J. Simes, et al. Activated Partial Thromboplastin Time and Outcome After Thrombolytic Therapy for Acute Myocardial Infarction : Results From the GUSTO-I Trial Circulation, March 1, 1996; 93(5): 870 - 878. [Abstract] [Full Text]

				J. S. Mruk, P. Zoldhelyi, M. W.I. Webster, M. Heras, D. E. Grill, D. R. Holmes Jr, V. Fuster, and J. H. Chesebro Does Antithrombotic Therapy Influence Residual Thrombus After Thrombolysis of Platelet-Rich Thrombus? : Effects of Recombinant Hirudin, Heparin, or Aspirin Circulation, February 15, 1995; 93(4): 792 - 799. [Abstract] [Full Text]

				H. V. Anderson and J. T. Willerson Thrombolysis in Acute Myocardial Infarction N. Engl. J. Med., September 2, 1993; 329(10): 703 - 709. [Full Text]