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
J Hsia, WP Hamilton, N Kleiman, R Roberts, BR Chaitman, and AM Ross
BACKGROUND. We report the results of the Heparin-Aspirin Reperfusion Trial, a collaborative study comparing early intravenous heparin with oral aspirin as adjunctive treatment when recombinant tissue plasminogen activator (rt-PA) is used for coronary thrombolysis during acute myocardial infarction. METHODS. Two hundred five patients were randomly assigned to receive either immediate and then continuous intravenous heparin (starting with a 5000-unit bolus; n = 106) or immediate and then daily oral aspirin (80 mg; n = 99) together with rt-PA (100 mg intravenously over a six-hour period) initiated within six hours of the onset of symptoms. We evaluated the patency of the infarct-related artery by angiography 7 to 24 hours after beginning rt-PA infusion, the frequency of reocclusion of the artery by repeat angiography on day 7, and ischemic or hemorrhagic complications during the hospital stay. RESULTS. At the time of the first angiogram, 82 percent of the infarct-related arteries in the patients assigned to heparin were patent, as compared with only 52 percent in the aspirin group (P less than 0.0001). Of the initially patent vessels, 88 percent remained patent after seven days in the heparin group, as compared with 95 percent in the aspirin group (P not significant). The numbers of hemorrhagic events (18 in the heparin and 15 in the aspirin group) and recurrent ischemic events (8 in the heparin and 2 in the aspirin group) were similar in the two groups. CONCLUSIONS. Coronary patency rates associated with rt-PA are higher with early concomitant systemic heparin treatment than with concomitant low-dose oral aspirin. This observation has important implications for clinical practice and should be considered in the design and interpretation of clinical trials involving coronary thrombolytic therapy.
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Department of Medicine, George Washington University, Washington, DC 20037.
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[Abstract][Full Text]
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(2002). Improved reperfusion and clinical outcome with enoxaparin as an adjunct to streptokinase thrombolysis in acute myocardial infarction. The AMI-SK study. Eur Heart J
23: 1282-1290
[Abstract]
Coussement, P.K, Bassand, J.-P, Convens, C, Vrolix, M, Boland, J, Grollier, G, Michels, R, Vahanian, A, Vanderheyden, M, Rupprecht, H.-J, Van de Werf, F
(2001). A synthetic factor-Xa inhibitor (ORG31540/SR9017A) as an adjunct to fibrinolysis in acute myocardial infarction. The PENTALYSE study. Eur Heart J
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[Abstract]
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(2001). 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). Circulation
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[Abstract][Full Text]
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(2001). Guide to Anticoagulant Therapy: Heparin : A Statement for Healthcare Professionals From the American Heart Association. Arterioscler. Thromb. Vasc. Bio.
21
: e9-e9
[Full Text]
Hirsh, J., Anand, S. S., Halperin, J. L., Fuster, V.
(2001). Guide to Anticoagulant Therapy: Heparin : A Statement for Healthcare Professionals From the American Heart Association. Circulation
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[Full Text]
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(2001). Treatment of Reinfarction After Thrombolytic Therapy for Acute Myocardial Infarction : An Analysis of Outcome and Treatment Choices in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO I) and Assessment of the Safety of a New Thrombolytic (ASSENT 2) Studies. Circulation
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[Abstract][Full Text]
Ohman, E. M., Harrington, R. A., Cannon, C. P., Agnelli, G., Cairns, J. A., Kennedy, J.W.
(2001). Intravenous Thrombolysis in Acute Myocardial Infarction. Chest
119
: 253S-277S
[Full Text]
Goldman, L. E., Eisenberg, M. J.
(2000). Identification and Management of Patients with Failed Thrombolysis after Acute Myocardial Infarction. ANN INTERN MED
132: 556-565
[Abstract][Full Text]
Awtry, E. H., Loscalzo, J.
(2000). Aspirin. Circulation
101: 1206-1218
[Full Text]
Iqbal, O., Messmore, H., Hoppensteadt, D., Fareed, J., Wehrmacher, W.
(2000). State-of-the-Art Review : Thrombolytic Drugs in Acute Myocardial Infarction. CLIN APPL THROMB HEMOST
6: 1-13
Cannon, C. P.
(1999). Overcoming thrombolytic resistance: Rationale and initial clinical experience combining thrombolytic therapy and glycoprotein IIb/IIIa receptor inhibition for acute myocardial infarction. J Am Coll Cardiol
34: 1395-1402
[Abstract][Full Text]
Jang, I.-K., Brown, D. F. M., Giugliano, R. P., Anderson, H. V., Losordo, D., Nicolau, J. C., Dutra, O. P., Bazzino, O., Viamonte, V. M., Norbady, R., Liprandi, A. S., Massey, T. J., Dinsmore, R., Schwarz, R. P. Jr, the MINT Investigators,
(1999). A multicenter, randomized study of argatroban versus heparin as adjunct to tissue plasminogen activator (TPA) in acute myocardial infarction: myocardial infarction with Novastan and TPA (MINT) study. J Am Coll Cardiol
33: 1879-1885
[Abstract][Full Text]
Bednar, M. M., Gross, C. E.
(1999). Antiplatelet Therapy in Acute Cerebral Ischemia. Stroke
30: 887-893
[Abstract][Full Text]
Bates, S. M., Weitz, J. I.
(1999). Prevention of activation of blood coagulation during acute coronary ischemic syndromes: beyond aspirin and heparin. Cardiovasc Res
41: 418-432
[Abstract][Full Text]
Chamuleau, S A J, de Winter, R J, Levi, M, Adams, R, Büller, H R, Prins, M H, Lie, K I, Peters, R J G
(1998). Low molecular weight heparin as an adjunct to thrombolysis for acute myocardial infarction: the FATIMA study. Heart
80: 35-39
[Abstract][Full Text]
Mungall, D., Baker, B. A., Adelman, M. D.
(1998). Activated Partial Thromboplastin Time vs Heparin Concentration. Arch Intern Med
158: 1273-1275
[Full Text]
White, R. L
(1998). Thrombolytic Therapy in Acute Myocardial Infarction Part II: 1997 Update. Asian Cardiovasc. Thorac. Ann.
6: 03-10
[Abstract][Full Text]
Pickering, W., Brozovic, M., Dancy, M., Cohen, H.
(1997). Thrombolysis, With or Without Heparin, During the First Nine Weeks After Acute Myocardiat Infarction. CLIN APPL THROMB HEMOST
3: 183-189
[Abstract]
McKenzie, C. R., Abendschein, D. R., Eisenberg, P. R.
(1996). Sustained Inhibition of Whole-Blood Clot Procoagulant Activity by Inhibition of Thrombus-Associated Factor Xa. Arterioscler. Thromb. Vasc. Bio.
16: 1285-1291
[Abstract][Full Text]
Collins, R., MacMahon, S., Flather, M., Baigent, C., Remvig, L., Mortensen, S., Appleby, P., Godwin, J., Yusuf, S., Peto, R.
(1996). Clinical effects of anticoagulant therapy in suspected acute myocardial infarction: systematic overview of randomised trials. BMJ
313: 652-659
[Abstract][Full Text]
Schaer, G. L., Spaccavento, L. J., Browne, K. F., Krueger, K. A., Krichbaum, D., Phelan, J. M., Fletcher, W. O., Grines, C. L., Edwards, S., Jolly, M. K., Gibbons, R. J.
(1996). Beneficial Effects of RheothRx Injection in Patients Receiving Thrombolytic Therapy for Acute Myocardial Infarction: Results of a Randomized, Double-Blind, Placebo-Controlled Trial. Circulation
94: 298-307
[Abstract][Full Text]
Yao, S.-K., Akhtar, S., Scott-Burden, T., Ober, J. C., Golino, P., Buja, L. M., Casscells, W., Willerson, J. T.
(1995). Endogenous and Exogenous Nitric Oxide Protect Against Intracoronary Thrombosis and Reocclusion After Thrombolysis. Circulation
92: 1005-1010
[Abstract][Full Text]
Simes, R.J., Topol, E. J., Holmes, D. R. Jr, White, H. D., Rutsch, W. R., Vahanian, A., Simoons, M. L., Morris, D., Betriu, A., Califf, R. M., Ross, A. M.
(1995). Link Between the Angiographic Substudy and Mortality Outcomes in a Large Randomized Trial of Myocardial Reperfusion : Importance of Early and Complete Infarct Artery Reperfusion. Circulation
91: 1923-1928
[Abstract][Full Text]
Gunnarsson, P. S., Sawyer, W. T., Montague, D., Williams, M. L., Dupuis, R. E., Caiola, S. M.
(1995). Appropriate Use of Heparin: Empiric vs Nomogram-Based Dosing. Arch Intern Med
155: 526-532
[Abstract]
Leya, F., Fareed, J., Walenga, J.
(1995). Acute Myocardial Infarction: Diagnosis and Management. CLIN APPL THROMB HEMOST
1: 160-165
[Abstract]
Mruk, J. S., Zoldhelyi, P., Webster, M. W.I., Heras, M., Grill, D. E., Holmes, D. R. Jr, Fuster, V., Chesebro, J. H.
(1995). Does Antithrombotic Therapy Influence Residual Thrombus After Thrombolysis of Platelet-Rich Thrombus? : Effects of Recombinant Hirudin, Heparin, or Aspirin. Circulation
93: 792-799
[Abstract][Full Text]
Flaker, G. C., Bartolozzi, J., Davis, V., McCabe, C., Cannon, C. P.
(1994). Use of a Standardized Heparin Nomogram to Achieve Therapeutic Anticoagulation After Thrombolytic Therapy in Myocardial Infarction. Arch Intern Med
154: 1492-1496
[Abstract]
The GUSTO Investigators,
(1993). An International Randomized Trial Comparing Four Thrombolytic Strategies for Acute Myocardial Infarction. NEJM
329: 673-682
[Abstract][Full Text]
Anderson, H. V., Willerson, J. T.
(1993). Thrombolysis in Acute Myocardial Infarction. NEJM
329: 703-709
[Full Text]
(1992). Adult Advanced Cardiac Life Support. JAMA
268: 2199-2241
[Abstract]
Pfeffer, M. A., Moye, L. A., Braunwald, E., Basta, L., Brown, E. J. Jr, Cuddy, T. E., Dagenais, G. R., Flaker, G. C., Geltman, E. M., Gersh, B. J., Goldman, S., Lamas, G. A., Packer, M., Rouleau, J. L., Rutherford, J. D., Steingart, R. M., Wertheimer, J. H.
(1991). Selection Bias in the Use of Thrombolytic Therapy in Acute Myocardial Infarction. JAMA
266: 528-532
[Abstract]
Popma, J. J., Topol, E. J.
(1991). Adjuncts to Thrombolysis for Myocardial Reperfusion. ANN INTERN MED
115: 34-44
[Abstract]
Gore, J. M., Dalen, J. E.
(1991). Cardiovascular Disease. JAMA
265: 3105-3107
[Abstract]
Sherry, S., Marder, V. J.
(1991). Streptokinase and Recombinant Tissue Plasminogen Activator (rt-PA) Are Equally Effective in Treating Acute Myocardial Infarction. ANN INTERN MED
114: 417-423
[Abstract]
Antman, E. M., Louwerenburg, H. W., Baars, H. F., Wesdorp, J. C.L., Hamer, B., Bassand, J.-P., Bigonzi, F., Pisapia, G., Gibson, C. M., Heidbuchel, H., Braunwald, E., Van de Werf, F., for the ENTIRE-TIMI 23 Investigators,
(2002). Enoxaparin as Adjunctive Antithrombin Therapy for ST-Elevation Myocardial Infarction: Results of the ENTIRE-Thrombolysis in Myocardial Infarction (TIMI) 23 Trial. Circulation
105: 1642-1649
[Abstract][Full Text]