Comparison of high-dose with low-dose subcutaneous heparin to prevent left ventricular mural thrombosis in patients with acute transmural anterior myocardial infarction
AG Turpie, JG Robinson, DJ Doyle, AS Mulji, GJ Mishkel, BJ Sealey, JA Cairns, L Skingley, J Hirsh, and M Gent
We performed a double-blind randomized trial comparing high doses of subcutaneous heparin (12,500 units every 12 hours) with low doses (5000 units every 12 hours) for 10 days in the prevention of left ventricular mural thrombosis in 221 patients with acute anterior myocardial infarction. Left ventricular mural thrombosis was observed by two-dimensional echocardiography on the 10th day after infarction in 10 of 95 patients (11 percent) in the high-dose group and in 28 of 88 patients (32 percent) in the low-dose group (P = 0.0004). One patient in the high-dose group and four in the low-dose group had nonhemorrhagic strokes (P = 0.17). One patient in the low-dose group had a fatal pulmonary embolism. There was no difference in the frequency of hemorrhagic complications, which occurred in six patients in the high-dose group and four in the low-dose group. The mean (+/- SEM) plasma heparin concentration was 0.18 +/- 0.017 U per milliliter in the high-dose group and 0.01 +/- 0.005 U per milliliter in the low-dose group (P less than 0.0001). In the high-dose group, the mean plasma heparin concentration was 0.10 +/- 0.029 U per milliliter among patients with abnormal two-dimensional echocardiograms, as compared with 0.19 +/- 0.019 U per milliliter among patients with normal echocardiograms (P = 0.01). We conclude that heparin administered subcutaneously in a dosage of 12,500 units every 12 hours to patients with acute anterior transmural myocardial infarction is more effective than a lower dosage (5000 units every 12 hours) in preventing left ventricular mural thrombosis.
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Department of Medicine, McMaster University, Hamilton, Ont., Canada.
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Anand, S., Ginsberg, J. S., Hirsh, J.
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Mooe, T., Eriksson, P., Stegmayr, B.
(1997). Ischemic Stroke After Acute Myocardial Infarction : A Population-Based Study. Stroke
28: 762-767
[Abstract][Full Text]
Deedwania, P. C., Amsterdam, E. A., Vagelos, R. H.
(1997). Evidence-Based, Cost-effective Risk Stratification and Management After Myocardial Infarction. Arch Intern Med
157: 273-280
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Loh, E., Sutton, M. St. J., Wun, C.-C. C., Rouleau, J. L., Flaker, G. C., Gottlieb, S. S., Lamas, G. A., Moye, L. A., Goldhaber, S. Z., Pfeffer, M. A.
(1997). Ventricular Dysfunction and the Risk of Stroke after Myocardial Infarction. NEJM
336: 251-257
[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]
Raschke, R. A., Gollihare, B., Peirce, J. C.
(1996). The Effectiveness of Implementing the Weight-Based Heparin Nomogram as a Practice Guideline. Arch Intern Med
156: 1645-1649
[Abstract]
Pearson, S. D., Polak, J. L., Cartwright, S., McCabe-Hassan, S., Lee, T. H., Goldhaber, S. Z.
(1995). A Critical Pathway to Evaluate Suspected Deep Vein Thrombosis. Arch Intern Med
155: 1773-1778
[Abstract]
Granger, C. B., Miller, J. M., Bovill, E. G., Gruber, A., Tracy, R. P., Krucoff, M. W., Green, C., Berrios, E., Harrington, R. A., Ohman, E. M., Califf, R. M.
(1995). Rebound Increase in Thrombin Generation and Activity After Cessation of Intravenous Heparin in Patients With Acute Coronary Syndromes. Circulation
91: 1929-1935
[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]
Levine, M. N., Hirsh, J., Gent, M., Turpie, A. G., Leclerc, J., Powers, P. J., Jay, R. M., Neemeh, J.
(1991). Prevention of Deep Vein Thrombosis after Elective Hip Surgery: A Randomized Trial Comparing Low Molecular Weight Heparin with Standard Unfractionated Heparin. ANN INTERN MED
114: 545-551
[Abstract]
Becker, R. C., Alpert, J. S.
(1990). The Impact of Medical Therapy on Hemorrhagic Complications Following Coronary Artery Bypass Grafting. Arch Intern Med
150: 2016-2021
[Abstract]
Gore, J. M., Dalen, J. E.
(1990). Cardiovascular Disease. JAMA
263: 2629-2631
[Abstract]
(1989). Cardiogenic Brain Embolism: The Second Report of the Cerebral Embolism Task Force. Arch Neurol
46: 727-743
[Abstract]