15 August 1991

Hemorrhagic Events during Therapy with Recombinant Tissue-Type Plasminogen Activator, Heparin, and Aspirin for Acute Myocardial Infarction: Results of the Thrombolysis in Myocardial Infarction (TIMI), Phase II Trial

Publication: Annals of Internal Medicine
Volume 115, Number 4


Objectives: To assess the effects of invasive procedures, hemostatic and clinical variables, the timing of beta-blocker therapy, and the doses of recombinant plasminogen activator (rt-PA) on hemorrhagic events.
Design: A multicenter, randomized, controlled trial.
Setting: Hospitals participating in the Thrombolysis in Myocardial Infarction, Phase II trial (TIMI II).
Interventions: Patients received rt-PA, heparin, and aspirin. The total dose of rt-PA was 150 mg for the first 520 patients and 100 mg for the remaining 2819 patients. Patients were randomly assigned to an invasive strategy (coronary arteriography with percutaneous angioplasty [if feasible] done routinely 18 to 48 hours after the start of thrombolytic therapy) or to a conservative strategy (coronary arteriography done for recurrent spontaneous or exercise-induced ischemia). Eligible patients were also randomly assigned to either immediate intravenous or deferred beta-blocker therapy.
Measurements: Patients were monitored for hemorrhagic events during hospitalization.
Main Results: In patients on the 100-mg rt-PA regimen, major and minor hemorrhagic events were more common among those assigned to the invasive than among those assigned to the conservative strategy (18.5% versus 12.8%, P < 0.001). Major or minor hemorrhagic events were associated with the extent of fibrinogen breakdown, peak rt-PA levels, thrombocytopenia, prolongation of the activated partial thromboplastin time (APTT) to more than 90 seconds, weight of 70 kg or less, female gender, and physical signs of cardiac decompensation. Immediate intravenous beta-blocker therapy had no important effect on hemorrhagic events when compared with delayed beta-blocker therapy. Intracranial hemorrhages were more frequent among patients treated with the 150-mg rt-PA dose than with the 100-mg rt-PA dose (2.1% versus 0.5%, P < 0.001). The extent of the plasmin-mediated hemostatic defect was also greater in patients receiving the 150-mg dose.
Conclusions: Increased morbidity due to hemorrhagic complications is associated with an invasive management strategy in patients with acute myocardial infarction. Our findings show the complex interaction of several factors in the occurrence of hemorrhagic events during thrombolytic therapy.

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Information & Authors


Published In

cover image Annals of Internal Medicine
Annals of Internal Medicine
Volume 115Number 415 August 1991
Pages: 256 - 265


Published in issue: 15 August 1991
Published online: 1 December 2008




Michael L. Terrin, MD, MPH
Margaret Frederick, PhD
Costas T. Lambrew, MD
George Sopko, MD, MPH
Russell P. Tracy, PhD
James H. Chesebro, MD
From the University of Vermont College of Medicine, Burlington, Vermont; Maryland Medical Research Institute, Baltimore, Maryland; Columbia University and New York University, New York, New York; University of Massachusetts Medical School, Worcester, Massachusetts; University of Texas Southwestern Medical Center, Dallas, Texas; Maine Medical Center, Portland, Maine; George Washington University, Washington, DC; Harvard Medical School, Boston, Massachusetts; Baylor College of Medicine, Houston, Texas; University of Minnesota, Minneapolis, Minnesota; National Heart, Lung, and Blood Institute, Bethesda, MD; and Mayo Clinic, Rochester, Minnesota. For current author addresses, see end of text.
For a listing of the investigators and centers participating in the TIMI II trial, see reference 15.

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Edwin G. Bovill, Michael L. Terrin, David C. Stump, et al. Hemorrhagic Events during Therapy with Recombinant Tissue-Type Plasminogen Activator, Heparin, and Aspirin for Acute Myocardial Infarction: Results of the Thrombolysis in Myocardial Infarction (TIMI), Phase II Trial. Ann Intern Med.1991;115:256-265. doi:10.7326/0003-4819-115-4-256

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