CLINICAL STUDIES
Fatal cardiac rupture among patients treated with thrombolytic agents and adjunctive thrombin antagonists
Observations from the Thrombolysis and Thrombin Inhibition in Myocardial Infarction 9 Study
Richard C. Becker, MD*,
Judith S. Hochman, MD ,
Christopher P. Cannon, MD ,
Frederick A. Spencer, MD*,
Steven P. Ball, RN*,
Michael J. Rizzo ,
Elliott M. Antman, MD for the TIMI 9 Investigators
* Cardiovascular Thrombosis Research Center, University of Massachusetts Medical School, Worcester, Massachusetts, USA
St. Luke’s/Roosevelt Hospital Center, Columbia University, College of Physicians and Surgeons, New York, New York, USA
Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
TIMI Database and Coordinating Center, Veterans Administration Medical Center, West Roxbury, Massachusetts, USA
Manuscript received April 28, 1998;
revised manuscript received September 10, 1998,
accepted October 22, 1998.
Reprint requests and correspondence: Richard C. Becker, MD, Cardiovascular Thrombosis Research Center, University of Massachusetts Medical School, Worcester, Massachusetts 01655-0214
Becker{at}Banyan.Ummed.edu
Objectives
The purpose of this study was to determine the incidence and demographic characteristics of patients experiencing cardiac rupture after thrombolytic and adjunctive anticoagulant therapy and to identify possible associations between the mechanism of thrombin inhibition (indirect, direct) and the intensity of systemic anticoagulation with its occurrence.
Background
Cardiac rupture is responsible for nearly 15% of all in-hospital deaths among patients with myocardial infarction (MI) given thrombolytic agents. Little is known about specific patient- and treatment-related risk factors.
Methods
Patients (n = 3,759) with MI participating in the Thrombolysis and Thrombin Inhibition in Myocardial Infarction 9A and B trials received intravenous thrombolytic therapy, aspirin and either heparin (5,000 U bolus, 1,000 to 1,300 U/h infusion) or hirudin (0.1 to 0.6 mg/kg bolus, 0.1 to 0.2 mg/kg/h infusion) for at least 96 h. A diagnosis of cardiac rupture was made clinically in patients with sudden electromechanical dissociation in the absence of preceding congestive heart failure, slowly progressive hemodynamic compromise or malignant ventricular arrhythmias.
Results
A total of 65 rupture events (1.7%) were reported—all were fatal, and a majority occurred within 48 h of treatment. Patients with cardiac rupture were older, of lower body weight and stature and more likely to be female than those without rupture (all p < 0.001). By multivariable analysis, age >70 years (odds ratio [OR] 3.77; 95% confidence interval [CI] 2.06, 6.91), female gender (OR 2.87; 95% CI 1.44, 5.73) and prior angina (OR 1.82; 95% CI 1.05, 3.16) were independently associated with cardiac rupture. Independent predictors of nonrupture death included age >70 years (OR 3.68; 95% CI 2.53, 5.35) and prior MI (OR 2.14; 95%, CI 1.45, 3.17). There was no association between the type of thrombin inhibition, the intensity of anticoagulation and cardiac rapture.
Conclusions
Cardiac rupture following thrombolytic therapy tends to occur in older patients and may explain the disproportionately high mortality rate among women in prior clinical trials. Unlike major hemorrhagic complications, there is no evidence that the intensity of anticoagulation associated with heparin or hirudin administration influences the occurrence of rupture.
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Abbreviations and Acronyms
| | ACE | = angiotensin-converting enzyme | | aPTT | = activated partial thromboplastin time | | CI | = confidence interval | | MI | = myocardial infarction | | NRMI-1 | = National Registry of Myocardial Infarction | | OR | = odds ratio | | TIMI | = Thrombolysis and Thrombin Inhibition in Myocardial Infarction | | tPA | = tissue plasminogen activator |
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