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

OBJECTIVES The purpose of this study was to determine the incidence and dem ographic characteristics of patients experiencing cardiac rupture after thr ombolytic and adjunctive anticoagulant therapy and to identify possible ass ociations between the mechanism of thrombin inhibition (indirect, direct) a nd 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 a gents. Little is known about specific patient- and treatment-related risk f actors. METHODS Patients (n = 3,759) with MI participating in the Thrombolysis and Thrombin Inhibition in Myocardial Infarction 9A and B trials received intra venous thrombolytic therapy, aspirin and either heparin (5,000 U bolus, 1,0 00 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 ab sence of preceding congestive heart failure, slowly progressive hemodynamic compromise or malignant ventricular arrhythmias. RESULTS A total of 65 rupture events (1.7%) were repoaed-all were fatal and a majority occurred within 48 h of treatment. Patients with cardiac ruptur e were older, of lower bodyweight 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 (OR2.87; 95% CI 1.44, 5.73) and prior angina (OR 1.82; 95% CI 1.05, 3.16) were independently associated with cardiac rupture. Independen t 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 associat ion between the type of thrombin inhibition, the intensity of anticoagulati on and cardiac rapture. CONCLUSIONS Cardiac rupture following thrombolytic therapy tends to occur i n older patients and may explain the disproportionately high mortality rate among women in prior clinical trials. Unlike major hemorrhagic complicatio ns, there is no evidence that the intensity of anticoagulation associated w ith heparin or hirudin administration influences the occurrence of rupture. (C) 1999 by the American College of Cardiology.