Causal Connections and Clinical Implications

T he TIMI-9A1 and GUSTO-11A2 trial preliminary reports, in this issue of Circulation by highly experienced and respected investigators, show unexpectedly high rates of intracranial bleeds (ICBs) associated with administration of two plasminogen activators (streptokinase [SK] and tissue-type plasminogen activator [TPAI) and two intravenously administered anticoagulants (heparin and hirudin). Another report in this issue by equally outstanding researchers shows an increased risk of ICBs with hirudin compared with heparin, in combination with TPA,3 and no ICBs with TPA in combination with heparin. Cognizance by clinicians of these important observations, however, is not sufficient, particularly in a climate in which simplistic interpretations can inhibit illumination of mechanisms responsible and uncritical extrapolations can compromise patient care. By contrast, elucidation of specific causal connections will undoubtedly result in greater efficacy and safety in the use of anticoagulants accompanying coronary thrombolysis.