Thrombolysis.

Abstract

The most widely studied thrombolytic drugs in stroke have been streptokinase (SK) and alteplase. The three large trials with streptokinase were terminated prematurely. The combined results reveal an early increased risk of cerebral haemorrhage and death, with no net benefit at final follow-up, even in subgroups. Some controversy persists, however. The dose may have been inappropriately high, very early treatment has not been fully tested, and concomitant use of aspirin or heparin may have contributed to the deleterious effect. Even so, there is no evidence to guide the choice of a lower dose, streptokinase predisposes to a prolonged anticoagulant effect, and is associated with hypotension which may offset any benefit. The four large alteplase trials in acute stroke were more encouraging. The NINDS study was clearly positive and supporting evidence comes from the two ECASS trials when subjected to meta-analysis. The trials have shown additional functional recovery in 0.6% of patients receiving SK within 6 h and in 7.6% with alteplase, at the expense of excess mortality of 1.1% for alteplase and 11.7% for SK. There was an absolute cerebral haemorrhage excess of 10.7% with SK and 8% for alteplase. If alteplase use is restricted to < 3 h from stroke onset, the NNT is 10.7 with no excess mortality; later treatment (3-6 h) gives an NNT of 26 and absolute mortality of 3.4%. Finally, early fibrinogen depletion with ancrod also appears to have beneficial effects when treatment is started within 3 h of stroke onset. Further trials are still required to establish, inter alia, the outer limit of the therapeutic window, to identify sub-groups of patients in whom clear benefit (or harm) exists and to establish appropriate management protocols for concomitant treatment. Thrombolysis with alteplase within 3 h of stroke onset may be considered for patients in whom haemorrhage and established infarction have been excluded. Trained assessment is essential, since there is an increased risk of haemorrhagic conversion that may be fatal. Patients considering thrombolytic treatment should appreciate that 1 in 10 patients have improved outcome, 1 in 20 suffer haemorrhagic conversion and 1 in 100 may die as a result of treatment. Treatment much later than 3 h from stroke onset in unselected patients is as likely to kill as to cure.