Thrombolytic therapy for stroke: a review with particular reference to elderly patients

Clinical trials in the 1990s of intravenous thrombolysis for ischaemic stroke have involved over 3000 patients. Alteplase given within 3 hours of onset significantly reduces the combined end-point of death and disability. Although alteplase appears safe when given up to 6 hours after onset, individual trials have failed to confirm efficacy beyond 3 hours. Meta-analysis indicates that intravenous alteplase given up to 6 hours after stroke onset significantly reduces death or dependence 3 months after stroke. Two trials of intra-arterial pro-urokinase confirm benefits of treatment up to 6 hours in highly selected patients with angiographically confirmed proximal middle cerebral occlusion. Streptokinase increased the risk of early death significantly in 3 trials, with no overall reduction in eventual death and disability. Patients over 80 years have been excluded from most trials of alteplase, and experience in this age group is minimal. Increased incidence and poorer functional outcome in the elderly mean that thrombolysis may have greater absolute benefit in this group than in the young, but there is also a higher prevalence of absolute or relative potential contraindications to treatment (ranging from increased use of anticoagulant drugs to higher prevalence of atrial fibrillation). Further trials are necessary to address age restrictions and other important issues in the use of alteplase. Thrombolysis is likely to remain feasible for a minority of stroke patients of all ages, and there is a need for other acute treatment options.