Advances in Emerging Therapies

Abstract

Historically, stroke has proven to be a condition poorly amenable to treatment, and the last year delivered its share of neutral results in this regard. However, other studies suggested promising areas for pursuit while a couple grabbed the headlines and will modify clinical practice. We can justifiably emphasize the findings of the third European Cooperative Acute Stroke Study (ECASS-3), which has recently confirmed the use of thrombolytic therapy up to 4.5 hours after onset of ischemic stroke.1 The reality is that alteplase was already a safe and highly effective treatment before the results of ECASS-3 became known. However, a minority allowed their uncertainty over safety and doubts raised by individually neutral trials to restrict implementation of this potent therapy. The latest result broadens the range of patients who may benefit but it has implications beyond these narrow confines. Even after accounting for the expected low rate of symptomatic bleeding—just 2% excess over placebo—alteplase treatment delivered a 10% absolute increase in proportion of patients attaining excellent outcome, indicating 3 valuable lessons. First, any residual doubts over the safety or efficacy of intravenous alteplase early after stroke have been annulled. Second, the challenging time window for treatment can be relaxed, provided this is not at the expense of slower reaction by services. Third, there is evidently scope for further extension of treatment and enhancement of alteplase’s action that begs continued research. We need to test extended patient selection, perhaps via imaging strategies. We must also assess whether we can enhance the extent and rapidity of reperfusion. This may involve incoorporating ancillary measures such as antithrombotic therapy and blood pressure manipulation. One of our challenges is to divorce enhancement of reperfusion from exacerbation of serious bleeding risk. Both better patient selection and careful pharmacological profiling are required. By harnessing our very active …