Challenging the validity of imposing contraindications to thrombolysis for acute ischemic stroke

A colleague once challenged grand rounds attendants to identify any pharmacologic treatment for stroke, other than recombinant tissue plasminogen activator (rtPA), which, 15 years after Food and Drug Administration approval, still evoked a mental checklist of eligibility criteria, with numerous contraindications, yet the audience was mute. Are all IV thrombolysis exclusion criteria really necessary? The Simplified Management of Acute Stroke Using Revised Treatment (SMART) protocol considers all ischemic stroke patients for thrombolysis regardless of common rtPA exclusion criteria, contending that such criteria are consensus-based, not evidence-based; nearly 20% of all ischemic stroke patients received IV rtPA without an increase in adverse events.1 SMART proposed that exclusion criteria be critically reevaluated,1 with many investigators adopting an empirical approach to this challenge.2,3 Concerns over poorer post-thrombolysis outcomes in patients with a history of prior stroke and diabetes prompted trialists to exclude these patients for the European Cooperative Acute Stroke Study (ECASS)–3.4 Prior stroke reduces the benefits from thrombolysis.5 Furthermore, there is a clear association of hyperglycemia with worse outcomes in ischemic stroke, through multiple possible mechanisms6: increased plasminogen activator inhibitor-1 activity, resistance to antithrombotic agents, and …