April 1, 2019

Background: No matter which side of the debate you sit on in regard to systemic thrombolysis in acute ischemic stroke (AIS), there is one truth: systems have undergone major changes to ensure tPA is offered to patients in the ≤4.5-hour window.  The debate surrounding tPA in AIS lies in the equipoise surrounding benefits while there are very real harms.  Advocates of tPA in AIS hang on to two trials that have never been replicated (i.e. NINDS and ECASS-III), and both have major methodological issues. Skeptics of tPA in AIS appropriately argue that there are 11 other randomized clinical trials which have shown almost no benefit, but come at the cost of early increased early mortality and symptomatic intracranial hemorrhage (sICH) (Nice breakdown of individual trials of thrombolysis in stroke can be found at First10EM).  Now there is a push to extend the window of tPA out to 9 hours in AIS with newer imaging modalities such as MRI diffusion-weighted studies in patients with unknown onset of symptoms. The push for this stems from the fact that patients with a visible ischemic lesion on diffusion-weighted imaging, combined with the absence of a clearly visible hyperintense signal in the same region on fluid-attenuated inversion recovery (FLAIR) is predictive of symptom onset within 4.5 hours before imaging.

September 6, 2018

Background: Despite serious concerns about the role of alteplase in the management of acute ischemic stroke including, but not limited to, significant conflicts of interest, unbalanced baseline patient characteristics, systematic devaluation of contrary data, lack of reproduced benefit and low fragility index, it remains standard care for patients presenting with symptoms of acute ischemic stroke within 3 (or 4.5 depending on system) hours of onset of symptoms. Though the NINDS studies only showed benefit in a specific subgroup of patients, subsequent work has endeavored to expand the target group in a classic example of indication creep. Patients with minor CVA (NIHSS < 5 without disabling features or, essentially mRS 0-1) represent one such subgroup in which alteplase is often not employed due mainly in part to the perception of minimal benefit with continued potential for harm (i.e. anaphylaxis, intracranial hemorrhage). Alteplase supporters argue that minor stroke patients should still get the drug as it not only may reduce symptoms but can also prevent deterioration. The evidence for this viewpoint is both extremely limited and of poor methodologic quality.

June 4, 2018

Background: Alteplase is a tissue plasminogen activator that is approved for use prior to thrombectomy in ischemic strokes with the goal of reperfusion to ischemic areas of the brain. Tenecteplase is a recombinant enzyme derived from alteplase that is more specific to fibrin and more resistant to inactivation by alteplase inhibitors. Tenecteplase is less expensive, can be administered at a faster rate than alteplase and has a longer half-life allowing for bolus dosing. Prior studies have shown similar to better outcomes with use of tenecteplase versus alteplase in patients with ischemic stroke.

May 26, 2016

Background: Despite continued debate on the efficacy of alteplase (tPA), it currently remains one of the major interventions directed at patients presenting with acute ischemic stroke. The current standard dose of the drug is 0.9 mg/kg given over 1 hour. It is unclear whether lower doses would be equally effective in increasing good neurologic outcomes after stroke while simultaneously decreasing the rate of intracerebral hemorrhage (ICH); the most serious side effect. Evidence showing that lower doses of tPA are non-inferior to standard-dose tPA could lead to a shift in treatment.