June 3, 2019

Background: Despite the lack of replication of the NINDS & ECASS-3 trials, guidelines recommend the use of tPA in the ≤4.5hr window after the onset of symptoms of acute ischemic stroke [2]. These recommendations used non-contrast computed tomography (NCHCT) for the selection of patients.  More recent endovascular studies have shown that perfusion-based imaging can show potential viable brain tissue beyond the 4.5 hour mark in patients with large vessel occlusions and result in good neurologic outcomes.  This advance has prompted investigators to look at perfusion-based technology to identify a larger cohort of patients without large vessel occlusion that may be candidates for systemic thrombolysis.  One of the big fears in stroke management is the concept of indication creep: finding more uses for a medication or product without strong evidence to support its use. The bigger question is, does this increase in use help the company’s bottom line or the patient? It is no wonder physicians are skeptical of industry sponsored trials, as we sometimes question the motives behind the study.  Now we have another industry sponsored trial: EXTEND. In this trial.

April 11, 2019

The shiny new toy in stroke treatment is endovascular therapy.  There have now been 12 randomized controlled trials (RCTs) on endovascular stroke therapy (EST), with eight of the last nine showing positive results – stunningly positive.  This flood of positive trials has led to new guidelines from the American Heart Association (AHA) and American Stroke Association (ASA)that extend the treatment window potentially as far out as 24 hours after last known well, and has spawned a movement to completely overhaul how we deliver care for patients with acute ischemic stroke (AIS). With all of the enthusiasm for EST, it is important to review the evolution of this new approach, to review and critique the evidence, and to evaluate what this means in clinical practice.

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.

April 22, 2018

With the publication of the DAWN and DEFUSE-3 trials came a new era in stroke management.  We have discussed the specific literature pertaining to endovascular therapy on REBEL EM before in our 2hour CME activity HERE.  Along with the two new publications came the 2018 AHA/ASA guidelines for endovascular therapy in acute ischemic stroke.  Anand Swaminathan and myself wanted to place a stand alone post on the workflow of stroke in 2018.