Chirantan Banerjee, MD
Muchada M, Rodriguez-Luna D, Pagola J, Flores A, Sanjuan E, Meler P, et al. Impact of Time to Treatment on Tissue-Type Plasminogen Activator–Induced Recanalization in Acute Ischemic Stroke. Stroke. 2014
The importance of time in hyperacute stroke care cannot be emphasized enough. In the NINDS tPA trial, the odds of a good functional outcome with IV tPA dropped from 2.6 if given between 0 – 90 min to 1.2 when given 271 – 360 min. Similarly, the NNT increased from 4.5 to 21.4. In the IMS-III trial, one of the major messages that emerged from the data was again that delays in time to angiographic reperfusion lead to a decreased likelihood of good clinical outcome in patients after moderate to severe stroke. With every step we take towards advancing acute stroke care, the importance of time to reperfusion keeps coming up again and again.
Now that the effect of time on functional outcome has been established, one interesting question that I have always had is that does delay in tPA delivery fail to improve outcomes with time because the brain tissue is not salvageable anymore, or that its efficacy to recanalize suffers as the clot matures, or a combination of the two. Muchada et al in the current issue of Stroke aimed to assess the influence of time on tPA induced recanalization in acute stroke patients. 508 consecutive acute stroke patients with proven MCA occlusions by TCD and who received IV tPA up to 4.5 hours, as well as ~6% who received tPA between 4.5 – 6 hours (selected by penumbral imaging) were included. Mean time to treatment was 171 min over the 7 year study period. TCD was repeated 1 hour post tPA. Any improvement in the TCD signal was considered to indicate recanalization. There was no linear association between time-to-treatment and recanalization. However, when converted to sequential 30 min time-to-treatment windows, as well as when dichotomized to <=270 min or >270 min, recanalization was seen to decrease with time. Several findings in the study corroborate with prior data.
Overall recanalization rate of 36% is consistent with 30-40% previously reported. Also, higher NIHSS score, hyperglycemia, older age and female sex were again seen to decrease chance of recanalization. Proximal MCA occlusions had a trend towards lower recanalization rate, especially after the first 90 min, in synergy with previous reports. Distal occlusions had a recanalization rate ~30% regardless of time. The main limitation of the study is the measurement bias associated with use of TCD to assess vessel status. Also, the fact that only 6% patients received tPA >270 minutes affects the distribution of data. Some variables such as pre-treatment ASPECTS which have been previously shown to affect recanalization status were not included in the model.
This study again emphasizes the importance of time in acute stroke care, and finds poor recanalization outcomes beyond 270 min for proximal MCA occlusions. The authors argue that IV thrombolysis may be insufficient beyond this window, and more aggressive therapies should be explored. The critical question is, would it even matter if you do recanalize the occluded vessel at that point, or has the ship sunk already!