Yasmin Aziz, MD

International Stroke Conference 2022
February 9–11, 2022
Session: ‘Cocktails Anyone?’ Intravenous Thrombolysis Symposium

The 2022 International Stroke Conference moderated debates kicked off on Wednesday morning, February 9, with an ode to everyone’s favorite cocktail in New Orleans: thrombolytics.

Dr. Maarten Lansberg was the first to speak, arguing that any patient who meets extended window criteria for alteplase, whether by DWI-FLAIR mismatch or by CTP mismatch, should be eligible to receive treatment. After citing data from WAKE-UP and EXTEND, Dr. Laansberg presented evidence from two large meta-analyses showing favorable functional 90-day outcomes, in patients selected by MRI or by CTP, when treated with alteplase over placebo.1, 2 He concluded by stating that while the AHA/ASA guidelines cite only DWI-FLAIR mismatch with unclear last known normal time for alteplase administration, the Australian stroke guidelines mention either a DWI-FLAIR mismatch or a CTP mismatch for extended window administration. His conclusion was that all patients ineligible for thrombectomy presenting within 12 hours of last known normal time should be considered for extended window alteplase if a mismatch in either modality is found.

Dr. Bruce Campbell was next to respond, arguing that only certain patients should be offered thrombolytics in the extended time window. He began by going back to the meta-analysis cited by Dr. Lansberg,1 highlighting that the clear benefit of extended window lytics was only appreciated in patients with automated perfusion imaging identifying a mismatch >10cc, a mismatch ratio >1.2, and an overall core size of <70cc compared to less reliable visual assessment. Importantly, when this mismatch exists up to 9hrs from last known normal time (or 9hrs from midpoint of sleep), providers need to carefully analyze the non-contrast CTH to exclude hypodensity. He acknowledged that data is lacking for extended window lytic administration in thrombectomy-eligible patients (pending results of TIMELESS and ETERNAL), as well as for tenecteplase in general after 4.5 hours. Finally, he emphasized that MRI should only be used to identify patients with unknown last known normal time who may fit within the 0-4.5 hour timeframe, rather than patients known to be >4.5 hours.

Interestingly, a poll from the audience showed that only half of the providers in the audience were routinely screening for extended window lytic administration. Dr. James Grotta, the co-moderator with Dr. Steven Warach, questioned whether this was due to a perception that lytics are less effective in this timeframe. Audience members were curious how to practically perform bedside consent for extended window thrombolytics and whether the clock should be abandoned altogether with imaging-based selection. After a robust discussion, the moderators concluded that simpler guidelines on when and whom to screen for extended window thrombolytics would likely increase provider willingness to treat patients beyond 4.5 hours.


1.           Campbell BCV, Ma H, Ringleb PA, Parsons MW, Churilov L, Bendszus M, et al. Extending thrombolysis to 4.5-9 h and wake-up stroke using perfusion imaging: A systematic review and meta-analysis of individual patient data. Lancet. 2019;394:139-147

2.           Thomalla G, Boutitie F, Ma H, Koga M, Ringleb P, Schwamm LH, et al. Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: Systematic review and meta-analysis of individual patient data. Lancet. 2020;396:1574-1584