International Stroke Conference
Philip Chang, MD
This year’s International Stroke Conference revealed big advances and changes to the acute ischemic stroke guidelines. I had a great time at the Los Angeles Convention Center and learned a lot, as new exciting trials revolutionized the acute ischemic stroke treatment landscape, most notably tripling the reperfusion time windows. As with every conference, there were tons of different lectures and abstracts to go to, but I’ll highlight what I found the most interesting, and key take-home points from the conference.
Day 1 Highlights: Tripling the Endovascular Time Window
DEFUSE 3: Key Take-Home Points:
- Bottom Line: DEFUSE 3 patients with a large vessel occlusion and a perfusion mismatch of at least 70mL on CT or MRI perfusion scans were overall 3 times more likely to obtain functional independence if they received thrombectomy within 6-16 hours from their last known well.
- Key Results: The benefit of clinical outcome via ordinal shift on the mRS or having functional independence (mRS 0-2) was seen in many subgroups. Benefit was preserved in all subgroups, whether patients were selected using CT vs. MRI, whether they were older or younger patients, whether they had an unknown onset time or witnessed onset, as well as those randomized over and under 11 hours. In addition, there was no difference in symptomatic ICH, and even a benefit in mortality (14% vs. 26%) in favor of thrombectomy for those who had thrombectomy later than 11 hours. This was an interesting finding as patients under 11 hours did not have a mortality benefit. Perhaps those patients who still had a penumbra at 11 hours had very strong collaterals, as the benefit was mainly from worse outcomes in the medical group. Benefit was seen in the DEFUSE 3 patients that would have met selection criteria for DAWN, as well as those who did not meet selection criteria for DAWN.
- Point to Ponder: How would we translate this result back in our home institutions? The revised AHA guidelines did not give a clear guidance on how to select patients for the extended thrombectomy window. The recommendation was to select patients that met either DAWN or DEFUSE 3 criteria should be considered for thrombectomy as a Class IA recommendation. But which modality would be most appropriate? There are clear differences in inclusion criteria for both studies, and it seems impractical for an institution to have 2 different screening policies for similar patient populations. Some key questions institutions likely had going home:
- Do we use CT or MRI perfusion scans? It seems that the easiest way to go would be to pick CT perfusion as a first-line scanning as patients would already be in the CT scanner, which is readily available in most EDs, and only software programming would be needed for automated perfusion mapping. In addition, MRIs tend to take up to 40 minutes or more to complete and are full of possible contraindications for use, especially if a patient is unknown to the treatment center. In addition, many community centers do not have MRI available 24 hours a day.
- What protocol do we use for patient selection: NIHSS vs. CTP-CBF (DAWN) or CTP-CBF vs. CTP-TTP (DEFUSE 3)? The idea that the AHA guidelines had was to include as many patients as possible. It seems that the easiest way to go about doing this would be to have a serial screening method.
- Patients with acute stroke in last 24 hours get an NIHSS and CT Perfusion/Angiography showing a large vessel occlusion:
- Select for DAWN:
- Age: Over or under 80?
- Is their NIHSS>10 or >20?
- Core Infarct: Is the CTP-CBF<30% <21mm, 31mm, or 41mm?
- If DAWN Eligible, thrombectomy.
- If DAWN ineligible, is the patient’s last normal under 16 hours?
- Is NIHSS>6?
- Is there an imaging perfusion mismatch >70mL?
- If yes to both, then thrombectomy.
- In this way, we can select for all the DAWN-eligible patients within 16-24 hour window, and all the patients eligible for either DAWN or DEFUSE 3 in the 6-16 hour window.
EXTEND-IA-TNK: Key Take-Home Points:
- Key Take-Home Point: In tPA-eligible patients who are also candidates for thrombectomy, tenectaplase is at least as good as, if not better, than alteplase.
- Rationale: Tenectaplase is an extremely popular thrombolytic in the cardiac world, having seen much more use these days compared to the other thrombolytics for acute coronary reperfusion. Compared to alteplase, our only FDA-approved drug for the treatment of acute stroke, tenectaplase is a genetically modified tPA that has higher fibrin binding specificity and biological half-life than alteplase. Theoretically, the higher fibrin binding specificity should make it a targeted thrombolytic for acute clots and reduce spontaneous bleeding elsewhere. The longer biological half-life allows tenecteplase to be a one-time IV injection rather than the 1-hour infusion of tPA, which may lead to quicker thrombectomy times.
- Key Findings: They enrolled 204 patients within 4.5 hours who were tPA and thrombectomy eligible with the outcomes of mTICI at initial angiography, 24 hour NIHSS, and 90-day mRS. TNK was found to be superior for having an initial angio of TICI2b/3 at initial angiography (22% vs. 10%, p-0.02). TNK was also found to be superior at 90-day ordinal mRS shift (OR 1.7, p=0.037). There was a trend towards functional independence (p=0.06) and mortality (10% vs. 18%, p=0.08) for the TNK group. There were no differences in symptomatic ICH (1% each group).
- What this means: We may potentially have a more effective thrombolytic that joins the ranks of alteplase for acute stroke treatment. Tenectaplase has been shown to be at least as good if not better than alteplase as thrombolytic treatment for endovascular patients. This is very promising and exciting as a single-bolus push can improve quality in things such as transfer times to hospitals if the initial center is not thrombectomy capable. I am eagerly awaiting further studies to see if tenectaplase is also acceptable to use in non-endovascular patients.