ISC 2026 | Microcirculation as a therapeutic target in patients undergoing mechanical thrombectomy

Okay, so CHOICE2 is a very nice confirmation of CHOICE1 results and it shows clearly that we should not rely on the angiography results when we are treating patients with mechanical thrombectomy, because angiography has a major limitation, and that is that it does not show what is happening at the level of the microcirculation, which represents a huge proportion of the total amount of similar blood flow. So the concept of the microcirculation as a therapeutic target is something that can change the landscape. It can change the landscape. Because in the future, in the immediate future, I would say, the physicians will have to learn what to do when we perform a thrombectomy and we obtain a fantastic angiographic result and we open up all the vessels, the large vessels that we can show in angiography. Should we perform more sophisticated serial imaging in order to pick up those who might have remaining perfusion problems at a microcirculation level? Or if we are confident enough that the use of thrombolytics in those patients is safe, can we use it in all of them without much delay in time performing imaging and radiating the patient and postponing the initiation of the rescue adjunct therapy? So these questions, I think, are the immediate future in the field. And of course, the thrombolytic, it is not only the only therapeutic strategy that we may have. It’s certainly one of the options and the best option we have based on data. All the things we have rely on two main things. Preclinical studies, which is always a risk when translating what we identify in rats or rodents in rabbits or in pigs when we translate this into humans but thrombolytics we have the human data but we also have quite relevant preclinical data showing other things but because the question is, why the microcirculation is interrupted despite the opening of the large vessel? And the preclinical data on that respect show that there are two main reasons. One is the formation of microthrombi within the microcirculation itself. You don’t need to explain these possibilities as embolisms. When you are removing the large clot, fragments dislodge and go to the distal vessel. This is a classical thing. This can occur, but it is not necessary because what really happens is that when you block the large vessel at the distal vessel, the lack of blood also facilitates a number of molecular events which are mainly triggered by the release of free radicals, oxidative stress happening at the level of the microcirculation that constricts cells that surround capillaries. And when you open the large vessel, since the capillary remains shut, blood does not arrive to the neurons. So you need to also first clean up all the thrombi that might have formed. And that’s why CHOICE has been so successful in showing benefits because you are cleaning up those capillaries obstructed with thrombi. But now you need to address the reason for the constriction of these capillaries. And this is oxidative stress. So the next logical step that I will be defending is the use of antioxidants. And in that respect, we have been working for many years with the administration of uric acid in patients. And we have also succeeded in demonstrating benefits in the SPAN project in a preclinical multi-lab study funded by the NIH showing that uric acid so far is the only drug that has shown benefits, diminished the emphasis, and improves the outcome of animals receiving this drug. So the next step is going into the confirmatory clinical trial that we are expected to start in 2026, hopefully with the funding of the NIH. And I think that would shut and close the circle surrounding the microcirculation as a therapeutic target in patients with mechanical thrombectomy. And this is basically what I will be discussing in my talk.

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