ISC 2026 | Safety and efficacy of thrombolysis in patients with underlying markers of CAA: insights from AcT

The ACT trial was a trial published a few years ago that showed the non-inferiority of tenecteplase compared to alteplase in the treatment of acute ischemic stroke. One question that has lingered in the minds of many stroke physicians is how the safety and efficacy of thrombolysis might differ in patients that have underlying markers of cerebral amyloid angiopathy or CAA. This is typically seen on MRI scans as collections of microbleeds or what we call cortical superficial siderosis staining on the cell side of the brain, as well as some white matter disease features like the white matter hyperintensity multi-spot sign and enlarged perivascular spaces in the brain. As I mentioned, all of these features are really seen on MRI. And in most of the world, when we see patients with an acute stroke, we only have a CT scan for them and have to make decisions about their treatment based on the CT scan. So there’s often a worry in that, you know, well, are we missing some important safety signals that may be gleaned from MRIs? And so what we did in the ACT trial is that we had the benefit of having over 400 patients who had received MRI scans at follow-up. And we looked for these types of chronic markers of injury relevant for CAA on the MRI scans. And we classified each of the patients also in accordance with the radiological criteria for CAA, also known as the Boston criteria. We use different versions of the Boston criteria for the same. And what we found is that of all of the different markers that are relevant for CAA, the presence and burden of chronic superficial siderosis was highly predictive of the risk of hemorrhage after thrombolysis, including the severity of hemorrhage, symptomatic hemorrhage, mortality, and also worse functional outcomes. It was by far the most consistent finding in the study. So there were also similar risks observed with the burden of microbleeds that people had. And people who formerly met radiological criteria for probable CAA based on the versions 1.0 and 1.5 of those criteria also were at a higher risk of hemorrhage after thrombolysis. Importantly, patients that met the latest Boston version 2.0 criteria for CAA did not seem at a higher risk and also patients that had the white matter features of CAA like enlarged perivascular spaces or the white matter hyperintensity multi-spot sign were not at increased risk. So in conclusion what this tells us is that if we are treating patients who have some of these more white matter disease features of CAA, I would not worry excessively about thrombolyzing them. But if you know that somebody has a very high burden of chronic superficial siderosis in their brain, that might give you pause and make you have a bit more of a conversation, if possible, with the patient about potential safety risks of thrombolysis that might be a bit higher than the other average people that we thrombolyze. Importantly, the results do not allow us to say anything about whether these patients can benefit from thrombolysis or not because all patients in the ACT trial received some form of thrombolysis. So that’s an important caveat.

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