ESOC 2026 | Early findings from a study on breakthrough stroke in patients on DOACs with AF

I would like to talk a little bit about our early findings from our study. So our study is called ischemic stroke despite primary preventive oral anticoagulation in atrial fibrillation, a national registry study. And I would first like to say many thanks to my wonderful supervisors, Boris Keselman, and my main supervisor, Michael Mazya, for all of their help throughout this period. So first thing we have to talk about is what is a breakthrough stroke. So in a patient that has atrial fibrillation and is currently treated with anticoagulation in the form of DOAC, direct oral anticoagulant. If they, despite this treatment, suffer a new ischemic stroke, that is what we are referring to as a breakthrough stroke. And there have been several studies on this topic since 2020 and forward. But so far, none of these studies have shown any superior DOAC to DOAC switching strategy. So that was what we wanted to explore a little bit in our study as well. So a little bit about the background. Even though you treat atrial fibrillation with one of the oral anticoagulants, there is still a risk of a breakthrough stroke each year. So the risk is around 3.75% a year in a meta-analysis that was presented in 2025. But what was interesting was that they also could see that if you have already suffered one breakthrough, then the risk for further breakthrough strokes is 7.20% per year. And these risks are actually a little bit higher than what we expected from previous RCTs. And what is the different possible mechanism for a breakthrough stroke? You have to consider that it may be because of a different etiology, like atherosclerosis of the neck vessels or intracranial vessels, small vessel disease, or any coagulopathy. In the study by Polymeris et al., they looked into this and they could see that competing mechanisms accounted for approximately 24%. It may also be because of insufficient anticoagulation, typically if the patient is prescribed too low a dose of DOAC or if they have had an interruption of the treatment because of a minor surgery or low compliance. That accounts for approximately 32%. But even despite this, there is, in the Polymeris study, they could see that true cardioembolism, despite sufficient anticoagulation, accounted for 44%. And as I mentioned so far, there have been some studies on this field. Last year, Romoli et al. made a meta-analysis of eight of the most cited studies. And to conclude, they could not find that switching from one DOAC to another DOAC was better than keeping the same DOAC. They did find, however, that switching from a DOAC to vitamin K antagonist was inferior and increased the risk of an ischemic stroke recurrence and for an intracerebral hemorrhage.

So the current guidelines, 2024 ESC guidelines for the management of atrial fibrillation, they actually suggest that if you have a stroke breakthrough on oral anticoagulation in atrial fibrillation, you should do a thorough diagnostic workup to exclude competing causes. You should also look over the dosage and the adherence. And they do not recommend adding antiplatelet treatment on top of DOAC if you don’t have any specific reason for doing so. And they do not recommend switching either between the DOACs or from DOAC to VKA if you don’t have any specific reason.

So our study, we wanted to look at this field in the Swedish stroke population. We have a very nice national stroke register called Riksstroke, validated and with excellent coverage. So we took all of the patients that had suffered a breakthrough stroke from 2016 until 2023. And we took those patients from the register, we found a total of 4,466 patients, and we divided them into four different groups, according to what further anticoagulation strategy that you chose. So the first group that was the people that kept the same DOAC, there was no switching. Second group was the people that switched from DOAC to a different DOAC within the factor Xa group. There are currently three different medications available within this group. Third group was the people that switched DOAC to a DOAC with a different mechanism of action. There are also one DOAC that is a direct thrombin inhibitor. So you could switch between factor Xa and the direct thrombin inhibitor or vice versa. And the fourth group was the group that switched from DOAC to VKA, vitamin K antagonists. So we took those four groups and we followed them for 90 days, plus minus 15 days and performed a multivariate logistic regression and did some adjusting for age, sex, treating hospital, common stroke risk factors, and stroke severity.

And our findings are quite actually in line with the findings found in the meta-analysis from last year, we could not find any superior DOAC to DOAC switching strategy compared to keeping the same DOAC. But we did find, similarly as the meta-analysis from last year, we did find that switching from DOAC to VKA, vitamin K antagonist, increased the risk of our primary outcome, which was the composite of any stroke and all-cause mortality within this time period. And it also increased the risk of all-cause mortality taken separately.

So our strengths of this study, we would say, is that we were able to gather a large amount of patients, one of the largest in this field so far. And the quality of the data is very good. We have a very good validated register, as I told you. So that’s very nice. And also we chose to be one of the first studies to look at patients suffering a breakthrough that hasn’t previously had any documented cases of ischemic stroke or TIA. So this was an attempt to look at patients from this first group that I talked about that has the lower risk per year of a breakthrough. So an attempt to look at patients that has this treatment as a primary preventive.

The weaknesses though of this study, we cannot say if these patients really did have the correct DOAC doses. We cannot say if they had any interruptions of treatments and we cannot say anything about compliance. We did see that, when we looked at the sizes of these four groups, the group where the patients kept the same DOAC accounted for approximately 89% of these patients. And we do think that within this group, there may be a lot of patients where there were interruptions of treatment or compliance issues. It’s also unclear if our patients had any competing mechanisms because that we cannot say from the register. And also the group where you choose to switch from DOAC to VKA that may have actually been indications for this switch, such as mechanical heart valves or antiphospholipid syndrome.

So next steps, this was the early results. Now we have gathered long-term data for each patient as well. And next step will be to do a multivariate COX regression for the entire research period. So then we will have years of follow-up data to see if these results hold true over the years. And also very interesting, the patients that were excluded so far, the ones that have had documented breakthrough stroke already, those we will study in an additional study to look at those patients and see do they differ from this cohort.

This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.