ESOC 2023 | Breakthrough strokes in patients with atrial fibrillation on DOACs

I think it’s a very intriguing and interesting question because we thought we had solved the problem with AF because of the overwhelming efficacy and safety of DOAC drugs as compared to VKA. So they are highly effective in preventing ischemic stroke at a better safety profile as compared to VKA. And now we realize that despite those very good drugs, the patients have a higher rate of residual ischemic stroke risk about 2% per year, which is not at all negligible and makes up a lot of patients that have DOAC therapy at stroke onset. And there has been a transition from VKA to DOAC over the last decades in almost all developed and developing countries. And now we’re facing this increasing dilemma of patients with AF on anticoagulation but suffering ischemic stroke. So the frequency is estimated in those patients who get DOAC to prevent ischemic stroke but did not have an ischemic stroke, it’s roughly 1 or 2% per year. It’s dependent on several factors. We are not really good at identifying the ones that will fail DOAC therapy. Traditionally we have used CHA2DS2-VASc score, for example, to estimate the residual stroke risk. We see that this score is a bit limited in this populations and some other scores like the ABC score considering age, biomarkers such as troponin and NT-proBNP, and history of prior stroke might be a bit better at predicting DOAC failure. And regarding those that suffer ischemic stroke while already on an anticoagulation, this is really a high-risk group so the risk is several times more frequent. So we see a risk of roughly 5 to 10% annually after an ischemic stroke on DOAC. So those are really patients that have an extreme risk. Considering severity, we see that those that are really on anticoagulation at stroke onset have lower severity as compared to AF patients without antithrombotic treatment. This has been confirmed several times. This is also true for VKA in the case that the INR is in the therapeutic range. But it’s also true for DOAC therapy that stroke severity is lower if patient has adequate anticoagulation on board.

I think it’s more like a psychology issue that we want to do something. We want to change from to IIA to XA inhibitors. We want to change from once daily to twice daily just because then we have the feeling that we did something. Well, actually the data just supports continuing any DOAC. So I think we should not go for VKA in case of DOAC failure. We should continue DOAC therapy. Whether it’s the same DOAC or another DOAC, that’s really a matter of taste, I think. I think we see a signal that adding antiplatelets is not really a good idea. Obviously it’s not randomized data, but we see a signal towards harm in several studies, so we shouldn’t add antiplatelets to those patients. Obviously there might be some patients such as intracranial artery stenosis where it might be reasonable to do so, but certainly not for all DOAC the patients, we shouldn’t add antiplatelets because we’re desperate. Just continue any DOAC treatment at the adequate dose. And I think another take home is really to ensure compliance because a third of patients, they have compliance or adherence issues or they have a reduced dose that is not adequate. So we really need to dive into ensuring that the patient had the correct drug. Also, used it correctly. Some drugs you have to take with food. So we really need to give the information to the patient or the caregiver that we have optimal adherence. And we also need to make sure that in those with cognitive deficits et cetera, that they have the adequate support to get their drugs at home regularly.