Watch the exclusive #ESOC2021 interview between Barbara Casolla and PI Karin Klijn on the APACHE-AF: Apixaban vs Antiplatelet drugs or No Anti-thrombotic Drugs After Anti-coagulation-associated intracerebral hemorrhage in patients with AF Trail.
So good morning everybody my name is barbara cazola from the vascular neurology department of nice in france and i have the honor today of being with professor karen klein who is the chair of the neurology department at rutland university medical center in mimikin the netherlands she is the co-principal investigator of the randomized clinical trial apache af
Which is the acronym for apixaban after anticoagulation associated intracerebral hemorrhage in patients with atrial fibrillation and she collect this random ice clinical trial with professor bart van der hoff from utrecht medical center good morning professor klein it’s a great morning to be with you um so professor klein can you could you please tell us more
About the rationale of apache f travel piece yes thank you very much barbara um patient with atrial fibrillation who are on anticoagulation may experience an interstitial hemorrhage while they are on this medication and we have a long-standing and pressing clinical dilemma whether after the ich should we restart the anticoagulation or avoid anticoagulation as
The best long-term strategy for the prevention of recurrent stroke either interstellar hemorrhage or ischemic stroke and systemic thromboembolism and can you briefly summarize the design and the patient selection of this study yeah we performed a phase two randomized control trial to um really um for the first time have um reliable estimates from a randomized
Comparison of patients who did and who did not restart anticoagulation and and we chose as our treatment arm at pixaband and um we performed this in 16 centers in the netherlands as a phase ii open label clinical trial with blinded outcome assessment and our main inclusion criteria were that the ichs had to have occurred while patients were on anticoagulation
And the timing of that was in the previous 7 to 90 days patients had to have a jets fast score of 2 or larger and a modified ranking score of 4 or smaller and then then we randomized them one two one to a big span five milligrams twice daily or avoiding anticoagulation and in the anticoagulation group the physicians could choose whether or not they wanted to
Start an antiplatelet for example if there was another indication for antiplatelet therapy our primary outcome on purpose was the combination of non-fatal stroke so including both ich and ischemic stroke or vascular death thank you and which were the main difficulties you faced in the recruitment of patients in apache health well we um we had a um a slow
But steady recruitment rate and our main issue was actually we also looked at that and that many patients who have an ich while they are on ant regulation they do not survive so that was the main reason why people could not be included and we had some instances of as well of doctors or patients having a strong opinion about the treatment despite the fact that
There’s no evidence on what is actually best for secondary prevention in this patient group and what were the expected results for apache f professor blind well x factors is always difficult of course we had a hypothesis in the earlier days some years ago people were very reluctant to restart anti-coagulation and i think we were more afraid probably than of ich
Then of recurrent ischemic stroke which resulted in the fact that only a very small percentage of patients are restarted on anti-regulation if you look in the literature around 20 in later years um observational evidence which is of course um confounded um showed that it might be safe and maybe even better to restart anticoagulation but there was no um there was
No real numbers especially not from the time that we now give nomox instead of vitamin k antagonists so our purpose really was to get reliable estimates from a randomized comparison but with the idea that a restarting anti-coagulation might be in the end be beneficial but of course in this phase two study of 100 patients we could not uh have a definite answer
To that question and what did you finally find so well we randomized 101 participants um with the median age of 78 years 28 had lower ich and we followed them for almost two years 1.9 years in total in the median and 222 percent years of follow-up of the 50 participants who were assigned to a pixel ban 13 had a primary outcome and of those assigned to avoid
Anticoagulation 12 or 51 participants had a primary outcome and that resulted in an annual event rate of 12.6 percent for the apixaban group and of 11.9 percent uh in the group that avoided under regulation indicating that um the annual event rates were similar with overlapping confidence intervals and that the event rate was high in both groups irrespective
Of which trait treatment they received thank you and do you think that there that there are any other potentially identifiable risk factors or underlying conditions uh that may be considered uh for the risk benefit balance of the individual level now of course that’s a very important question this is if you look on the group level and we did exploratory um
Subgroup analysis in this study but those are of course not um they can only be hypothesis generating and they cannot give a firm answer due to the small numbers but a very important question always is in patients with lower ich due to cerebral amyloid angiopathy where we know that the risk of ich is higher than in those with non-local icas um should we not um
Refrain from from giving a noah in in this group as for now i think it is an important question but based on the current evidence that we have i think we still need to continue to randomize those patients in those trials that are still ongoing and those are actually five other studies still ongoing addressing this question in a not exactly the same but similar
Design because at the moment we also for this group don’t know what the best secondary preventive treatment is thank you very much and going forward do you think that uh this criteria will be used to stratify the inclusions uh of patients in the next trial uh on anticoagulation in patients with history of interest river hemorrhage and atrial fibrillation i
Think for now we should not um restrict inclusion to specific groups of patients i think we really still don’t know and only by including all patients um with ichs while they are on anti-regulation in the ongoing studies we will be able to reach the numbers that will be needed to look at specific subgroups of patients with specific characteristics to really
Um come to an individualized risk assessment and the numbers of the the trials probably the the combination in the end of the results in an individual patient data meta-analysis shoots alive allow for this reliable subgroup analysis so we can we can in the end know the answers and have more individualized treatments but not at the moment yet thank you very
Much so with the results of the ongoing clinical trial uh do you think that we will be ready for a clinical radiological score to guide uh clinical decisions uh in treating these patients with anticoagulants and with both history of ich and atrial fibrillation yeah i think it’s very important that the ongoing trials continue and that we obtain more evidence
And hopefully when all these trials are finished and all the results are combined we will we will be able to do exactly that and have more personalized guidance for the best secondary preventive treatment in these types of patients thank you very much professor klein and really congratulations from all the vascular community to you and to your team for this
Big achievement and we thank also the organizers for the great opportunity to highlight the importance of this research topic which we built in our routine clinical practice so we can’t wait for the results at the randomized clinical trial session of the ezoc 2021 thank you very much thank you very much
Transcribed from video
ESOC 2021 – APACHE AF By ESO European Stroke Organisation
