WSC 2022 | How is oral anticoagulant-associated intracerebral hemorrhage currently managed?
Hanne Christensen, MD, PhD, MSci, University of Copenhagen, Copenhagen, Denmark, discusses the burden of oral anticoagulant (OAC)-associated intracerebral hemorrhage (ICH) and how these patients should be managed. Dr Christensen notes that large proportions of patients admitted with an acute ICH are actively receiving antithrombotic therapy. While large-scale estimates are lacking, Dr Christensen believes that around half of all patients treated for an ICH in her practice are on an antiplatelet, with another quarter taking an anticoagulant. Given the high rates of hematoma expansion seen in the OAC-ICH population, the main goals of acute treatment are to stabilize blood pressure and reverse the effects of the OAC. For patients receiving warfarin, clinical trial data supports the use of prothrombin complex concentrates (PCC) versus fresh frozen plasma for reversal, although more data is needed regarding the impact on patient outcomes. There is no robust, randomized data assessing the efficacy of PCCs in patients treated with direct oral anticoagulants (DOACs). Idarucizumab is a humanized monoclonal antibody, shown to rapidly and durably reverse anticoagulation in patients with intracranial bleeding on dabigatran. For factor Xa inhibitor reversal, andexanet alfa is currently under investigation. While the European Stroke Organization’s recommendation for the use of idarucizumab in patients on dabigatran is strong, a lack of data in ICH means the recommendation of andexanet alfa in patients on rivaroxaban or apixaban is weak. This interview took place at the World Stroke Congress 2022 in Singapore.
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Transcript (edited for clarity)
I think it is in general unestimated how many of the people admitted with an acute ICH who are actually on an antithrombotic being OAC or being an antiplatelet. If I look at the area where I’m practicing myself, about a quarter of the people admitted are on an OAC, and then almost half on an antiplatelet. So basically, it’s majority of the people we’re talking about.
Looking at it, there are more factors in it...
I think it is in general unestimated how many of the people admitted with an acute ICH who are actually on an antithrombotic being OAC or being an antiplatelet. If I look at the area where I’m practicing myself, about a quarter of the people admitted are on an OAC, and then almost half on an antiplatelet. So basically, it’s majority of the people we’re talking about.
Looking at it, there are more factors in it. This is about predicting who will get it. Basically, our ability to predict this is pretty low. The existing score was based on people on warfarin, and the few data we have where we look at present cohorts, the HAS-BLED scale is not really strong in predicting who will get ICH. So that is certainly an area where there’s an unmet need.
If we look at the acute treatment, which I will be covering, the problem is that people with OAC-related ICH, they much more frequently have hematoma expansion. This means that the bleeding extends after the patient has been admitted to hospital. And the idea in the treatment is that we want to reduce this hematoma expansion. That is basically the idea of many of the trials in ICH overall. But in our population, the bleeding expansion, the hematoma expansion, is much more frequent. So what we want to do in stopping the bleeding is mainly two treatment targets.
One is to keep the blood pressure stable, and that is basically the same as with all patients with ICH. The other thing is that we want to reverse the effects of the OAC. And as to warfarin, we have data from one randomized controlled trial showing that PCC is by far superior to fresh frozen plasma in reversing. We do not have data on how this really affects patient outcomes because the trial was too small to give that kind of data, but the trend was that this improved outcomes.
Then when we get to the more novel so-called DOACs and NOACs, we have the direct thrombin inhibitor, dabigatran, that is a specific antidote that has been well implemented in idarucizumab. And we have some experience with that. When we get to the factor Xa inhibitors, there’s also a marketed inhibitor andexanet alpha, but we have less data in people with OAC ICH, and it has not been generally implemented, also because it is extremely costly which has risen some doubts. The combination of not too much data and the costliness has arisen some moderate use of this worldwide.
But a very nice trial is ongoing at the moment, a randomized controlled trial in ICH. So hopefully based on the results from the ANNEXA-I, which will be terminated in about 18 months or something like that, we will be much wiser on this. And we’re not using andexanet alpha. People are using also PCC, but that is only based on theory and the efficacy in healthy subjects to reverse the effects of factor Xa inhibitors, so this is very weak evidence.
So this is basically what we’re doing. So this is an area with a lot of patients and a lot of low level evidence.
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Disclosures
Hanne Christensen is national lead for the ANNEXA-i trial and has received speaker’s honoraria from BMS and Bayer.
