Use of Anticoagulants to Prevent Stroke in Nonvalvular Atrial Fibrillation - Episode 5

Reversal Agents for Direct Oral Anticoagulants

Rajat Deo, MD, assistant professor of medicine at the University of Pennsylvania

Overall, we have seen an increase in the use of dabigatran after the availability of idarucizumab. We should recognize, however, that we know that all 4 DOACs (direct oral anticoagulants) are effective and safe. And from a clinical standpoint, we also recognize that although having a reversal agent may provide comfort, especially to our colleagues in the emergency room or in the trauma stations, their overall use will be quite low.

Praxbind, the reversal agent for Pradaxa (dabigatran), is effective. It acts quickly in terms of halting the anticoagulant effects of dabigatran or the direct thrombin inhibitor, and it’s also very specific for dabigatran. I don’t have any personal experience using the drug, but I’ve reviewed significant clinical data and understand that it is used in high-risk populations at times of significant bleeding and it is effective at reversing the bleeding.

When I speak to my patients about the options for various DOAC therapies, I do indicate that some of the agents have a reversible agent and some don’t—not yet at least. Patients who are concerned about bleeding risks, who are concerned about side effects from intracranial bleeding or gastrointestinal bleeding, often find comfort in being on an oral anticoagulant that has a reversal agent available. In those situations, I will oftentimes prescribe the anticoagulant where reversibility is available. The availability of other reversal agents will provide greater confidence to our patients that they will be on a DOAC; they will be on an oral anticoagulant, where a reversal agent will be available in case they ever need it.

When we make a decision for a particular NOAC (novel anticoagulant) therapy, we are confident that the agent will be effective and safe. The safety data, now, for these agents is based not just on the clinical trials, but it’s also based on the large amount of postobservational data that has come out in the phase IV studies.

Certainly, the availability of a reversal agent is important and it can be important in certain life-threatening situations. This is why, when I have the decision about which oral anticoagulant to prescribe a certain patient, I always mention the availability of the reversal agent, especially for a drug like dabigatran. At the end of day, I just want the patient to be maximally comfortable with the agent. Oftentimes, there are concerns and questions related to potential bleeding effects and other potential side effects, and I believe that by providing them the assurance that a reversal agent is available, that oftentimes convinces them to continue an anticoagulant medication.

Our atrial fibrillation patient population is generally a group of individuals that are elderly and are at risk for other cardiovascular comorbidities. Oftentimes, these are patients that require other cardiac procedures, whether it’s ablation procedures or cardio catheterization for stent placement.

In individuals who are taking a DOAC, it would be ideal to have available an in-hospital reversal agent. We recognize that these procedures can be complicated by cardiac preparation or other bleeding complications, and as a result, the availability of a reversal agent can be very important in those situations.

We appreciate how best to prophylactically treat our atrial fibrillation patients that are at a high risk of systemic embolization or ischemic stroke. We understand the importance of anticoagulation therapy. However, moving forward, I think we have a few challenges.

First, we need to ensure medication compliance and adherence in our populations. We need to emphasize to caregivers across the country that it is important to maintain anticoagulation in these individuals. At the same time, we also need to emphasize to our patients the importance of anticoagulation use.

In addition, we need to start identifying those individuals that do not have clinically overt atrial fibrillation but are still at risk for developing ischemic stroke. Ischemic stroke may oftentimes be the first manifestation of clinical atrial fibrillation. Identifying those individuals before they have their first clinically severe event that can result in significant disability or even death, I think, is important so that we initiate anticoagulation therapy as early as possible.