Non-anti-vitamin k anticoagulants: lights and shadows
I would like to share with you a summary of this week’s post regarding the bleeding effects of oral anticoagulants and how g-Nomic® pharmacogenetics interpretation software can help in the day-to-day medical practice.
In several previous blogs we have highlighted the importance of initial dose adjustment for warfarin treatment applying pharmacogenetics criteria, as noted in the drug label since 2011.
Since 2010 we have available on the market the non-anti-vitamin k anticoagulants: dabigatran (Pradaxa®), rivaroxaban (Xarelto®), apixaban (Eliquis®) and edoxaban (Lixiana®). Since 2013 there are guidelines for their prescription, and there was an update earlier 2018: The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation.
What is the consequence of not following the recommendations, when these drugs are prescribed? More bleeding than expected and also more thrombosis.
A review on this topic has just been published, based on 220 publications related to 117 different comparative studies: Interventions for Preventing Thromboembolic Events in Patients with Atrial Fibrillation: A Systematic Review.
Where is the problem? These new non anti-vitamin k anticoagulants are usually prescribed stating that "there is no need for control analysis" and the reality is that so far there are no tests to monitor the anticoagulant status. Making guidelines even more important to follow. And, what are the fundamental points of the guidelines? Interactions with other medications.
The guidelines provide a list of the most frequently used medication in cardiology, which interacts with these new anticoagulants. They also state that certain drugs should not be prescribed together. And depending on the cases, decrease the dose of the anticoagulant.
The question is: Are all the possible drugs that interfere listed in these guidelines? The answer is No, only the more frequently used in cardiology.
It is written in the guidelines and drug labels of the four anticoagulants "Strong dual inhibitors of CYP3A4 and P-gp increase blood levels of the drug: Reduce dose to 2.5 mg or avoid concomitant use. Simultaneous use of strong inducers of CYP3A4 and P-gp reduces blood levels of the drug: Avoid concomitant use.”
The question is: Do all clinicians know which drugs are inducers and inhibitors of CYP3A4 and P-gp? Or, can they have them in mind before prescribing? Or, how can they know?
Finally, we should not forget the patient's genetics, especially the ABCB1 gene that encodes the transport protein P-gp, which determines the plasma levels of anticoagulants, according to the phenotype of each person.