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Latest advances in the reversal strategies for direct oral anticoagulants.
Escal, Jean; Lanoiselée, Julien; Poenou, Géraldine; Zufferey, Paul; Laporte, Silvy; Mismetti, Patrick; Delavenne, Xavier.
Affiliation
  • Escal J; Pharmacology and Toxicology Laboratory, INSERM, SAINBIOSE U1059, Saint-Étienne University Hospital, Jean Monnet University, Saint-Etienne, France.
  • Lanoiselée J; Department of Anesthesia and Intensive Care, Saint-Étienne University Hospital, Saint-Etienne, France.
  • Poenou G; Innovation and Pharmacology Clinical Research Unit, INSERM, SAINBIOSE U1059, Saint-Étienne University Hospital, Jean Monnet University, Saint-Etienne, France.
  • Zufferey P; Department of Anesthesia and Intensive Care, Saint-Étienne University Hospital, Saint-Etienne, France.
  • Laporte S; Innovation and Pharmacology Clinical Research Unit, INSERM, SAINBIOSE U1059, Saint-Étienne University Hospital, Jean Monnet University, Saint-Etienne, France.
  • Mismetti P; Vascular and Therapeutic Medicine Department, INSERM, SAINBIOSE U1059, Saint-Étienne University Hospital, Jean Monnet University Saint-Étienne, Saint-Etienne, France.
  • Delavenne X; Pharmacology and Toxicology Laboratory, INSERM, SAINBIOSE U1059, Saint-Étienne University Hospital, Jean Monnet University, Saint-Etienne, France.
Fundam Clin Pharmacol ; 38(4): 674-684, 2024 Aug.
Article in En | MEDLINE | ID: mdl-38350629
ABSTRACT

BACKGROUND:

Since the late 2000s, Europe has granted approval for various thrombotic risk-related uses of direct oral anticoagulants (DOACs). Unlike traditional anticoagulants, DOACs do not necessitate routine coagulation monitoring. Nevertheless, clinical practice often encounters bleeding events associated with these medications, making the need for effective reversal strategies evident.

OBJECTIVES:

The study aims to take stock of current reversal strategies for DOACs, with a particular emphasis on the latest compounds that have been developed or are currently under development.

METHODS:

For obtaining information regarding the ongoing reversal strategies and the compounds under development, we referred to ClinicalTrials website, PubMed, and Google Scholar.

RESULTS:

In 2024, two specific antidotes to DOACs have already received approval when reversal of anticoagulation is needed owing to life-threatening or uncontrolled bleeding idarucizumab that reverses the effects of dabigatran, and andexanet alfa, designed to counteract activated factor X inhibitors such as apixaban and rivaroxaban. Furthermore, ciraparantag, a potential universal reversal agent, is currently in advanced stages of clinical development. Concerns remain regarding the safety of specific reversal agents, especially concerning the risk of thrombosis. Additionally, the cost of these antidotes remains high. Consequently, nonspecific strategies to counteract anticoagulant medications, including activated charcoal, hemodialysis, and concentrates of coagulation factors, still have utility.

CONCLUSION:

With the validation of specific and nonspecific antidotes, DOACs could supplant traditional oral anticoagulants. This progress represents a significant advancement in anticoagulation therapy. However, ongoing research is crucial to address remaining safety concerns of the specific reversion agents of DOACs in clinical practice.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Hemorrhage / Anticoagulants / Antidotes Limits: Humans Language: En Journal: Fundam Clin Pharmacol Journal subject: FARMACOLOGIA Year: 2024 Document type: Article Affiliation country: Francia

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Hemorrhage / Anticoagulants / Antidotes Limits: Humans Language: En Journal: Fundam Clin Pharmacol Journal subject: FARMACOLOGIA Year: 2024 Document type: Article Affiliation country: Francia