title: The discovery of dabigatran etexilate for the treatment of venous thrombosis.
abstract: BACKGROUND
  Venous thromboembolism (VTE) can be life-threatening and requires anticoagulant treatment; for many years, vitamin K antagonists, e.g. warfarin, were the only oral anticoagulants available for long-term treatment. Although highly effective, they have many limitations including a slow onset, a multitude of drug-drug and drug-food interactions, and a narrow therapeutic range. These limitations spurred the search for non-vitamin K antagonist oral anticoagulants (NOACs), such as dabigatran etexilate.
  
  
  METHODS
  The authors illustrate the progression of preclinical and clinical studies leading to the development of dabigatran, the only approved NOAC to act by direct thrombin inhibition. They focus on molecule discovery, animal models of thrombosis, clinical trials and post-launch activities in VTE treatment.
  
  
  CONCLUSIONS
  Dabigatran demonstrated comparable efficacy to the highly effective warfarin, and a more favourable safety profile in trials of VTE treatment. A favourable anticoagulant safety profile in addition to efficacy is essential for VTE treatment. Availability of the dabigatran-specific reversal agent, idarucizumab, provides a means of rapidly reversing the anticoagulant effect if required. Future investigations into the optimal duration of VTE treatment and an evaluation of the impact of idarucizumab, in real-world studies, could provide valuable information to help optimise treatment for selected patients.
authors.affiliation: a Department of Clinical Development & Medical Affairs , Boehringer Ingelheim GmbH & Co. KG , Ingelheim am Rhein , Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Feuring
authors.affiliation: a Department of Clinical Development & Medical Affairs , Boehringer Ingelheim GmbH & Co. KG , Ingelheim am Rhein , Germany.
authors.forename: Joanne
authors.initials: J
authors.lastname: van Ryn
mesh_terms: D000284:Administration, Oral; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000925:Anticoagulants / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000931:Antidotes / Q000627:therapeutic use; D000069604:Dabigatran / Q000009:adverse effects / Q000494:pharmacology / Q000633:toxicity*; D004195:Disease Models, Animal; D004347:Drug Interactions; D006801:Humans; D054556:Venous Thromboembolism / Q000188:drug therapy*; D014859:Warfarin / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000925:Anticoagulants; D000931:Antidotes; D014859:Warfarin; C000594745:idarucizumab; D000069604:Dabigatran
keywords: Dabigatran etexilate; deep vein thrombosis; direct thrombin inhibitors; non-vitamin K antagonist oral anticoagulants; pharmacology; prevention; pulmonary embolism; treatment; venous thromboembolism