Upstream versus downstream thrombin inhibition

Expert Rev Cardiovasc Ther. 2016 Nov;14(11):1273-1282. doi: 10.1080/14779072.2016.1224179. Epub 2016 Aug 30.

Abstract

For a long time, vitamin K antagonists (VKA) have been the preferred drugs for the anticoagulation management of both atrial fibrillation and venous thromboembolism. Hereby, the major purpose is to attenuate the onset of thrombosis without affecting hemostasis. Areas covered: Nowadays, non-vitamin K anticoagulants (NOAC), a new class of oral anticoagulants is available for the above-mentioned indications. NOAC are at least as effective and safer with regard to intracranial bleedings compared to VKA, but major bleedings still occur. For this reason, the search for safer anticoagulants is still ongoing. Expert commentary: There are several unmet needs in NOAC management, including selection of optimal drug and dose, uncertainty on specific conditions and lack of drug persistence. There remains to be an important need for safer anticoagulants; 'upstream' anticoagulants including inhibitors of factor XIa may provide additional benefit related to fewer bleeding complications.

Keywords: Anticoagulation; factor XI; factor XII; non-vitamin K antagonist oral anticoagulants (NOACs); vitamin K antagonists (VKA).

Publication types

  • Review

MeSH terms

  • Administration, Oral
  • Anticoagulants / adverse effects
  • Anticoagulants / pharmacology*
  • Anticoagulants / therapeutic use
  • Antithrombins / adverse effects
  • Antithrombins / pharmacology
  • Antithrombins / therapeutic use
  • Blood Coagulation / drug effects
  • Blood Coagulation / physiology
  • Blood Coagulation Factors / antagonists & inhibitors*
  • Fibrinolytic Agents / adverse effects
  • Fibrinolytic Agents / pharmacology
  • Fibrinolytic Agents / therapeutic use
  • Humans
  • Thrombin / antagonists & inhibitors*
  • Thrombin / physiology
  • Vitamin K / adverse effects
  • Vitamin K / antagonists & inhibitors
  • Warfarin / adverse effects
  • Warfarin / pharmacology

Substances

  • Anticoagulants
  • Antithrombins
  • Blood Coagulation Factors
  • Fibrinolytic Agents
  • Vitamin K
  • Warfarin
  • Thrombin