New Direct Oral Anticoagulants (DOACs)

Anticoagulants are used to treat and prevent stroke in patients with atrial fibrillation and venous thromboembolism after orthopedic procedures.

Vitamin K antagonist, such as warfarin, was the anticoagulant of choice for many years. Treatment with vitamin K antagonists require frequent blood tests monitoring, dose changes according to the INR values (International Normalised Ratio), and numerous drug-drug and drug-food interactions.

After more than 60 years, the introduction of a new class of direct oral anticoagulants (DOACs) is a major advance in anticoagulation therapy. DOACs are more safe, convenient and effective alternatives to warfarin. They are also termed as NOACs: Non vitamin-K Oral Anticoagulants. In contrast to warfarin, DOACs show rapid onset of action, rapid offset of action, predictable pharmacokinetics and pharmacodynamics, short half-life, wide therapeutic window, few drug-drug and drug-food interactions, and no need for laboratory monitoring.

DOACs are small molecules that selectively inhibit specific coagulation factors in the blood coagulation pathway. Examples of DOACs include:

• Direct inhibitor of thrombin- Dabigatran etexilate (Pradaxa).It is usually administered once or twice daily depending on indication. Dabigatran inhibits both free and fibrin-bound thrombin.
• Direct inhibitor of factor Xa- These DOACs bind to the active site of factor Xa and block its interaction with prothrombin. A number of factor Xa inhibitors are in clinical development, but following are currently approved for clinical use. Examples of these medication include:
  • Rivaroxaban (Xarelto, Janssen)
  • Apixaban (Eliquis, Bristol Myers Squibb)
  • Edoxaban (Savaysa, Daiichi Sankyo)
  • Betrixaban (Bevyxxa, Portola Pharmaceuticals).

With the introduction of the DOACs, the prescribing practice of physicians has changed progressively. DOACs represent the majority of new prescriptions for anticoagulants, especially when prescribed by cardiologists for patients with atrial fibrillation. Besides ease of management, the major benefit of DOACs is their improved safety without loss of efficacy, and is especially true for the incidence of intracranial haemorrhage. This is an important advantage because bleeding into the brain is the most feared complication of anticoagulation therapy. 

One thing to note is that missing a dose or two of a short-acting DOACs returns the coagulation cascade to near normal which places the patient at risk for thromboembolism. In comparison, missing a dose or two of warfarin simply lowers the degree of anticoagulation and would rarely return the patient to normal.