Direct Oral Anti Coagulants

Question 1

What are DOACs?

Answer 1

Group of anticoagulants that work by inhibiting Thrombin or Factor X
Dabigatran = Thrombin Inhibitor
Apixaban, Rivaroxaban and Edoxaban are Factor X inhibitors

Question 2

What do NICE say about the use of DOACs in VTE?

Answer 2

DOACs are NOT currently included in the guidelines for VTE treatment because they are novel therapeutics.
They are however included in technical appraisals meaning it is likely they will be included in guidelines soon.
Many trusts and healthcare providers do still use DOACs for VTE regardless of the lack of guidelines as they are shown to be effective and more convenient for patients.

Question 3

What is the Evidence for Dabigatran?

Answer 3

RE-COVER Trial, 2009:
RCT of Dabigatran vs LMWH/Warfarin
-2000 patients *Both groups used parenteral LMWH for 5 days

Both groups had similar values for recurrence and bleeding so Dabigatran was non-inferior to standard

Question 4

What is the evidence for Apixaban?

Answer 4

AMPLIFY Trial, 2013:

• RCT of Apixaban vs LMWH/Warfarin
• 4000 patients *No parenteral anticoagulation in the DOAC group

Both groups had similar recurrence values but Apixaban showed lower incidence of bleeding

Question 5

What is the evidence for Rivaroxaban?

Answer 5

EINSTEIN Trial, 2010:
RCT of rivaroxaban vs LMWH/Warfarin
-3000 patients *No parenteral anticoagulation in the DOAC group

Both groups showed similar recurrence and bleeding rates

Question 6

What is the evidence for Edoxaban?

Answer 6

HOKUSAI-VTE Trial, 2013:

• RCT of Edoxaban vs LMWH/Warfarin
• 8000 patients *Both groups used parenteral anticoagulation

Both groups showed similar recurrence and bleeding rates

Question 7

Which DOAC is better?

Answer 7

NMA-1 Meta Analysis

• Compared the 4 DOACs
• Showed that all 4 had similar recurrence rates
• Apixaban had the lowest bleeding rates
• Dabigatran and Edoxaban less useful because of their need for parenteral anticoagulation (trialled with it so must be used in practice)
• So apixaban is shown to be the most effective for use in ambulatory care of VTE

Question 8

Are DOACs cost-effective?

Answer 8

• 6 months of treatment with Apixaban is shown to be £2400 more expensive than LMWH/warfarin
• however it is a better use of resources e.g doesn’t need continual blood tests and doesn’t require parenteral treatment in hospital with LMWH

Question 9

What are the contraindications for DOAC use?

Answer 9

• Reduced renal function
• Metallic heart valves
• VTE with active cancer
• Pregnancy
• Obesity >120kg
• liver disease
• bleeding risk (lack of reversal agent)