DOACs

Question 1

What are DOACs indicated for?

Answer 1

1) Venous thromboembolism
2) Also indicated for primary prevention of VTE in patients undergoing elective hip or knee replacement surgery.
3) Atrial fibrillation (AF): Anticoagulation with DOACs is indicated to prevent stroke and systemic embolism in patients with non-valvular AF who have at least one risk factor (including previous stroke, symptomatic heart failure, diabetes mellitus or hypertension).

Question 2

outline the MoA of DOACs

Answer 2

1) Apixaban, edoxaban and rivaroxaban directly inhibit activated factor X (Xa), preventing conversion of prothrombin to thrombin.
2) Dabigatran directly inhibits thrombin, preventing the conversion of fibrinogen to fibrin. All DOACs therefore inhibit fibrin formation, preventing clot formation or extension in the veins and heart.

Question 3

why are DOACs less effective in arterial circulation?

Answer 3

in the arterial circulation clots are largely platelet driven, and are better prevented by antiplatelet agents

Question 4

Outline some of the adverse effects caused by DOACs

Answer 4

1) Bleeding particularly epistaxis, GI and genitourinary haemorrhage
2) Anaemia
3) GI upset
4) Dizziness
5) Elevated liver enzymes.

Question 5

Discuss the bleeding risk associated with Warfarin compared to DOACs

Answer 5

1) The risk of intracranial haemorrhage and major bleeding is less with DOACs than with warfarin.
2) But, the risk of GI bleeding is greater with DOACs, possibly due to intraluminal drug accumulation causing local anticoagulant effects

Question 6

Who should DOACs be avoided or used in caution with?

Answer 6

1) Avoided in people with active, clinically significant bleeding
2) Risk factors for major bleeding, such as peptic ulceration, cancer, and recent surgery or trauma, particularly of the brain, spine or eye.
3) Dose reduction required in hepatic or renal disease
4) DOACs are contraindicated in pregnancy and breastfeeding, risk of harm to is unknown

Question 7

Outline the important interactions with regards to DOACs

Answer 7

1) Risk of bleeding is increased by concurrent therapy with other antithrombotic agents (e.g. heparin, antiplatelets and NSAIDs).
2) CYP inducers/inhibitors e.g. The anticoagulant effect can be increased by macrolides, protease inhibitors and fluconazole
3) Caution with strong CYP3A4 and P-gp inducers e.g. rifampicin, phenytoin, carbamazepine, phenobarbital or St. John’s Wort as they may lead to reduced rivaroxaban concentrations

Question 8

what is the typical dose of rivaroxaban for the following indications:

1) VTE treatment
2) Prevention of stroke in AF
3) Prevent VTE following hip or knee replacement

Answer 8

1) VTE treatment: 15 mg 12-hrly
2) Prevention of stroke in AF: 20 mg daily (lifelong)
3) Prevent VTE following hip or knee replacement:10 mg daily (14 days)

Question 9

Which DOAC needs to be taken with food?

Answer 9

Rivaroxaban, but not the other DOACs, must be taken with food as this affects its absorption.

Question 10

Patients should contact a healthcare professional immediately if they develop which symptoms while taking NOACs?

Answer 10

1) prolonged or serious bleeding
2) weakness
3) Tiredness or breathlessness that could be signs of anaemia

Question 11

Outline the monitoring requirements for DOACs

Answer 11

DOACs do not require routine monitoring. (Dose adjustment based on CrCl)