Types of Oral Anticoagulation

Vitamin K Antagonists

Warfarin

Warfarin is a type of vitamin K antagonist which acts by working against vitamin K in the liver. Common indications for its use is in stroke prevention in atrial fibrillation (AF), preventing thrombus formation in patients with mechanical heart valves (MHV), and treatment of venous thromboembolism (VTE). Warfarin has been prescribed for over 50 years, it is well understood and there is a large history of experience in its clinical use. The effect of treatment is easy to measure and to monitor compliance with treatment. The widespread use of Warfarin will likely continue among patients who are already stable, have severe renal impairment and for anticoagulant indications for which the newer novel agents have not been evaluated, such as MHV.¹ Reversal can be achieved with Vitamin K and Prothrombin Complex Concentrate (PCC).
 

Direct (or Novel) Oral Anticoagulants (DOAC’s/NOAC’s)

Direct Xa Inhibitor (Rivaroxaban, Apixaban)

Direct Thrombin Inhibitors (Dabigatran)
 

The novel or new oral anticoagulants (NOACs) are a group of drugs recently introduced to Australia (2013) that act as either a direct thrombin inhibitor or a direct inhibitor of Factor Xa. These agents have been shown to provide excellent clinical reduction in thrombosis with an acceptable bleeding profile. All have a simple fixed dosing whether daily or twice daily, and no significant dietary interactions. DOAC’s are at least equivalent to warfarin with respect to prevention of stroke and systemic embolization with some showing statistical superiority. Lower rates of major bleeding were found, with a significant reduction in the rate of intracranial haemorrhage ⁵.  A wide therapeutic window enables fixed dosing in adults without the need for laboratory monitoring.
 

Clopidogrel

• Clopidogrel is an anti-platelet drug that that inhibits the ability of platelets to clump together as part of a blood clot. Clopidogrel prevents blood clots by irreversibly binding to the P2Y12 receptor on platelets, preventing adenosine diphosphate (ADP) from activating platelets. It belongs to a class of drugs called P2Y12 inhibitors. ⁶
   

Ticagrelor

• Ticagrelor is an oral antiplatelet drug, it inhibits platelet aggregation by blocking the platelet P2Y adenosine disphosphate receptor, ticagrelor binds reversibly, so its inhibitory effect on platelet aggregation is more quickly reversed. Ticagrelor is given in combination with aspirin for the treatment of acute coronary syndrome. There is no current reversal agent. ⁷ 

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Half-life and Elimination

DRUG	HALF LIFE	ELIMINATION
Warfarin	35 hours	Hepatically metabolised, renal and faecal excretion
Rivaroxaban	5-9 hours (healthy) 11-13 hours (elderly)	67% renal (half is inactive drug), 33% faecal
Apixaban	8-15 hours	25% renal, 75% faecal
Dabigatran	12-17 hours (prolonged in renal impairment)	80% renal. Diuresis must be maintained to promote adequate drug clearance.
Clopidogrel	6 hours	50% renal, 50% faecal
Ticagrelor	9 hours	Metabolism by CYP-450 enzymes