What is the difference between apixaban, dabigatran, edoxaban and rivaroxaban?❓❓❓

For a long period of time in the past, warfarin was the only oral anticoagulant drug until the emergence of novel oral anticoagulant drugs. Although they are called "novel" oral anticoagulants, they are only relative to warfarin. New oral anticoagulants include factor Xa inhibitors (apixaban, edoxaban, and rivaroxaban) and direct thrombin factor IIa inhibitors (dabigatran). Learn more about these four new oral anticoagulants below.

1. Mechanism of action.

The anticoagulant effect of warfarin is produced through multiple targets. It exerts an anticoagulant effect by inhibiting the hepatic synthesis of vitamin K-dependent coagulation factors II, VII, IX, and X.

Since new oral anticoagulants are anticoagulant drugs that act on a single target, their anticoagulant effects are easier to control. Apixaban, edoxaban, and rivaroxaban exert their anticoagulant effects by inhibiting coagulation factor Xa. Dabigatran exerts its anticoagulant effect by inhibiting coagulation factor IIa.

2. Risk of bleeding.

All of the novel oral anticoagulants were associated with a lower risk of intracranial hemorrhage than warfarin. Additionally, they do not increase the risk of fatal bleeding. Apixaban and edoxaban did not increase the risk of gastrointestinal bleeding compared with warfarin. However, dabigatran and rivaroxaban were associated with an increased risk of gastrointestinal bleeding compared with warfarin.

3. Indications.

a.) The difference between novel oral anticoagulants and warfarin: Atrial fibrillation can be divided into non-valvular atrial fibrillation and valvular atrial fibrillation (moderate to severe mitral stenosis, mechanical valve replacement surgery). Warfarin is recommended for valvular atrial fibrillation. Novel oral anticoagulants are recommended for nonvalvular atrial fibrillation.

b.) Differences between the novel oral anticoagulants:

• Apixaban is generally only used for anticoagulation after hip and knee surgery.
• Edoxaban and dabigatran can be used to prevent stroke in non-valvular atrial fibrillation. They can also be used to prevent deep vein thrombosis.
• Rivaroxaban can be used for more indications. It can be used to prevent non-valvular atrial fibrillation stroke, treat and prevent deep vein thrombosis and pulmonary embolism, anticoagulant therapy after hip and knee replacement, prevent coronary artery disease and peripheral artery disease.

4. Pharmacodynamics and pharmacokinetics.

The difference between novel oral anticoagulants and warfarin:

1. Novel oral anticoagulants reach peak blood concentrations more quickly after taking them, making them more effective. Their short half-life causes patients to lose their anticoagulant effect sooner after discontinuing the drug. It makes novel oral anticoagulants have good dose-response relationships. Activated coagulation factors II, VII, IX, and X are not affected by warfarin. Since the half-life of coagulation factor II is as long as 60 to 72 hours, it takes 2 to 7 days for warfarin to achieve its maximum effect.
2. Novel oral anticoagulants have few drug and food interactions.
3. Novel oral anticoagulants are rarely affected by disease or genetic factors. Patients have good medication compliance with them.
4. Andexanet is the specific reversal agent for apixaban, edoxaban and rivaroxaban. Idarucizumab is the specific reversal agent for dabigatran. If warfarin is overdose, vitamin K can be given intravenously.

5. Dosage of novel oral anticoagulants.

1. Apixaban: It is recommended to be taken at 2.5 mg twice daily. It is not affected by eating.
2. Edoxaban: It is recommended to take 60 mg once daily.
3. Dabigatran: It is recommended to be taken at 150 mg twice daily with meals. Dabigatran may damage the esophagus, so it is generally recommended to take it during or immediately after a meal and drink enough water (more than 100ml). Patients should remain in an upright or sitting position for more than 30 minutes after taking dabigatran.
4. Rivaroxaban: It is recommended to take 10mg once daily with or without food. However, rivaroxaban 15 mg or 20 mg tablets should be taken with food.

The frequency of administration is generally determined based on the half-life of drug efficacy and the half-life of plasma clearance. Patients should fix the time they take their medication every day. Novel oral anticoagulants generally do not require dose adjustment. However, in special circumstances (such as combined medication, the patient is underweight, old, or has liver and kidney problems), the dose may need to be reduced. 

6. How should novel oral anticoagulants replace other anticoagulants? 

Replacement of warfarin with novel oral anticoagulants: Check INR after discontinuing warfarin. Novel oral anticoagulants can be used when INR <2.0.

Substitution between novel oral anticoagulants: Patients should take the new novel oral anticoagulant directly with their next dose. Delayed dosing may be required in patients with renal impairment. 

Replacement of heparins with novel oral anticoagulants: The patient takes novel oral anticoagulants with the next injection of LMWH. The patient can take novel oral anticoagulant directly after stopping UFH.

Replacement of novel oral anticoagulants with injectable anticoagulants: The patient can switch to injectable anticoagulants when taking the next medication. Delayed dosing may be required in patients with renal impairment.

Replacing antiplatelet drugs with novel oral anticoagulants: Patients can take novel oral anticoagulants after they stop taking aspirin or clopidogrel.