10 things you should know about target-specific oral anticoagulants

Here are some stand-out facts and tips about the target-specific oral anticoagulants.  These agents are becoming increasingly popular in the last few years and there are some nuances among them that you’ll find here. 

To review, target-specific oral anticoagulants (TSOACs) includes dabigatran (Pradaxa), rivaroxaban (Xarelto), apixaban (Eliquis), and edoxaban (Savaysa).  They’re given orally with either once or twice daily dosing and you don’t need to (and in fact, can’t) monitor any coagulation labs in the typical clinical setting. 

1)  Each TSOAC is indicated for stroke prevention in nonvalvular atrial fibrillation and the treatment of DVT or PE.  Rivaroxaban and apixaban have extra indications for DVT prophylaxis after hip/knee surgery and extended treatment of DVT or PE.  Dabigatran is also indicated for extended treatment of DVT/PE.

2)  When using dabigatran and edoxaban to treat DVT or PE, you first need to give 5-10 days of a parenteral anticoagulant.  However, rivaroxaban and apixaban can be given right away as monotherapy.

3)  Each TSOAC has some sort of dose adjustment or restriction dependent on renal function.  Edoxaban is the only one that is not recommended for use if the creatinine clearance is too high.

4)  Each TSOAC can be taken with or without food except for rivaroxaban ≥15 mg which needs to be taken with food (Cmax of 20 mg with food is increased 76%).

5)  None of the TSOACs are indicated in patients with mechanical valve replacements.  Dabigatran has been shown to increase thromboembolic events in these patients (reviewed here) but rivaroxaban is currently in the patient recruitment phase of a study of aortic valve replacements.1

6)  Dabigatran needs to be stored in its original bottle and expires 4 months after it is opened.  That means no weekly pillboxes and no partial prescription fills from the pharmacy (only full bottles of 60 capsules).

7)  All TSOACs are considered noninferior to warfarin for prevention of stroke and systemic embolism in nonvalvular atrial fibrillation but dabigatran (150 mg only) and apixaban also demonstrated superiority to warfarin for this outcome.

8)  When switching between TSOACs and warfarin make sure of the following:

         Warfarin to TSOAC

o   The INR threshold when you start the TSOAC is different among the agents

         TSOAC to warfarin

o   The TSOACs can increase the INR so you can’t use that to reliably assess the anticoagulant effect of warfarin (edoxaban recommends checking the INR right before the dose is due to minimize the drug’s influence)

         TSOAC to TSOAC

o   Give the new TSOAC around the time that the next dose of the discontinued agent would have been (these drugs generally have short half-lives so a few hours can be meaningful)

9)  The 2014 AHA/ACC/HRS atrial fibrillation guidelines recommend anticoagulation for nonvalvular atrial fibrillation patients with a CHA₂DS₂-VASc of 2 or greater.2  Warfarin has a higher “level of evidence” than TSOACs for this recommendation.  But if the patient is unable to maintain a therapeutic INR, the TSOACs are recommended.  See a previous post regarding the update to anticoagulation in atrial fibrillation here.

10) If attempting to reverse the TSOACs, vitamin K and plasma are of no benefit.  If needed in an emergency, 4-factor prothrombin complex concentrate (Kcentra) or factor VIII inhibitor bypassing activity (FEIBA) can be used in addition to supportive care.  These agents have been shown to correct some coagulation parameters but their clinical utility is not established.

These tips of course are not exhaustive, so if you have any tips of your own, feel free to add them below.  When you need specific dosing information, be sure to read the prescribing information for the agent you're choosing (Googling "generic name prescribing information" usually brings it to the top of the list).3-6

References:

1.  ClinicalTrials.gov Comparison of Antithrombotic Treatments After Aortic Valve Replacement. Rivaroxaban: A New Antithrombotic Treatment for Patients With Mechanical Prosthetic Aortic Heart Valve.  Available at:  https://clinicaltrials.gov/ct2/show/NCT02128841 Accessed June, 2015.

2.  January CT, Wann L, Alpert JS, et al. 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2014;64(21):2246-2280. 

3.  Pradaxa (R) [package insert].  Boehringer Ingelheim Pharmaceuticals, Inc; 2015.

4.  Xarelto (R) [package insert].  Janssen Pharmaceuticals, Inc; 2013.

5.  Eliquis (R) [package insert].  Bristol-Myers Squibb Company; 2014.

6.  Savaysa (R) [package insert].  Daiichi Sankyo, Inc; 2015.

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