Topic Discussion: Novel anticoagulants in CKD and ESRD

New Oral Anticoagulants(NOACs)	Renal clearance of parent drug	Dosage in ESRD	GFR 15-29ml/min	GFR 30-40ml/min	GFR >-50ml/min	Dialyzable (yes/no)	Reversal agent
Dabigatran( Direct thrombin inhibitor)	80%	Avoid	75mg BID	150mg BID	150mg BID	Yes with 10% rebound rate	Idarucizumab Dialysis
Rivaroxaban(Factor Xa inhibitor)	36%	15mg QD	15mg QD	15mg QD	20mg QD	No	4-factor prothrombin complex concentrate Andexanet Alfa
Apixaban( Factor Xa inhibitor)	27%	5mg BID	2.5mg BID	5mg BID	5mg BID	No	4-factor prothrombin complex concentrate Andexanet Alfa
Edoxaban (Factor Xa inhibitor)	50%	30mg QD	30mg QD	30mg QD	60mg QD	No	4-factor prothrombin complex concentrate Andexanet Alfa

Patients with atrial fibrillations are being treated with NOACs as they are simple to use, no monitoring and excellent safety profile. They are higher in costs and experience still limited. NOAC use in patients with advanced CKD and on dialysis is substantial and increasing, despite AHA, ACC, and HRS and European Heart Rhythm Association guidelines that endorse warfarin as the anticoagulant of choice when CrCl is <30 ml/min. There are few randomized trial data on NOACs among patients with advanced CKD or on dialysis. Most NOACS are dependent on the kidney for elimination. Since most patients with advanced CKD were excluded in clinical trials, this topic is important. 

The above table summarizes what the current data exists on this topic for use of NOACs in CKD patients with Atrial Fibrillation for prevention of stroke.  Bleeding risk is important in patients with CKD and ESRD due to uremic dysfunction of platelets and use of heparin in HD.  Unfortunately, no patients with CKD Stage V or ESRD were not allowed in any of the NOAC trials. Apixaban was the most commonly used NOAC in a recent analysis in advanced CKD patients. Apixaban and Rivaroxaban have renal eliminations around 30% hence most safe in late stage CKD with lower dosing. Dabigatran and Edoxaban ar 80% and 50% renal elimination respectively and should technically avoided in late CKD patients.  Dabigatran is the only NOAC removed by dialysis based on studies thus far.

This review in JACC summarizes the latest uptodate information on use of these agents in CKD and ESRD patients. – A must read!