NOACs, novel oral anticoagulants

 

NOAC	Trade name	Peak level	Action site (4)	Lower ICH rate than Warfarin (5)	antidote	Reversal by Hemodialysis	other
Dabigatran (2010)	Pradaxa 150 mg/cap BID, 75mg BID when CCr< 30 [1]	0.5—2 hrs.	Thrombin (IIa)	yes	Idarucizumab 2.5gm stat and BID. (6)  four factor prothrombin complex concentrate (4F-PCC)	Helpful (10)	Easily GI bleeding
Rivaroxaban	Xarelto 20mg/tab QD. 15mg QD when CCr<50 [1]	2—4 hrs	Xa	yes	andexanet alfa and four factor prothrombin complex concentrate (4F-PCC)(7*, 8)	will not be dialyzable [11]	Easily GI bleeding
Apixaban	Eliquis 5 mg/tab BID, 2.5 mg BID when > 2 risk factors. [Age ≥ 80; Weight ≤ 60; Serum Creatinine ≥ 1.5 mg/dL] [1]	2—4 hrs. (2)	Xa	yes	andexanet alfa and four factor prothrombin complex concentrate (4F-PCC)(7*, 8)	unclear whether dialysis would be useful [11].	Less significant bleeding, Hazard ratio=0.5 (12)
Edoxaban	Lixiana 60 mg/tab QD, 30mg QD when CCr<30 [1]	1—2hrs (3)	Xa	yes	four-factor prothrombin complex concentrate (4F-PCC) at 50 IU/kg (8, 9)	unclear whether edoxaban can be dialyzed [11].	Less significant bleeding, Hazard ratio=0.83 (12)

 

 * N=56, in setting of ICH, hemostatic efficacy occurred in 64.7% of patients receiving andexanet alfa and 54.8% of receiving 4F-PCC. Thirty-day all-cause mortality was 45.2% for 4F-PCC and 30% for andexanet alfa(7).

 GI = gastro-intestinal.

References

 

1.      Hu A, Niu J, Winkelmayer WC. Oral Anticoagulation in Patients With End-Stage Kidney Disease on Dialysis and Atrial Fibrillation. Semin Nephrol. 2018 Nov;38(6):618-628.

2.      https://www.mayocliniclabs.com/test-catalog/Clinical+and+Interpretive/65848

3.      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4608015/

4.      Polzin A, Dannenberg L, Thienel M, Orban M, Wolff G, Hohlfeld T, Zeus T, Kelm M, Petzold T. Noncanonical Effects of Oral Thrombin and Factor Xa Inhibitors in Platelet Activation and Arterial Thrombosis. Thromb Haemost. 2021 Feb;121(2):122-130.

5.      Katsanos AH, Schellinger PD, Köhrmann M, Filippatou A, Gurol ME, Caso V, Paciaroni M, Perren F, Alexandrov AV, Tsivgoulis G. Fatal oral anticoagulant-related intracranial hemorrhage: a systematic review and meta-analysis. Eur J Neurol. 2018 Oct;25(10):1299-1302.

6.      Lindeman E. Målstyrd antidotterapi vid reversering av dabigatran [Goal-directed administration of antidote for reversal of dabigatran anticoagulation]. Lakartidningen. 2017 Dec 5;114:ESF3. Swedish.

7.      Vestal ML, Hodulik K, Mando-Vandrick J, James ML, Ortel TL, Fuller M, Notini M, Friedland M, Welsby IJ. Andexanet alfa and four-factor prothrombin complex concentrate for reversal of apixaban and rivaroxaban in patients diagnosed with intracranial hemorrhage. J Thromb Thrombolysis. 2021 Jun 8. doi: 10.1007/s11239-021-02495-3.

8.      Carpenter E, Singh D, Dietrich E, Gums J. Andexanet alfa for reversal of factor Xa inhibitor-associated anticoagulation. Ther Adv Drug Saf. 2019 Nov 26;10:2042098619888133.

9.      Galbiati G. Successful Cerebral Hemorrhage Control with Prothrombin Complex Concentrate in a Patient on Edoxaban Therapy: A Case Report. J Blood Med. 2020 Jan 30;11:35-38.

 

10.  Awad NI, Brunetti L, Juurlink DN. Enhanced elimination of dabigatran through extracorporeal methods. J Med Toxicol. 2015 Mar;11(1):85-95.

11.  Crowther M, Crowther MA. Antidotes for novel oral anticoagulants: current status and future potential. Arterioscler Thromb Vasc Biol. 2015 Aug;35(8):1736-45.

12.  https://jtp.taiwan-pharma.org.tw/139/013.html

 

 

edited by Yu-Jang Su  Aug, 17, 2021.