Page 578 - fbkCardioDiabetes_2017

554 Novel Oral Anti Coagulants In Chronic Kidney Disease

cleared by standard 4 hour hemodialysis (dialysate The 2015 updated European Heart Rhythm Associ-
flow rate 500ml/min, blood flow rate 350 to 500 ml/ ation practical guidelines on the use of non-vitamin
min, no heparin)[2]. Hence in patients on apixaban K antagonist anticoagulant agents in patients with
with life threatening bleeding or drug overdose, dial- nonvalvular AF recommend refraining from NOACs
ysis is not effective to remove apixaban from circu- use in dialysis patients and those with CrCl <30ml/
lation. Although 4- factor prothrombin complex con- min[2,5] (Table 1 & 2)
centrate may reverse the effect of apixaban.
Bullets:
Edoxaban , a newer factor Xa inhibitor approved for
anticoagulation use in the United States of America • Warfarin can be used in all stages of CKD includ-
although it’s not marketed in the US at present.[2] ing those patients on dialysis
Renal clearance is about 50% of the un-metabolized • Concomintent use with anti platelet therapy exer-
drug. Because of an increased risk of ischemic stroke cise extreme caution while using warfarin.
compared to warfarin observed in the registered tri-
als, the FDA has now contraindicated the use edox- • Persistent use of warfarin may produce a contition
aban in individuals with super normal renal function. called warfarin nephropathy with decrease in GFR.
The American College of Cardiology and the Ameri- • NOACs such as dabigatran, apixaban, edoxaban
can Heart Association(AHA-ACC ) and Heart Rhythm and rivaroxaban require dose adjustment in vari-
Society (HRS) guildelines indicate warfarin as gold ous stages of CKD and requires long term study
standard therapy in stage 4(eGFR between 15 and 30 for their safety in CKD.
ml/min/m2), stage 5CKD(eGFR <15ml/min/1.73m2) • Apixaban has been approved by FDA for use in
and patients on dialysis due to various degree of re- Hemodialysis patients
nal clearance of all NOACs [2].

Parameters Warfarin Apixaban Rivaroxaban Edoxaban Dabigatran
Renal clearance <1% 27% 35% 50% 80%
Dosing recommen- Varying dosage Serum creatinine≥1.5mg/dL,- CrCl≥50mL/min, Crcl≥50mL/min, CrCl≥50mL/min, no
dation no adjustment(i.e 5mg BID) a* no adjustment no adjustment adjustments (i.e 150
(i.e 60mg OD) b* mg BID)*
(i.e 20 mg OD)*

Dosing if CKD 20% lower CrCl 15-29mL/min: 2.5 mg 15mg OD when 30mg OD when CrCl<50ml/min/m 2
dosage? BID CrCl CrCl 15-49 mL/
min* 110mg twice daily *
If two-out-of-three: age≥- 15-49mL/min*
80years,weight ≤60kg,
serum creatinine≥1.5mg/dL*
Not recommended if Can be used in <15mL/min** <15mL/min <15mL/min 30mL/min
ESRD and on
RRT
Reversal agent Vitamin K,FFP, 4F-PCC 4F-PCC 4F-PCC Idarucizumab
4F-PCC
Table 1 NOACs dosage and recommendations in CKD

*ESC recommendations
a) The SmPc specifies dose reduction from 5 to 2.5mg BID if two of the three criteria are fulfilled :age≥80years,weight ≤60kg, serum creatinine>1.5mg/dL.
b) FDA provided a boxed warning that ‘edoxaban should not be used in patients with CrCl>95mL/min’. EMA advised that ‘edoxaban should only be used in patients with high CrCl
after a careful evaluation of the individual thrombo-embolic and bleeding risk’because of a trend towards reduced benefit compared to Vitamin K antagonists.
c) **A 5mg twice daily dose of apixaban is suggested for patients with CrCl<15ml/min/m2 based on a small single dose pharmacokinetic and pharmacodynamic (anti-Xa activity)
study. However due to lack of sufficient clinical studies regarding long term safety , apixaban should be used with caution in patients with ESRD
d) ESRD= end stage renal disease, RRT= Renal replacement therapy

GCDC 2017