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Cardio Diabetes Medicine 2017 553

Novel Oral Anti Coagulants in

Chronic Kidney Disease

Georgi Abraham. MD, FRCP

Priya Haridas A. MBBS
Madras Medical Mission Hospital, Chennai

Abstract tion on warfarin therapy. Coumadin derivatives re-
Chronic kidney disease (CKD) is an emerging cause quire monitoring by prothrombin time and INR which
of cardiovascular morbidity and mortality. As it pre- may vary widely in CKD patients on dialysis giving
dominantly affects the older population with comor- rise to bleeding episodes which could be devastating
bidities such as coronary artery disease, hyperten- at times. However the availability of reversal agents
sion and diabetes mellitus, patients requiring oral like vitamin K, fresh frozen plasma in case of drug
anti coagulation are on the rise. Traditionally Cou- over dose or life threatening bleeding make warfarin
madin derivatives were used for this purpose. Novel suitable for use in CKD patients.[1]
oral anti coagulants such as dabigatran, apixaban, Novel oral anti coagulants are of two classes: Direct
edoxaban, and rivaroxaban are increasingly being thrombin inhibitors and factor Xa inhibitor. All NO-
used for anti coagulation. There is limited data on ACs have a significantly lower risk of intracranial and
their use in various stages of CKD. intracerebral bleeding than w\arfarin. Since that is
the most feared bleeding risk and may be sufficient
Introduction reason to consider switching patients from warfarin
CKD patients have complex issues with regards to to a NOAC, even if they seem to be doing well on
hemostasis . There are diverse group of patients warfarin therapy [3]
who are at various stages of CKD in India. The di- Dabigatran was the first NOACs approved for clini-
alysis group comprising both maintenance hemodi- cal use. It is a direct thrombin factor II inhibitor. The
alysis and chronic peritoneal dialysis have many co FDA approved dose for patients with Creatinine
morbidities such as diabetes mellitus, Hypertension, clearance(CrCl) more than 50ml/min and between
coronary artery disease with associated cardiac ar- 30 and 50ml/min is 150mg and 110mg twice a day.
rhythmias predominantly atrial fibrillation. The immi- In the RE-LY(Randomized Evaluation of Long –Term
nent threat of peripheral embolization mandates anti Anticoagulation Therapy)trial, as compared with war-
coagulation in this subset of patients. Warfarin and farin, the 110-mg dose of dabigatran was associated
other oral anti coagulants have many limitations for with similar rates of stroke and systemic embolism
use in dialysis patients. Novel oral anti coagulants are and lower rates of major hemorrhage; the 150-mg
being used increasingly for anti coagulation in non dose of dabigatran was associated with lower rates
CKD patients. There is limited data on their efficacy of stroke and systemic embolism but with a similar
and safety in CKD patients. rate of major hemorrhage.[4] About 80% of dab-
Long term warfarin use has been associated with a igatran is cleared by the kidneys, hence caution is
condition called warfarin nephropathy and develop- needed when used in patients with CrCl between 30
ment of both acute kidney injury and CKD[1].Warfarin to 50ml/min and is contraindicated in advanced CKD
is not removed by dialysis because 99 % is bound to stages [5] U.S SmPC prohibits the co-administration
plasma proteins.It is cleared by hepatic metabolism. of dabigatran with drugs that inhibit P-glycoprotien
[2] Patients with estimated GFR less than 30ml/min/ due to the potential for drug accumulation.
m2 have a 4.9 fold increase in the risk of bleeding Apixaban is a direct factor Xa inhibitor with 27%renal
when compared to patients with normal renal func- elimination[2]. It is 87% protein bound. Only 6.7% is

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