chronic kidney disease is associated with increased risk of both thrombosis and bleeding, so in CKD patients with AF it is a challenging problem whether to be anticoagulated or not

2. Anticoagulation in AF
• Anticoagulant therapy is effective in reducing the risk of systemic
embolization in patients with nonvalvular atrial fibrillation (AF)
• Anticoagulation reduces the risk of ischemic stroke (and other
embolic events) by about two-thirds irrespective of baseline risk.
• In a recent study, the annual risk of ischemic stroke in untreated
patients was 0.2, 0.6, and 2.2 percent for those with cha2ds2-vasc
scores of 0, 1, and 2

3. Anticoagulation in AF
• The major safety concern with the use of all antithrombotic agents is the
increased risk of bleeding, especially major bleeding, which includes
events that require hospitalization, transfusion, surgery, or involves
particularly sensitive anatomic locations.
• Intracranial hemorrhage (ICH) is the most serious bleeding complication
since the likelihood of mortality or subsequent major disability is
significantly higher than bleeding at other sites. In most existing studies,
this risk is about 0.2 to 0.4 percent per year.
• While this risk is not trivial, it is markedly lower than the risk of ischemic
stroke in the majority of nonanticoagulated AF patients with CHA2DS2-

4. ASSESSMENT OF INDIVIDUAL
PATIENT RISK

5. EMBOLIC RISK

6. EMBOLIC RISK
Annual stroke rateCHA2DS2-VASc score
0.2 %0
0.6%1
2.2%2
3.2%3
4.8%4
7.2%5
9.7%6
11.2%7
10.8%8
12.2%9
Modified from European society of cardiology guidelines for management of AF

7. BLEEDING RISK
• Multiple observational studies and randomized trials report the risk of ICH
attributable to anticoagulant therapy with warfarin to be in the range of 0.2 to 0.4
percent per year. However, for patients with the following clinical problems, the
risk is significantly higher:
• Thrombocytopenia or known coagulation defect associated with bleeding
• Active bleeding or recent surgery with a concern for ongoing bleeding
• Prior severe bleeding (including ICH) while on an oral anticoagulant
• Suspected aortic dissection
• Malignant hypertension
• Combined use of anticoagulant and antiplatelet agents

8. HAS-BLED bleeding risk score
Bleeds per 100
patient-year
Total
score
point
s
Clinical characteresticslette
r
1.13 %01Hypertension
(ie, uncontrolled blood pressure)
H
1.02%11 or 2
Abnormal renal and liver function
(1 point each)
A
1.88%21StrokeS
3.74%31Bleeding tendencyB
8.7%41
Labile INRs (for patients taking
warfarin)
L
Insufficient data5 to 9
1Elderly (age greater than 65 years)E
1 or 2
Drugs (concomitant aspirin or
NSAIDs) or excess alcohol use (1
point each)
D

9. SHOULD THE PATIENT BE
ANTICOAGULATED?

10. Should the patient be anticoagulated?
• anticoagulant therapy lowers the risk of clinical embolization in all patients with AF,
but its use is associated with an increased risk of bleeding.
• When the bleeding risk outweighs the benefit, avoidance of anticoagulation should be
considered
• When benefits outweigh bleeding risk, anticoagulation is given according to
CHA2DS2-VASC Score :
CHA2DS2-VASc score Recommended therapy
0 No therapy
1
• No therapy, or
• aspirin 81-325 mg daily, or
• anticoagulation therapy
(eg, warfarin [international normalized
ratio (INR) goal 2-3], dabigatran,
rivaroxaban, apixaban, edoxaban)
≥2 Anticoagulation therapy

11. Anticoagulant Drugs

12. Anticoagulant Drugs

13. Anticoagulant drugs
• Situations in which it is preferred to use warfarin instead of the NOAC agents:
Patients already on warfarin who are comfortable with INR measurement and whose INR has
been relatively easy to control with an annual time in the therapeutic range of at least 65
percent
Patients with prosthetic heart valves, those with rheumatic mitral valve disease, mitral stenosis
of any origin, or those with other valvular lesions associated with moderate to severe heart
failure that might lead to valve replacement
incompliance with twice daily dosing of dabigatran or apixaban and unable to take
rivaroxaban or edoxaban.
Patients for whom the NOAC agents will lead to an unacceptable increase in cost.
Patients with chronic severe kidney disease whose estimated glomerular filtration rate is less
than 30 ml/min. However, apixaban is approved for use in the united states for patients with

14. Anticoagulation in CKD
patients with AF

15. AF in CKD patients
• AF is common in patients with CKD, particularly those with ESRD.
• The prevalence of AF is between 8 and 34 percent in patients on hemodialysis
and approximately 7 percent in patients undergoing peritoneal dialysis. This
rate is 10- to 20-fold higher than in the general population
• The presence of either AF or CKD increases the risk of systemic
thromboembolism and ischemic stroke
• Antithrombotic therapy and CKD are both associated with an increased risk of
bleeding.
• Thus, the decision to recommend antithrombotic therapy for patients with AF
and CKD requires consideration of the benefits and risks.

16. AF in CKD patients
HU, A., NIU, J., & WINKELMAYER, W. C. (2018, NOVEMBER) IN SEMINARS IN

17. Thromboembolic risk in CKD patients
• Among patients with AF, CKD is a independent predictor of stroke,
and the risk increases as renal function declines.
• The thromboembolic risk in patients with CKD is due to alterations
in the normal hemostatic mechanisms:
o Patients on hemodialysis suffer from changes between hypervolemia and
intravascular volume loss within a few hours (which may increase blood
viscosity), combined with changes in electrolytes during the hemodialysis
procedure.
o Increased atherosclerosis and endothelial damage.
o Activation of the renin-angiotensin-aldosterone system

18. Thromboembolic risk in CKD patients
Piccini et al have argued that because kidney dysfunction was a potent
predictor for stroke and systemic embolism, it should be included in
stroke-risk stratification criteria and proposed the R2CHADS2 stroke-
risk stratification score.
Piccini, Jonathan P., et al. Circulation

19. Bleeding risk in CKD patients
• CKD is also associated with an increased risk of bleeding
complications, particularly from the gastrointestinal tract due to:
• impairment of normal platelet function secondary to factors such as
uremic toxins, abnormal platelet arachidonic acid metabolism, altered
von Willebrand factor, and reduction in intracellular adenosine
diphosphate (ADP) and serotonin
• increase in the frequency of the need for invasive procedures

20. Anticoagulation in CKD with AF
• Vitamin K antagonist therapy is associated with a significant
reduction in the risk of stroke or thrombo-embolism in CKD
patients but the risk of bleeding is also significantly increased.
Thus, the net clinical effect of VKA treatment requires careful
assessment in such patients.
• Anticoagulation can be safely used in AF patients with moderate or
moderate-to-severe CKD [glomerular filtration rate (GFR) ≥15
mL/min]
European Society of cardiology (ESC) guidelines 2016

25. Dose adjustment for NOACs as evaluated in the PHASE III trials (adapted from
Hart et al.

26. CKD STAGE 3
• For AF patients with an eGFR 30 to 59 mL/min/1.73 m2 and a CHADS2 score of 1 or
higher, we recommend chronic anticoagulant therapy (Grade 1B)
• For these patients with a CHADS2 score of 0, we suggest chronic anticoagulant or
aspirin rather than no antithrombotic agent (Grade 2C).
• Patients may reasonably choose no antithrombotic therapy based on either their
concerns for an increase in bleeding risk or other factors.
• In patients for whom anticoagulant therapy is chosen, we recommend an oral direct
thrombin inhibitor or a factor Xa inhibitor, rather than warfarin (Grade 1B).

27. CKD STAGE 4
• As the degree of CKD worsens, the rates of both stroke and bleeding increase.
• only a small number of patients in clinical trials had an eGFR between 15 and 29
mL/min/1.73 m2
• We believe that anticoagulant therapy has a net clinical benefit (the decrease in
embolic events is greater than the increase in bleeding events) in patients with
stage 4 CKD and suggest its use in patients not deemed to be at high bleeding risk
irrespective of CHADS2 score (Grade 2B).
• For these patients with a CHADS2 of 0 (who are rare), some of our authors and
reviewers recommend warfarin while others do not.
• For these patients in whom chronic anticoagulant therapy is chosen, we suggest
warfarin as opposed to NOAC (Grade 2C). For patients who cannot take warfarin,

28. CKD STAGE 5
• We suggest that patients with eGFR less than 15 mL/min/1.73 m2
who are not on dialysis receive the same anticoagulant approach as
patients with eGFR between 15 and 29 mL/min/1.73 m2 (Grade 2C)
• In dialysis patients, there is high uncertainty regarding the net clinical
benefit of oral anticoagulant therapy due to limited evidence and
marked increase in bleeding risk.
• The efficacy and safety of warfarin in dialysis patients have been
evaluated in a small number of observational studies, Most have
found an increased risk of stroke

29. CKD STAGE 5
• we suggest no anticoagulation for most nonvalvular AF patients with end-
stage renal disease (ESRD) who are on dialysis due to the limited data
demonstrating no thromboembolism benefit yet similar or higher bleeding
risk
• However, 2014 AHA/ACC/HRS AF Guideline weakly recommend warfarin in
dialysis patients with CHADS2 VASc score ≥2 (2B).
• Regarding dialysis patients with AF and very high-risk predictors for
thromboembolism, such as known atrial thrombus, valvular/rheumatic heart
disease, prosthetic heart valve, and previous transient ischemic attack or
stroke, we suggest anticoagulation with warfarin (target INR 2 to 3)
AHA/ACC/HRS: American Heart Association/American College of Cardiology/Heart Rhythm

30. Withholding antithrombotic therapy
• Given our uncertainty of the benefit to risk ratio of antithrombotic therapy in
AF patients with an eGFR <30 mL/min/1.73 m2, it is reasonable to not
recommend antithrombotic therapy in the following groups of individuals:
• Patients with a strong preference for no antithrombotic therapy after a full
discussion of the benefits and risk
• Patients at high fall risk
• Patients with prior life-threatening bleeding
• Patients with poorly controlled hypertension
• Patients with a low likelihood of successful INR control

31. 2016 ESC GUIDELINES
• Approximately one in eight dialysis patients suffer from AF, with an incidence rate
of 2.7/100 patient-years.
• AF is associated with increased mortality in patients on dialysis.
• there are no randomized trials assessing OAC in hemodialysis patients, and no
controlled trials of NOAC in patients with severe CKD (CrCL <25–30 ml/min).
• warfarin use was associated either with a neutral or increased risk of stroke in
database analyses of patients on dialysis. In contrast, data from Denmark suggest
a benefit of OAC in patients on RRT
• Hence, controlled studies of anticoagulants (both VKAs and NOACs) in AF patients
on dialysis are needed.

32. KDIGO
• until new data become available, and in contrast to the previous
KDOQI 2005 recommendation routine anticoagulation of CKD 5D
patients with atrial fibrillation for primary prevention of stroke is not
indicated, whereas previous KDOQI recommendations for secondary
prevention and careful monitoring of all dialysis patients receiving
anticoagulation remain valid.
Herzog, Charles A., et al. "Cardiovascular disease in chronic kidney disease. A clinical update from Kidney
Disease: Improving Global Outcomes (KDIGO)." Kidney international 80.6 (2011): 572-586.

36. Observational studies suggest that warfarin was not associated with a clear benefit or harm among patients who
have atrial fibrillation and receive dialysis. These estimates were limited by study heterogeneity including the
inability to account for a number of important confounders such as the time in the therapeutic range. Because of
the high prevalence of atrial fibrillation, stroke, and bleeding complications in this population, well designed
clinical trials of warfarin and other anticoagulants are urgently needed.

38. • Retrospective cohort study through United States Renal Data System
• Included ESKD and AF undergoing dialysis who initiated treatment
with an oral anticoagulant
• 25523 patients (2351 patients on apixaban and 23172 patients on
warfarin)
• Results: there was no difference in the risks of stroke/systemic
embolism between apixaban and warfarin (HR, 0.88; 95% CI, 0.69–
1.12; P=0.29), but apixaban was associated with a significantly
lower risk of major bleeding (HR, 0.72; 95% CI, 0.59–0.87; P<0.001)

39. Hu, A., Niu, J., & Winkelmayer, W. C.(2018,

40. Suggested
approach
CANADIAN JOURNAL OF CARDIOLOGY VOLUME 33, ISSUE 6, JUNE 2017, PAGES 737-746

41. CONCLUSION
• AF is common in CKD patients, and there is increased risk of both stroke and
bleeding.
• Anticoagulation therapy in CKD patietns with AF depends on balancing embolic and
bleeding risk.
• In CKD stage 3, anticoagulation is recommended if CHADS2 score is 1 or higher
(NOAC preferred)
• In CKD stage 4, anticoagulation is weakly recommended irrespective of CHADS2 score
provided that patients have no high bleeding risk (warfarin or apixapan).
• In CKD stage 5 not on dialysis, the same as stage 4
• In dialysis, no anticoagulation except in AF patients with very high risk predictors
(warfarine or apixaban) individualized approach, with careful assessment of the risks
of ischaemic stroke against the risks of bleeding, will help management of patients
who will benefit from OAC