Anticoagulation in chronic kidney disease dr. mohsen el kossi
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Based on the information provided: - Her stroke risk can be assessed using CHA2DS2-VASc score: C = 1 (Congestive heart failure) H = 1 (Hypertension) A = 1 (Age 65-74) D = 1 (Diabetes) S = 1 (Stroke/TIA/TE) V = 0 A = 0 S = 1 (Sex category) c = 2 She has a high stroke risk. - Given her moderate CKD, I would recommend anticoagulation. A NOAC like Apixaban 2.5mg BD could be used given her eGFR of 32ml/min is above the recommended
![Different Equations for CrCl and eGFR
MDRD equation: GFR (mL/min/1.73 m2
)
175 × (Scr)-1.154
× (Age)-0.203
× (0.742 if female) × (1.212
if African American)
CKD-EPI equation: GFR (mL/min/1.73 m2
)
GFR = 141 × min (Scr /κ, 1)α × max(Scr /κ, 1)-1.209 ×
0.993Age × 1.018 [if female] × 1.159 [if black]](https://image.slidesharecdn.com/anticoagulationinchronickidneydiseasedr-171030182102/85/Anticoagulation-in-chronic-kidney-disease-dr-mohsen-el-kossi-32-320.jpg)
Anticoagulation in chronic kidney disease dr. mohsen el kossi
- 1. Anticoagulation in Chronic Kidney Disease Mohsen El Kossi Consultant Renal Physician Doncaster Royal Infirmary
- 2. Indications • Thromboembolic prophylaxis in non valvular AF • Treatment and prophylaxis for VTE • Acute coronary syndrome • Extracorporeal dialysis circulation • Miscellaneous
- 3. AF and CKD • Inverse relationship between eGFR and AF (ARIC and REGARDS studies) • Increased risk of AF with micro and macroalbuminuria • Prevalence between 18-22% in CKD • Coexistence of well recognised risk factors for AF in general population with CKD (DM, Hypertension, heart failure)
- 4. AF in CKD-5D AF prevalence is around 7.7% in HD patients (Winkelmayer et al 2011)
- 5. • Prevalence among HD patients 11.6% • Incidence in HD patients 2.6/100 patient-years • Risk of stroke 5.2 vs 1.9/100 patient-years • Risk of mortality 26.9 vs 13.4/100 patients-years • There was no protective effect of warfarin on stroke risk
- 6. Risk of Stroke in CKD-5D Wang et al; AJKD 2014 Herzog et al; KI 2011 Mortality rate from stroke is X3 higher in dialysis patients compared to the general population
- 7. AF Associated Mortality in HD Population Winkelmayer et al JASN 2011
- 8. CHADS2 Score and Stroke Risk General Population Gage et al JAMA 2001
- 9. Stroke Risk Assessment CHADS-VASC Score
- 10. Stroke Risk • Low: <2%/year • Medium: 2-4%/year • High risk: >4%/year
- 11. Stroke Risk Assessment in CKD • All schemes were not validated in dialysis patients • ATRIA and R2CHADS2incorporate CKD as a risk factor • 80% of CKD-5D have score of >2 on CHADS2 score
- 13. HAS-BLED Score • Hypertension: systolic BP>160mmhg • Abnormal kidney function: – Dialysis, kidney transplant, sCr >200 umol/l • Abnormal liver function: – Chronic hepatitis, Bilirubin>X2, ALT/AST/ALP>X3 • Age>65 years • Labile INR: – Unstable/high INR, <60% in range • Concomitant drugs: NSAIDs, antiplatlets..etc. Pisters et al Chest, 2010
- 14. Risk of Bleeding in CKD • Increased risk of GI and intracerebral bleeding in CKD-5D (20% have major GI bleed in the first 4 years of dialysis) • Interestingly warfarin use was not associated with increased risk of bleeding • Bleeding risk assessment in CKD-5D is not validated • Risk of bleeding in CKD-ND is less clear • SCr>1.5 mg/dl and eGFR <60ml/min increased risk of major bleed or haemorrhagic stroke respectively • Bleeding risk was more common in CKD patients in ROCKET-AF and ARISTOTLE trials Ng et al AJKD, 2013
- 15. Anti-coagulants in Practice • Vitamin K dependent agents (warfarin) • NOACS/DOACS • UFH • LMWH
- 16. Mechanism of Oral Anticoagulation
- 18. LMWH versus UFH • APTT monitoring is required for UFH • Lower risk of osteoporosis with LMWH • Lower risk of HIT with LMWH • Protamine sulphate is antidote for heparin not for LMWH • Heparin blocks both thrombin and factor Xa versus factor Xa only with LMWH • LMWH reduces 20% of clinical events in ACS/non ST elevation myocardial infarction • Less risk of hypertriglyceredemia with LMWH
- 19. Mechanism of Action of LMWH vs UFH
- 20. UFH-1 • Affordability, availability, short half life and presence of antidote • Potential problems: bleeding, anaphylaxis, thrombocytopenia, osteoporosis, hyperkalaemia and hypertriglyceredemia • Alternatives: LMWH, direct thrombin inhibitors, regional heparinization, heparinioids, citrate, and heparin coated dialyzers. Shen and Winklemayer AJKD, 2012
- 21. UFH-2 • Half life is 1 hour in HD which is 30 minutes normally • Dialyzer type and Epo dose can alter this time • Sources porcine (higher risk of anaphylaxis) or bovine (risk of mad cow disease) • 80 reported cases of death in HD because of over sulphated chondritin sulphate • USA: no recommended dosing in HD, weight based, fixed or APTT guided (X1.5)
- 22. Warfarin • Rodent Pesticide (1948) • Inhibits production of vitamin K dependent factors (II,VII,IX,X) • Prevents activation of factor X into Xa • Slow onset of action • Unpredictable anticoagulation effect • Narrow therapeutic window • Cheap, there is antidote
- 23. NOACS/DOACS
- 24. Salient RCTs of NOACs and Warfarin RE-LY Dabigatran (Pradaxa) ROCKET-AF Rivaroxaban (Xarelto) ARISTOTLE Apixaban (Eliquis)
- 26. Risk of Bleeding Message NOACS have a favourable risk/benefit profile versus warfarin Significant reductions in stroke, intracranial bleeding, mortality Similar major bleeding except with slightly increased GI ones.
- 27. Antidote for NOACS Haemodialysis can help with Dabigatran clearance but none of the others
- 28. Exclusion Criteria in NOAC RCTs • CrCl<30 ml/min – RE-LY Dabigatran (Pradaxa) – ROCKET-AF Rivaroxaban (Xarelto) • CrCl<25 ml/min – ARISTOTLE Apixaban (Eliquis) • Others: active liver disease, prosthetic heart valves, pregnancy, valvular AF, higher Aspirin dose
- 29. Warfarin and AF in HD • Wizemann V1 , Tong L, Satayathum S, Disney A, Akiba T, Fissell RB, Kerr PG, Young EW, Robinson BM. Atrial fibrillation in hemodialysis patients: clinical features and associations with anticoagulant therapy. Kidney Int. 2010 Jun;77(12):1098- 106 • Writing group Members; Mozaffarian D, Benjamin EJ, Go AS, et al. Heart disease and stroke statistics-2016 update: a report from American Heart Association. Circulation. 2016;133(4):e38-e360. • Genovesi S1 , Vincenti A, Rossi E, Pogliani D, Acquistapace I, Stella A, Valsecchi MG. Atrial fibrillation and morbidity and mortality in a cohort of long-term hemodialysis patients. Am J Kidney Dis. 2008 Feb;51(2):255-62. • Bonde AN1 , Lip GY2 , Kamper AL3 , Hansen PR1 , Lamberts M1 , Hommel K3 , Hansen ML1 , Gislason GH4 , Torp-Pedersen C5 , Olesen JB6 . Net clinical benefit of antithrombotic therapy in patients with atrial fibrillation and chronic kidney disease: a nationwide observational cohort study. J Am Coll Cardiol. 2014 Dec 16;64(23):2471-82. • Elliott MJ1 , Zimmerman D, Holden RM. Warfarin anticoagulation in hemodialysis patients: a systematic review of bleeding rates. Am J Kidney Dis. 2007 Sep;50(3):433-40. • McAlister FA, Wiebe N, Jun M, Sandhu R, James MT, McMurtry MS, Hemmelgarn BR, Tonelli M. Are Existing Risk Scores for Nonvalvular Atrial Fibrillation Useful for Prediction or Risk Adjustment in Patients With Chronic Kidney Disease? Can J Cardiol. 2017 Feb;33(2):243-252.
- 30. RCTs For AF Anticoagulation in CKD-5D Stroke risk with warfarin in HD with AF varies 0.95-1.5 2.3 fold of increased haemorrhagic stroke with warfarin No difference for ischaemic stroke
- 31. Guidelines Recommendations Bansal et al AJKD 2017
- 32. Different Equations for CrCl and eGFR MDRD equation: GFR (mL/min/1.73 m2 ) 175 × (Scr)-1.154 × (Age)-0.203 × (0.742 if female) × (1.212 if African American) CKD-EPI equation: GFR (mL/min/1.73 m2 ) GFR = 141 × min (Scr /κ, 1)α × max(Scr /κ, 1)-1.209 × 0.993Age × 1.018 [if female] × 1.159 [if black]
- 33. Oral Anticoagulant Dosing in CKD with AF • Dabigatran 110mg BD – Renal impairment (CrCl between 49-30) – Age≥80 or 75 with 1 or more risk of bleeding • Apixaban 2.5 mg BD if two or more of the following – Cr ≥ 133 umol/l, age ≥ 80 and weight ≤60 Kg • Rivaroxaban 15 mg (CrCl between 49-30)
- 34. Can We Use VKA/NOACS in CKD&/or CKD-5D? • Risk assessment as per current stroke schema in the general population (evidence is B level) • Warfarin is safe, effective but unclear to use it with or without heparin during HD • NOACS require further studies to be used in the context of eGFR<15 ml/min/1.73 m2
- 35. Antiplatelets Vs Oral Anticoagulants in IHD Stable IHD no need to use both because of risk bleeding is high without proven evidence of added benefit Unclear how to treat patients with AF and recent ACS +/- PCI
- 36. Stroke Risk and VTE of NOACs vs VKA In CKD AF and Stroke ARISTOTLE J-ROCKET-AF RE-LY ROCKET-AF Subtotal Recurrent VTE EINSTEIN-DVT EINSTEIN-PE RECOVER REMEDY Subtotal Harel et al, JASN 2014 There was no significant difference in stroke or VTE risk in both groups with CrCl<50 ml/min
- 37. Bleeding Risk and VTE of NOACs vs VKA In CKD There was no significant difference in bleeding risk in both groups with CrCl<50 ml/min Harel et al, JASN 2014
- 38. VTE in General Population • Incidence 1-2/1000 patients-years • Mortality rate is around 14% fatal in the first place • PE mortality is around 17.5% in the first 3 month • Postphlepitic syndrome 17-50% and is difficult to treat • Pulmonary hypertension is around 1-3% in the first year after PE • $10000 and 14000 to manage initial DVT & PE respectively
- 39. Risk of VTE Recurrence • Provoked 1-5% in the first year then 1% annually • Unprovoked first VTE 10% in the first year then 5% in the following years • Unprovoked 2nd VTE 15% risk in the first year then 7.5% annually. • Factors increase the risk, unprovoked ≥X2, male, DM, LL paresis, IBD, Osterogen therapy, PE, proximal DVT, eGFR<30 ml/min, high D dimer after anticoagulant cessation, thrompophilia screening for young patients.
- 40. VTE in CKD • Observational study of 0.7 million patients over 10 years • Risk of VTE is increased with increase in albuminuria (HR 1.6) • Risk of VTE is minimally increased with reduced eGFR (15-29 ml/min) HR 1.23 Azmiouch et al AJKD, 2017
- 41. VTE Risk in Five Population Cohorts • PREVEND suggested a link between VTE and albuminuria but ERIC suggested the risk with low eGFR • Combined data from PREVEND, HUNT, CHS, ERIC and TORMSO confirmed the increased VTE risk with CKD or albuminuria • Increase risk was consistent for both provoked and unprovoked VTE • Increased risk was similar in both PE and DVT Mahmoodi et al Circulation, 2012
- 42. CKD and VTE Risk Mahmoodi et al Circulation, 2012
- 43. ACR and VTE Risk Mahmoodi et al Circulation, 2012
- 44. HR of VTE in CKD Mahmoodi et al Circulation, 2012
- 45. Evidence of Efficacy and Side Effects of NOACS in VTE • RECOVER and RECOVER2 Dabigatran is non inferior to VKA with non significant less risk of bleeding • EINSTEIN DVT&PE: Rivaroxiban is non inferior to VKA with less risk of bleeding • AMPLIFY Apixaban: is non inferior to VKA with significant less risk of bleeding • Unclear effect in certain situations, pregnancy, lactation, massive PE or DVT, active malignancy
- 46. Conclusions • Not recommended to use both warfarin and heparin in the dialysis circuit • Not advisable to use antiplatelets and anticoagulants for IHD unless recently placed stents (eluting stents may be preferable) • NOACS can use Apixaban at 2.5 mg BD up to CrCl of 20 ml/min • Use the current stroke risk assessment tool used in the general population
- 47. Research Recommendations by KDOQI Bansal et al AJKD 2017
- 48. Thank You
- 49. Cases
- 50. Cases • 68 years old lady known insulin treated diabetes, AF with previous history of TIA. Her eGFR is 32 ml/min and currently on Aspirin 75 mg OD, Ramipril 2.5 mg OD, Bisoprolol 5 mg/day. • What is her stroke risk? • Would you recommend anticoagulation in her case and which one?