anticoagulation in patients with renal impairment...anticoagulation in patients with severe renal...
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Anticoagulation in Patients with Severe Renal Impairment
Tony Wan, MD, FRCPC
Clinical Instructor, Division of General Internal Medicine Department of Medicine, University of British Columbia
Objectives
• Discuss the use of direct oral anticoagulant in patients with severe renal impairment
• Discuss the use of low molecular weight heparin in patients with severe renal impairment
Disclosures
Grants from Servier and Bayer for expanding the Thrombosis Clinic at St. Paul’s Hospital
Meet our patient Shannon
86 year old woman with multiple comorbidities including diabetic nephropathy with a CrCl of 21ml/min. She presents with acute pleuritic chest pain, shortness of breath, tachycardia and a normal CXR. BP 140/84. V/Q scan shows mismatch in a segmental distribution consistent with pulmonary embolism. How are you treating her acute pulmonary embolism?
Meet our patient Shannon
86 year old woman with multiple comorbidities including diabetic nephropathy with a CrCl of 21ml/min. She presents with acute pleuritic chest pain, shortness of breath, tachycardia and a normal CXR. BP 140/84. V/Q scan shows mismatch in a segmental distribution consistent with pulmonary embolism. How are you treating her acute pulmonary embolism?
A) Enoxaparin SC with transition to warfarin B) Dalteparin SC with transition to warfarinC) Tinzaparin SC with transition to warfarin D) Unfractionated heparin IV infusion with transition to warfarin E) Rivaroxaban POF) Apixaban POG) Other
Direct Oral Anticoagulants (DOAC)
Medscape
Renal Clearance
Dabigatran Rivaroxaban Apixaban Edoxaban
Renal Clearance (%) 80% 33% 25% 33-50%
Half-life (hours) 12-17 5-9 9-14 9-11
Dialyzability Yes No No No
Kassim N. Journal of Applied Hematology 2015
Apixaban for VTE Treatment and Prevention
• Not recommended in patients with CrCl < 15 ml/min or in those undergoing dialysis
• Use with caution in patients with CrCl 15 – 29 ml/min because limited clinic data indicated that plasma concentrations are increased
Apixaban Monograph 2018
Apixaban for Atrial Fibrillation Renal Function Recommendation
CrCl 25 – 30 mL/min According to the ABC criteria
CrCl 15 – 24 mL/min No dosing recommendation can be made as clinic data is very limited
CrCl < 15 mL/min Not recommended
Dialysis Not recommended
Apixaban Monograph 2018
Apixaban for Atrial Fibrillation
• Dose reduction from 5mg BID to 2.5mg BID for patients with at least 2 of the following characteristics
• Age ≥ 80• Body weight ≤ 60 kg• Serum Creatinine ≥ 133 micromole/L (1.5 mg/dL)
Apixaban Monograph 2018
Hohnloser et al. European Heart Journal 2012
Meta-analysis on Risk of Bleeding with Apixaban in Patients with Renal Impairment
Pathak et al. Am J Cardio 2015
RENAL-AF
NCT02942407
AF with CHA2DS2-VASc ≥ 2 and ESRD on hemodialysis ≥ 3 months
Randomization
Apixaban 5mg BID with reduction for selected patients
Warfarin (INR 2-3)
Time to major bleeding or clinically relevant non-major bleeding eventswith 15 months follow up
RENAL-AF
NCT02942407
AF with CHA2DS2-VASc ≥ 2 and ESRD on hemodialysis ≥ 3 months
Randomization
Apixaban 5mg BID with reduction for selected patients
Warfarin (INR 2-3)
Time to major bleeding or clinically relevant non-major bleeding eventswith 15 months follow up
Estimated completion by 2020
Rivaroxaban Renal Dosing
Rivaroxaban Monograph 2018
Not recommended in patients with CrCl < 15 ml/min
FDA Clinical Pharmacology Biopharmaceutics Review 2011
XARENO
NCT02663076
Patients with non-valvular AF and
eGFR 15 – 49 ml/min
Treating physician to decide on rivaroxaban, warfarin or
no anticoagulation(non interventional)
Efficacy and safety outcomes with 12 month follow up
Low Molecular Weight Heparin (LMWH)
Wood. NEJM 1997
Enoxaparin
Dalteparin
Tinzaparin
LMWH Renal Dosing
Hughes et al. Clin Kidney J 2014
Tinzaparin
• Largest licensed LMWH and the clearance is less dependent on renal function
• Available evidence for tinzaparin demonstrates no accumulation in patients with CrCl level down to 20 mL/min
• Limited data available in patients with CrCl < 20 mL/min
Tinzaparin Monograph 2017
TRIVET Patients with objectively confirmed venous thromboembolism
CrCl 30 – 60ml/min
Tinzaparin 175IU/kg SC daily for 7 days
Primary outcome = Anti-FXa level measured at day 3, 5 and 7Secondary outcome = recurrent VTE and bleeding
CrCl > 60ml/min Dialysis CrCl < 30ml/min
Lim et al. Journal of Thrombosis and Haemostasis 2016
TRIVET
Lim et al. Journal of Thrombosis and Haemostasis 2016
Tinzaparin vs Dalteparin for Periprocedure Bridging in Hemodialysis Patients
Rodger et al. AJKD 2012
Back to our patient Shannon
86 year old woman with multiple comorbidities including diabetic nephropathy with a CrCl of 21ml/min. She presents with acute pleuritic chest pain, shortness of breath, tachycardia and a normal CXR. BP 140/84. V/Q scan shows mismatch in a segmental distribution consistent with pulmonary embolism. How are you treating her acute pulmonary embolism?
A) Enoxaparin SC with transition to warfarin B) Dalteparin SC with transition to warfarinC) Tinzaparin SC with transition to warfarin D) Unfractionated heparin IV infusion with transition to warfarin E) Rivaroxaban POF) Apixaban POG) Other
Take Home Message?
Take Home Message?
Unfortunately we cannot abolish unfractionated heparin
At least not now…