anticoagulation in patients with renal impairment...anticoagulation in patients with severe renal...

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…