Safety and Efficacy of Apixaban in Severe Renal Impairment
| Status: | Recruiting |
|---|---|
| Conditions: | Renal Impairment / Chronic Kidney Disease, Renal Impairment / Chronic Kidney Disease |
| Therapuetic Areas: | Nephrology / Urology |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 3/1/2019 |
| Start Date: | May 10, 2017 |
| End Date: | July 10, 2019 |
| Contact: | Margarita Kushnir, MD |
| Email: | mkushnir@montefiore.org |
| Phone: | 7184302145 |
Despite emergence of new anticoagulants over the last few years, patients with advanced
chronic kidney disease still have limited options and are usually managed with warfarin after
venous thromboembolism or diagnosis of atrial fibrillation. The use of all direct oral
anticoagulants is not recommended in patients with creatinine clearance below 15 mL/min.
Apixaban has the lowest fraction of renal excretion (27%) and is sometimes used in patients
with CKD V (GFR < 15 mL/min/BSA) and end stage renal disease (ESRD). Until recently, data on
apixaban use in this population were limited to pharmacodynamics as patients with severe
renal impairment were excluded from clinical trials. In a 2016 study, it was found that ESRD
resulted in 36% increase in apixaban AUC but no increase in Cmax, and that hemodialysis had a
limited impact on apixaban clearance.1 There are now data available on inpatient use of
apixaban vs.coumadin in patients with creatinine clearance below 25 ml/min.2 There was no
significant difference in bleeding events between the two groups but the study period was
limited to a hospital admission and may not reflect bleeding risk of long-term
anticoagulation.
Use of warfarin in patients on hemodialysis entails several disadvantages in this population.
The need for INR monitoring adds clinic visits for patients that already spend a great
portion of their time in healthcare facilities. Numerous drug interactions, involving
warfarin, complicate management of ESRD patients that are often on many medications. The
reduced risk of intracranial bleeding on apixaban, compared to warfarin, in the ARISTOTLE
study, is an important consideration in patients that may already be at increased risk due
other factors such as uremia and concurrent antiplatelet agents.
chronic kidney disease still have limited options and are usually managed with warfarin after
venous thromboembolism or diagnosis of atrial fibrillation. The use of all direct oral
anticoagulants is not recommended in patients with creatinine clearance below 15 mL/min.
Apixaban has the lowest fraction of renal excretion (27%) and is sometimes used in patients
with CKD V (GFR < 15 mL/min/BSA) and end stage renal disease (ESRD). Until recently, data on
apixaban use in this population were limited to pharmacodynamics as patients with severe
renal impairment were excluded from clinical trials. In a 2016 study, it was found that ESRD
resulted in 36% increase in apixaban AUC but no increase in Cmax, and that hemodialysis had a
limited impact on apixaban clearance.1 There are now data available on inpatient use of
apixaban vs.coumadin in patients with creatinine clearance below 25 ml/min.2 There was no
significant difference in bleeding events between the two groups but the study period was
limited to a hospital admission and may not reflect bleeding risk of long-term
anticoagulation.
Use of warfarin in patients on hemodialysis entails several disadvantages in this population.
The need for INR monitoring adds clinic visits for patients that already spend a great
portion of their time in healthcare facilities. Numerous drug interactions, involving
warfarin, complicate management of ESRD patients that are often on many medications. The
reduced risk of intracranial bleeding on apixaban, compared to warfarin, in the ARISTOTLE
study, is an important consideration in patients that may already be at increased risk due
other factors such as uremia and concurrent antiplatelet agents.
This is a retrospective cohort study. The investigators will use Clinical Looking Glass (CLG)
to identify all adult patients with creatinine clearance < 15 ml/min who were treated with
apixaban or warfarin, for at least 1 month, between 3/1/2013 and 3/1/2017. The investigators
will then review electronic charts in Carecast and Epic to gather data about bleeding and
thrombotic events.Primary outcome: clinically significant bleeding, per Control of
Anticoagulation Subcommittee criteria: 1) fatal bleed; 2) symptomatic bleed at anatomically
critical sites such as intracranial, intraspinal, intraocular, or pericardial hemorrhage;
3)symptomatic noncritical bleeds resulting in transfusion of 2 units or more of red blood
cells or drop in hemoglobin of at least 2.0 g/dl.4 Secondary outcomes: venous
thromboembolism, cerebrovascular accident, intracranial hemorrhage, bleeding related to HD
access
to identify all adult patients with creatinine clearance < 15 ml/min who were treated with
apixaban or warfarin, for at least 1 month, between 3/1/2013 and 3/1/2017. The investigators
will then review electronic charts in Carecast and Epic to gather data about bleeding and
thrombotic events.Primary outcome: clinically significant bleeding, per Control of
Anticoagulation Subcommittee criteria: 1) fatal bleed; 2) symptomatic bleed at anatomically
critical sites such as intracranial, intraspinal, intraocular, or pericardial hemorrhage;
3)symptomatic noncritical bleeds resulting in transfusion of 2 units or more of red blood
cells or drop in hemoglobin of at least 2.0 g/dl.4 Secondary outcomes: venous
thromboembolism, cerebrovascular accident, intracranial hemorrhage, bleeding related to HD
access
Inclusion Criteria:
- Patients with creatinine clearance <15 mL/min who are on anticoagulation with apixaban
or warfarin.
Exclusion Criteria:
- Patients without end stage renal disease who are not on anticoagulation with apixaban
or warfarin.
We found this trial at
1
site
3550 Jerome Avenue
Bronx, New York 10467
Bronx, New York 10467
(718) 920-4321
Principal Investigator: Margarita Kushnir, MD
Phone: 718-430-2145
Montefiore Medical Center As the academic medical center and University Hospital for Albert Einstein College...
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