Safety and Efficacy of Apixaban in Severe Renal Impairment
Study Details
Study Description
Brief Summary
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.
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Detailed Description
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
Study Design
Outcome Measures
Primary Outcome Measures
- Clinically significant bleeding [4 years]
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
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Montefiore Medical Center | Bronx | New York | United States | 10467 |
Sponsors and Collaborators
- Albert Einstein College of Medicine
Investigators
- Principal Investigator: Henny H Billett, MD, Albert Einstein College of Medicine and Montefiore Medical Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2017-7774