More than 1.5 million Americans have advanced chronic kidney disease or irreversible kidney failure requiring dialysis or kidney transplantation. Atrial fibrillation is the most common heart rhythm disorder which is particularly common among patients with kidney disease: more than a quarter of patients with irreversible kidney failure have atrial fibrillation. Persons with atrial fibrillation are at increased risk of thromboembolic events, especially stroke, and death. Oral anticoagulation (blood dilution using pills) has been shown to reduce these risks in the general population free from advanced kidney disease. While warfarin, a vitamin K blocker, has been the mainstay treatment for this, it is marred by important shortfalls including numerous interactions with other drugs or foods and the need to frequently monitor treatment through regular blood tests and adjust the dose. However, since 2010 a new class of drugs has come to market and started to replace warfarin. These so called direct oral anticoagulants (DOACs) do not require blood monitoring, have fewer interactions, and can be taken at a fixed dose. However, the evidence is lacking on various strategies for the prevention of ischemic stroke and mortality in patients with advanced kidney disease who also have atrial fibrillation. The proposed project will focus on a comprehensive evaluation of the effectiveness and safety of these newer DOACs in patients with advanced chronic kidney disease and among those with irreversible kidney failure. We will examine all hypotheses in 2 populations: a) Aim 1: Medicare- insured persons with diagnosed chronic kidney disease stages 4 or 5 (not on dialysis); and b) Aim 2: persons with irreversible kidney failure undergoing dialysis. Patients will be required to also be diagnosed with atrial fibrillation. We will then compare the occurrence of important events between persons receiving warfarin to persons using one of the DOACs. Study outcomes of interest will include stroke, heart attacks, bleeding events, and deaths.
In Aim 3, we will identify patients on dialysis with newly diagnosed with atrial fibrillation who had previously not taken any oral anticoagulation and compare the same outcomes between patients who initiated DOAC treatment to otherwise similar patients not initiating any oral anticoagulation. We will use sophisticated statistical methods and analyses to achieve fair comparisons between treatment groups, as much as is possible without conducting a randomized experiment. Our findings will fill an important evidence gap and have the potential to immediately influence clinical practice, thus improving patient outcomes.

Public Health Relevance

The effectiveness and safety of newer medications (direct oral anticoagulants) for the prevention of stroke and other adverse outcomes in patients with atrial fibrillation has not been sufficiently studied in the high-risk population of patients with advanced chronic kidney disease or those with irreversible kidney failure. The proposed project will conduct a comprehensive evaluation of these newer drugs compared with an older drug, warfarin, which has been the mainstay for this indication. The findings from this work will fill an important evidence gap and have the potential to immediately influence clinical practice, thus improving patient outcomes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK095024-07
Application #
10084289
Study Section
Kidney, Nutrition, Obesity and Diabetes Study Section (KNOD)
Program Officer
Abbott, Kevin C
Project Start
2012-08-01
Project End
2023-12-31
Budget Start
2021-01-01
Budget End
2021-12-31
Support Year
7
Fiscal Year
2021
Total Cost
Indirect Cost
Name
Baylor College of Medicine
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030
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