Kidney dysfunction is commonly associated with a heart condition characterized by irregular heartbeat, atrial fibrillation (AFib), and affects approximately 50% of individuals with AFib. As the global prevalence of AFib is projected to rise 66% over a 30-year period to 63 million cases globally by 2050, more individuals will be co-diagnosed with AFib and chronic kidney disease (CKD). The co-occurrence of AFib and CKD is associated with an increased risk of stroke, progression of AFib, and mortality over AFib or CKD alone. Furthermore, the therapeutic management of individuals with AFib is complicated by CKD, as renal impairment also decreases the clearance of most anticoagulants – predisposing patients to drug-related toxicities, particularly bleeding risks.
The publication of landmark clinical trials has shown that certain agents used to prevent blood clot formation (i.e. anticoagulants) – such as direct oral anticoagulants (DOACs) have favourable stroke and bleeding benefit over vitamin K antagonists (VKAs) in patients with mild to moderate kidney dysfunction.5-9 However, it is currently unclear whether these benefits observed in clinical trials have resulted in a quantifiable change in prescribing patterns of anticoagulant agents, especially in individuals with CKD. The overall purpose of this proposal is to examine the trends in the use of anticoagulants in patients with AFib between 2000-2021 and compare these trends in patients with and without CKD. We will examine the historical use of anticoagulant therapies and estimate how these landmark clinical trials have impacted prescribing patterns.
Renal disease is a common complication of Atrial fibrillation (AFib) that affects 50% of individuals with AFib. As the global prevalence of AFib is projected to rise 66% over a 30-year period to 63 million cases globally by 2050, more individuals will be co-diagnosed with AFib and chronic kidney disease (CKD). The co-occurrence of AFib and CKD augurs a long-term clinical course characterized by a paradoxical rise in both thromboembolic and haemorrhagic events, resulting in an increased risk of all-cause mortality over AFib or CKD alone. The publication of clinical trials has shown that certain anticoagulants – such as direct oral anticoagulants (DOACs) have a favourable thromboembolic and haemorrhage profile over warfarin in patients with mild-moderate renal dysfunction. However, the selection of anticoagulant in patients with more advanced stage of CKD (e.g. Stage 4 CKD) remains controversial because (1) evidenced-based recommendations in AFib patient with severe CKD are insufficient because of sparse clinical trial data, and (2) observational cohort studies report conflicting results. The overall purpose of this proposal is to examine the trends of anticoagulant use in AFib patients between 2010-2021 and compare these trends in patients with and without CKD. We will achieve this objective by conducting serial cross-sectional studies (by year) describing the trends in the patterns of initiation of anticoagulants. We will empirically analyze the trends of anticoagulant initiation over the study period by conducting trend analysis (e.g. Cochrane Armitage test) and report the corresponding p-values. These analyses will be reported for the overall cohort and within the pertinent subgroups of interest (e.g. CKD stages, age categories, etc).
Findings emanating from this study will enhance our understanding of anticoagulant utilization in
UK patients with concomitant AFIB and CKD, and more broadly, how newer drug therapies are adopted in clinical practice, especially among those with kidney impairment.
The primary study outcome of interest is the choice of anticoagulant initiated (i.e., DOAC vs warfarin) among AFib patients. Secondary outcomes of interest include use of individual DOACs of interest (e.g., apixaban). The primary patient characteristic of interest is the presence of CKD.
Julia Liaw - Chief Investigator - Rutgers, The State University of New Jersey
Julia Liaw - Corresponding Applicant - Rutgers, The State University of New Jersey
Chintan Dave - Collaborator - Rutgers, The State University of New Jersey