Population
We identified adult patients (aged 18 or over) with AF from January 1, 2013, to December 31, 2017. AF was detected by searching for the International Classification of Diseases, 9th Revision (ICD-9) codes 427.3, 427.31 or 427.32, or the International Classification of Diseases, 10th Revision (ICD-10) code I48.29,30 The first instance of AF coding was used to determine eligibility. The cohort was subsequently restricted to patients who filled a new prescription for rivaroxaban (15 mg or 20 mg once daily), apixaban (2.5 or 5.0 mg twice daily) or warfarin within a year of AF diagnosis. Few patients had a new prescription of either dabigatran or edoxaban and so were not included in our analysis. The date of the first OAC claim was defined as the date of cohort entry. New OAC users were defined as those not exposed to any OACs in the year prior to the claim index date. Patients were also required to have had pharmacy coverage for at least 12 months and enrolment in a drug health insurance plan for at least one year before cohort entry.
We also excluded patients with a code for any condition or procedure that might have impacted the choice of OAC and duration of treatment at discharge: cardiac valve replacement or valve procedures in the five years before cohort entry; end-stage CKD (meaning being on dialysis), kidney transplant, dialysis or coagulation deficiency in the three years before cohort entry; medical procedures (including cardiac catheterization, stent, coronary artery bypass grafting, cerebrovascular or defibrillator) in the three months before cohort entry; deep vein thrombosis or orthopedic surgery in the six months before cohort entry.
Lastly, the cohort was restricted to patients with stage III CKD, as defined by a composite variable covering the ICD code, drug use, and consultations with a nephrologist (as identified in the administrative databases). This composite variable has been validated, with reference to medical chart reviews of older adults with CKD (the algorithm used for estimated glomerular filtration rate (eGFR) definition had a positive predictive value ranging from 94.5% to 97.7%).31