Temporal Trends in the Use and Comparative Effectiveness of Direct Oral Anticoagulant Agents Versus Warfarin for Nonvalvular Atrial Fibrillation: A Canadian Population-Based Study

Abstract

Background: Direct oral anticoagulants (DOACs) are noninferior to warfarin for stroke prevention in atrial fibrillation (AF). We aimed to determine the population risk of stroke and death in incident AF, stratified by anticoagulation status and type, and the temporal trends of oral anticoagulation practice in the post-DOAC approval period.

Methods and results: We conducted a population-based cohort study of incident nonvalvular AF cases using administrative health data in Alberta, Canada. We used Cox proportional hazards modeling with anticoagulation status as a time-varying exposure and adjusted for age (continuous), sex, congestive heart failure, hypertension, diabetes mellitus, prior transient ischemic attack or ischemic stroke, myocardial infarction, peripheral artery disease, and chronic kidney disease. Primary outcome was the composite of stroke and death. Among 34 965 patients with incident AF (56.0% male, median age 73 years), relative to warfarin, DOAC use was associated with decreased risk of all stroke and death (hazard ratio: 0.90; 95% confidence interval, 0.83-0.97) and decreased hemorrhagic stroke (hazard ratio: 0.60; 95% confidence interval, 0.40-0.91]) but a similar risk of ischemic stroke (hazard ratio: 1.12; 95% confidence interval, 0.94-1.34]). During this time period, DOAC use increased rapidly, surpassing warfarin, but the total oral anticoagulation use in the population remained stable, even in the subgroup with the highest thromboembolic risk.

Conclusions: In a real-world population-based study of patients with incident AF, anticoagulation with DOACs was associated with decreased risk of stroke and death compared with warfarin. Despite a rapid uptake of DOACs in clinical practice, the total proportion of AF patients on anticoagulation has remained stable, even in high-risk patients.

Keywords: anticoagulant; atrial fibrillation; mortality; stroke.

Figure 1

Temporal trends of oral anticoagulation prescription and occurrence of ischemic stroke (A), hemorrhagic stroke (B), and death (C). Age–sex adjusted rates per 1000 person‐years. In 2009, the first year of the study, the occurrence of outcomes was high and likely artificially inflated because only patients with incident atrial fibrillation (AF) were included as opposed to the following years in which a combination of incident and prevalent AF patients were followed. Incident AF is often diagnosed in the context of a stroke or other medical condition, leading to higher apparent risk of stroke or death in the immediate period after diagnosis. DOAC indicates direct oral anticoagulant.

Figure 2

Temporal trends of DOAC and warfarin prescriptions stratified by high risk (CHADS ₂ ≥2 or age ≥75 years), moderate risk (CHADS ₂=1 or age 65–74 years), or low risk (CHADS ₂=0 or age <65 years). CHADS ₂ indicates congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke/transient ischemic attack; DOAC, direct oral anticoagulant.

Figure 3

Temporal trends of all oral anticoagulation prescriptions stratified by high risk (CHADS ₂ ≥2 or age ≥75 years), moderate risk (CHADS ₂=1 or age 65–74 years), or low risk (CHADS ₂=0 or age <65 years). CHADS ₂ indicates congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke/transient ischemic attack; DOAC, direct oral anticoagulant.