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

BackgroundDirect 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 ResultsWe 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.ConclusionsIn 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.

Trends and Variation in Oral Anticoagulant Choice in Patients with Atrial Fibrillation, 2010–2017

“…Third, the claims we used may have coding errors that led to misclassifications of patients with nonvalvular AF. However, the ICD codes for nonvalvular AF were commonly used in studies using claims and registry data . Fourth, although we were able to identify OAC prescriptions from the claims, we do not know whether the patients actually took these drugs.…”

“…The first fill date for any of these drugs during that period was designated as the index date. Eligibility requirements included continuous enrollment in a medical and pharmacy plan for at least 12 months prior to the index date to ensure completeness of claims information and at least one inpatient or outpatient AF diagnosis ( International Classification of Diseases, Ninth Revision, Clinical Modification [ICD‐9‐CM] code 427.31 or ICD‐10‐CM code I48.0, I48.1, I48.2, or I48.91) within 12 months before the index date. The ICD code performed relatively well with a median positive predictive value of 89% in previous validation studies .…”

Efficacy and Safety of Edoxaban in Patients With Active Malignancy and Atrial Fibrillation: Analysis of the ENGAGE AF‐TIMI 48 Trial

“…The European Society of Cardiology recommends consideration of a DOAC as first‐line therapy in patients with AF for stroke prevention 13. Use of DOACs in patients with AF is increasing in clinical practice and the aging population 36, 37. Older patients receiving DOACs may develop a new or recurrent malignancy because of shared risk factors with aging 3, 4, 5, 6.…”

An Integrated Management Model of Patients With Atrial Fibrillation: The Experience of the Local Health Unit Tuscany North-West

“…The advent of NOACs has improved the management of patients with NVAF by overcoming the limitations associated with traditional OAC drugs. Safety, efficacy, and effectiveness of NOACs have been confirmed by meta-analyses of randomized trials [16,[25][26][27][28][29] and realworld studies [30][31][32][33]. In addition to the effects on clinical outcomes (decreased risk of stroke, bleedings, and death compared to warfarin), NOACs are associated with rapid onset of action, fixed dosing, no need for INR monitoring, and fewer food and drug interactions.…”