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Frailty and DOAC vs. Warfarin Outcomes in Older Adults With AF
Quick Takes
- Use of direct oral anticoagulants (DOACs) offers similar or reduced risk of adverse events for older patients with atrial fibrillation (AF) as compared to warfarin.
- For frail older patients with AF, use of apixaban may reduce the risk of bleeding, stroke, and death as compared to warfarin.
- Most older patients with AF, even if at increased risk of bleeding due to frailty, likely benefit from anticoagulation therapy.
Study Questions:
What are the outcomes of direct oral anticoagulant (DOAC) use versus warfarin in older patients with atrial fibrillation (AF) by frailty level?
Methods:
The authors conducted an analysis of Medicare beneficiaries with AF who initiated anticoagulation with dabigatran, rivaroxaban, apixaban, or warfarin between 2010–2017. Patients were propensity matched based on anticoagulant used and various demographic and medical characteristics. Patients were matched 1:1 for each frailly category, using the claims-based frailty index and propensity score matching. The outcome of interest was a composite of death, ischemic stroke, or major bleeding.
Results:
The cohort of patients initiated on dabigatran or warfarin (n = 158,730, median follow-up 72 days) experienced a combined primary outcome event rate of 63.5 versus 65.6/1,000 person-years for dabigatran and warfarin, respectively (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.92-1.05). For the nonfrail subcohort, the HR was 0.81 (95% CI, 0.68-0.97), while the prefrail and frail subcohorts did not have a statistically significant HR. The cohort of patients initiated on rivaroxaban or warfarin (n = 275,944, median follow-up 82 days) experienced a combined primary outcome event rate of 77.8 and 83.7/1,000 person-years for rivaroxaban and warfarin, respectively (HR, 0.98; 95% CI, 0.94-1.02). For the nonfrail subcohort, the HR was 0.88 (95% CI, 0.77-0.99), while the prefrail and frail subcohorts did not have a statistically significant HR. The cohort of patients initiated on apixaban or warfarin (n = 218,738, median follow-up 84 days) experienced a combined primary outcome event rate of 60.1 and 92.3/1,000 person-years for apixaban and warfarin, respectively (HR, 0.68; 95% CI, 0.65-0.72). HRs were significantly reduced for the nonfrail, prefrail, and frail subcohorts. Those in the apixaban-warfarin cohort had reduced individual HRs for death and major bleeding regardless of frailty level, while the HR for ischemic stroke was reduced only for the prefrail and frail subcohorts.
Conclusions:
The authors concluded that older adults with AF experienced lower rates of adverse events across all frailty levels with apixaban, but adverse events were only reduced for nonfrail subcohorts treated with either dabigatran or rivaroxaban versus warfarin.
Perspective:
DOACs are recommended as first-line therapy for stroke prevention in AF by numerous professional societies, based largely on a reduced risk of life-threatening bleeding and ease of administration. However, older frail adults may be at increased risk of bleeding-related complications that influence anticoagulant decision making. This large retrospective claims-based analysis suggests that DOAC therapy is at least as good as warfarin for the composite outcome of death, ischemic stroke, and major bleeding. Most importantly, the analysis suggests a lower rate of adverse events among patients treated with apixaban regardless of frailty level. This finding aligns with other large retrospective studies suggesting that apixaban may have a lower overall risk of major bleeding than warfarin when used for stroke prevention in AF. This analysis adds to a growing body of literature suggesting that for most patients with AF, anticoagulation offers overall benefit, even if the patient is felt to be at higher bleeding risk related to frailty. In these patients, use of apixaban may be a good choice, if clinically appropriate.
Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Geriatric Cardiology, Prevention, Anticoagulation Management and Atrial Fibrillation, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias
Keywords: Anticoagulants, Arrhythmias, Cardiac, Atrial Fibrillation, Brain Ischemia, Frail Elderly, Geriatrics, Hemorrhage, Medicare, Secondary Prevention, Stroke, Vascular Diseases, Warfarin
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