Marie Bradley, PhD, MPharm, MScPH, on Apixaban and Warfarin for Stroke Prevention in Patients With NVAF
In patients of all ages with nonvalvular atrial fibrillation (NVAF), apixaban yielded better results than warfarin for stroke prevention with reduced risk of ischemic stroke, gastrointestinal bleeding, and intracranial hemorrhage, according to the results of a recent study.1
To examine the benefit risk of the 2 medications across various age groups, the researchers conducted a retrospective cohort study in the FDA Sentinel system. After propensity score matching 55,038 patients with NVAF, who initiated apixaban and 55,038 who initiated warfarin between December 2012 and June 2018, were included.
To learn more about this study and its findings, Consultant360 reached out to the lead study author Marie Bradley, PhD, who is a senior pharmacoepidemiologist at the US Food and Drug Administration (FDA) in Silver Spring, Maryland.
Consultant360: Your study examined whether the favorable benefit risk of using apixaban compared with warfarin for stroke prevention in patients with NVAF varied by age. Why is this an important objective to examine?
Marie Bradley: NVAF tends to be a disease of older age, and previous studies examining the benefit risk profile of apixaban compared with warfarin in patients with NVAF using real-world data were mostly restricted to patients aged 65 years or older. Patients with NVAF aged younger than 65 years may have different treatment requirements, and there is a paucity of real-world data examining the safety and effectiveness of apixaban in this age group. The FDA Sentinel System is a large, nationally distributed database that comprises electronic health care data for about 350 million unique patient identifiers, spans the years 2000 to 2020, and captures health care claims for a large sample of NVAF patients aged younger than 65 years and older than 65 years.
We used the FDA Sentinel System to examine the benefit risk profile of apixaban compared with warfarin across the age spectrum of patients with NVAF. As apixaban use has been increasing over time in all age groups, it was important to examine whether important clinical or safety-related differences exist that might lead prescribers and patients to choose apixaban over warfarin.
C360: What is the current standard of care for managing the risk of stroke and bleeding in patients with atrial fibrillation? Does the current standard of care vary by age group?
MB: In the United States, the American College of Cardiology (ACC) and American Heart Association (AHA) in collaboration with the Heart Rhythm Society (HRS) published Clinical Practice Guidelines for the Management of Patients with Atrial Fibrillation in 20142 and also a Focused Update in 2019.3 Included in these guidelines are recommendations regarding anticoagulant therapy for patients with NVAF. While the guidelines do not vary by age explicitly, they do recommend use of the CHA2DS2-VASc score, which takes account of age (ages 65-74 years adds +1 and ages 75 years and older adds +2 to the composite score) to characterize the risk of stroke associated with NVAF for individual patients when considering treatment options. The ACC/AHA/HRS guidelines also provide some information regarding anticoagulant therapies and bleeding risk, and reference the use of the HAS-BLED score, which includes an age category of older than 65 years, that adds to the composite score and corresponds to increased bleeding risk.
C360: Your study found that across all age groups, patients with NVAF had a decreased risk of gastrointestinal bleeding, intracranial hemorrhage, and ischemic stroke in those who initiated apixaban. Was this a result that surprised you, or did you anticipate this?
MB: The results of our study are largely consistent with the results of previous studies4 that examined safety and effectiveness of apixaban compared with warfarin in real-world settings but were restricted to those aged 65 years or older. Therefore, we were not surprised that the findings in our study population were consistent.
C360: What knowledge gaps remain concerning the use of apixaban for stroke prevention?
MB: What remains unknown in this age group is how the benefit harm profile for apixaban compares with other novel oral anticoagulants (NOACs) used in the treatment of NVAF (eg, rivaroxaban and dabigatran). No head-to-head randomized trials have been conducted to determine whether any of the NOACs differ from the others on their effects on stroke and bleeding.
A previous real-world data study4 conducted in the CMS Medicare data source among NOAC initiators for NVAF aged 65 years or older found that dabigatran and apixaban were associated with a more favorable benefit harm profile than rivaroxaban. Specifically, rivaroxaban was associated with an increased risk of intracranial hemorrhage compared with dabigatran and with increased risks of major extracranial bleeding and death compared with dabigatran or apixaban. It is critical to conduct similar studies in younger NOAC users aged younger than 65 years to detect any clinically important differences, which may lead prescribers and patients to prefer one NOAC over the others for treatment of NVAF.
- Bradley M, Welch EC, Eworuke E, Graham DJ, Zhang R, Huang TY. Risk of stroke and bleeding in atrial fibrillation treated with apixaban compared with warfarin. J Gen Intern Med. 2020;35:3597-3604. doi:/10.1007/s11606-020-06180-8
- January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on the practice guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2014;64(21):e1-e76. doi:/10.1016/j.jacc.2014.03.022
- January CT, Wann SL, Calkins H, et al. 2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on clinical practice guidelines and the Heart Rhythm Society in collaboration with the Society of Thoracic Surgeons. Circulation. 2019;140:e125-e151. http://doi.org/10.1161/CIR.0000000000000665
- Graham DJ, Baro E, Zhang R, et al. Comparative stroke, bleeding, and mortality risks in older Medicare patients treated with oral anticoagulants for nonvalvular atrial fibrillation. Am J Med. 2019;132(5):596-604. https://doi.org/10.1016/j.amjmed.2018.12.023