Apixaban linked to fewer adverse events in older adults with frailty, atrial fibrillation
Among older adults with atrial fibrillation, apixaban was linked to lower rates of adverse events across all frailty levels compared with warfarin, a retrospective observational study showed.
In contrast, dabigatran and rivaroxaban were tied to lower adverse event rates in patients with atrial fibrillation (AF) who were not frail, according to researchers.
“Currently, decisions about anticoagulant therapy are mainly driven by risk assessment models for ischemic stroke and major bleeding without consideration of frailty,” Dae Hyun Kim, MD, MPH, ScD, an associate professor of medicine at the Hebrew Rehabilitation Center in Massachusetts, and colleagues wrote in Annals of Internal Medicine.
“Because of the poor representation of older adults with frailty and the lack of frailty assessment in clinical trials, the role of frailty in the choice between a [direct oral anticoagulant] and warfarin is uncertain, and anticoagulant use remains suboptimal in frail patients with AF,” they added.
The researchers conducted a 1:1 propensity score-matched analysis of Medicare data from 2010 to 2017 to compare outcomes among three groups: dabigatran users vs. warfarin users; rivaroxaban users vs. warfarin users, and apixaban users vs. warfarin users.
Participants who received apixaban had a similar age, mean claims-based frailty index, mean CHA2DS2-VASc (congestive heart failure, hypertension, age greater than 75 years, diabetes mellitus, stroke or transient ischemic attack, vascular disease, age 65 to 74 years, sex category) score and mean comorbidity score compared with warfarin recipients. Meanwhile, those who received dabigatran or rivaroxaban were more likely to be younger and had a lower CHA2DS2-VASc score, lower comorbidity score and lower prevalence of comorbidities vs. warfarin recipients.
On average, frail participants were older, had a higher HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, Labile international normalized ratio, concomitant drugs or alcohol use and being older than 65 years), CHA2DS2-VASc and comorbidity scores, and used more medications, according to the researchers.
After a median of 72 days, Kim and colleagues reported that in 58,730 patients in the dabigatran vs. warfarin group, the rate of death, ischemic stroke or major bleeding for each 1,000 person-years was 63.5 for dabigatran users and 65.6 for warfarin users (HR = 0.98; 95% CI, 0.92-1.05; rate difference [RD] = –2.2; 95% CI, –6.5 to 2.1). Also, in this cohort, the HR was 0.81 (95% CI, 0.68-0.97) among those who were not frail; 0.98 (95% CI, 0.9-1.08) among those who were prefrail; and 1.09 (95% CI, 0.96-1.23) among those who were frail.
In 275,944 patients in the rivaroxaban vs. warfarin group, after a median of 82 days, the rate of death, ischemic stroke or major bleeding per 1,000 person-years was 77.8 for rivaroxaban users and 83.7 for warfarin users (HR = 0.98; 95% CI, 0.94-1.02; RD = –5.9; 95% CI, –9.4 to –2.4). The HR was 0.88 (95% CI, 0.77-0.99) among those who were not frail; 1.04 (95% CI, 0.98-1.1) among those who were prefrail; and 0.96 (95% CI, 0.89-1.04) among those who were frail.
In 218,738 patients in the apixaban vs. warfarin group, after a median of 84 days, the rate of death, ischemic stroke or major bleeding for each 1,000 person-years was 60.1 for apixaban users and 92.3 for warfarin users (HR = 0.68; 95% CI, 0.65-0.72; RD = –32.2; 95% CI, –36.1 to –28.3). The HR was 0.61 (95% CI, 0.52-0.71) among those who were not frail; 0.66 (95% CI, 0.61-0.7) among those who were prefrail; and 0.73 (95% CI, 0.67-0.8) among those who were frail.
“Our study provides evidence to guide the choice of a direct oral anticoagulant versus warfarin for older adults with atrial fibrillation,” Kim and colleagues concluded. “Our novel approach to evaluating heterogeneity of the emulated effectiveness of drug therapy using a [claims-based frailty index] can be extended to claims-based pharmacoepidemiologic studies to generate evidence that is unavailable from clinical trials.”
American College of Cardiology. ACCEL: Assessing Stroke Risk: CHADS2 versus CHA2DS2-VASc. https://www.acc.org/latest-in-cardiology/articles/2013/11/22/14/43/accel-1-2. Accessed July 19, 2021.