Comparisons between Oral Anticoagulants among Older Nonvalvular Atrial Fibrillation Patients

Abstract

OBJECTIVES Older adult patients are underrepresented in clinical trials comparing non–vitamin K antagonist oral anticoagulants (NOACs) and warfarin. This subgroup analysis of the ARISTOPHANES study used multiple data sources to compare the risk of stroke/systemic embolism (SE) and major bleeding (MB) among very old patients with nonvalvular atrial fibrillation (NVAF) prescribed NOACs or warfarin. DESIGN Retrospective observational study. SETTING The Centers for Medicare & Medicaid Services and three US commercial claims databases. PARTICIPANTS A total of 88 582 very old (aged ≥80 y) NVAF patients newly initiating apixaban, dabigatran, rivaroxaban, or warfarin from January 1, 2013, to September 30, 2015. MEASUREMENTS In each database, six 1:1 propensity score matched (PSM) cohorts were created for each drug comparison. Patient cohorts were pooled from all four databases after PSM. Cox proportional hazards models were used to estimate hazard ratios (HRs) of stroke/SE and MB. RESULTS The patients in the six matched cohorts had a mean follow‐up time of 7 to 9 months. Compared with warfarin, apixaban (HR = .58; 95% confidence interval [CI] = .49‐.69), dabigatran (HR = .77; 95% CI = .60‐.99), and rivaroxaban (HR = .74; 95% CI = .65‐.85) were associated with lower risks of stroke/SE. For MB, apixaban (HR = .60; 95% CI = .54‐.67) was associated with a lower risk; dabigatran (HR = .92; 95% CI = .78‐1.07) was associated with a similar risk, and rivaroxaban (HR = 1.16; 95% CI = 1.07‐1.24) was associated with a higher risk compared with warfarin. Apixaban was associated with a lower risk of stroke/SE and MB compared with dabigatran (stroke/SE: HR = .65; 95% CI = .47‐.89; MB: HR = .60; 95% CI = .49‐.73) and rivaroxaban (stroke/SE: HR = .72; 95% CI = .59‐.86; MB: HR = .50; 95% CI = .45‐.55). Dabigatran was associated with a lower risk of MB (HR = .77; 95% CI = .67‐.90) compared with rivaroxaban. CONCLUSION Among very old NVAF patients, NOACs were associated with lower rates of stroke/SE and varying rates of MB compared with warfarin. J Am Geriatr Soc 67:1662–1671, 2019

Clinical Outcomes of Direct Oral Anticoagulants and Warfarin in Japanese Patients with Atrial Fibrillation Aged ≥ 85 Years: A Single-Center Observational Study

“…Our results show that the annual rates of major bleeding in patients with NVAF aged ≥ 85 years were 3.1 and 4.2/100 PY with DOACs and warfarin, respectively. These incidences were comparable to those associated with OAC therapy in previous studies (ARISTOPHANES 4.9–8.5/100 PY; PREFER in AF 4.0–4.2/100 PY; START2-REGISTER 2.2–2.5/100 PY; Shinohara et al 1.5/100 PY; Yamaji et al 2.5–5.0%/year) [ 13 , 17 , 32 – 34 ]. Interestingly, gastrointestinal bleeding was the most common cause of major bleeding, followed by subdural hemorrhage and traumatic hemorrhage in our very elderly patients.…”

“…Our results showed that the annual rates of ischemic stroke or systemic embolism in patients with NVAF aged ≥ 85 years were 1.8 and 2.2/100 PY with DOACs and warfarin, respectively. A retrospective analysis from a US database study (ARISTOPHANES) showed that the annual rates of ischemic stroke or systemic embolism in patients with NVAF aged ≥ 80 years (mean CHA 2 DS 2 -VASc score 4.7–4.8) were 1.4–1.6 and 2.0–2.1/100 PY with DOACs and warfarin, respectively [ 17 ]. A subanalysis of a European registry study (PREFER in AF) showed an annual rate of thromboembolic events of 4.3/100 PY in patients with NVAF aged ≥ 85 years (mostly taking vitamin K antagonists; mean CHA 2 DS 2 -VASc score 4.7) [ 13 ].…”

“…We found no differences in the incidence rates of thromboembolic or bleeding events between patients treated with DOACs and those treated with warfarin. Recent studies suggested a greater benefit of DOACs over warfarin in very elderly patients with NVAF because DOACs were associated with a lower risk of major bleeding [ 13 – 17 , 33 ]. However, some studies suggested that the incidence of major bleeding was similar between elderly patients treated with DOACs and those treated with warfarin and that warfarin is still preferred over DOACs in patients aged ≥ 90 years who have a high thromboembolic and bleeding risk [ 32 , 34 , 38 ].…”

“…Previous large cohort and randomized controlled studies have shown that warfarin therapy within a recommended prothrombin time-international normalized ratio (PT-INR) range (2.0–3.0) was effective, even in elderly patients with NVAF, without an increased risk of bleeding compared with the risks associated with other antithrombotic therapies [ 11 , 12 ]. In the era of direct oral anticoagulants (DOACs), recent studies suggested the benefit of OACs and the usefulness of DOACs over warfarin, even for very elderly patients with NVAF [ 13 – 17 ]. Asian patients, including Japanese patients, have a higher risk of intracranial hemorrhage than white patients [ 18 , 19 ].…”

Effectiveness and Safety of Oral Anticoagulants in Older Patients With Atrial Fibrillation: A Systematic Review and Meta-Analysis

“…Moreover, in line with randomized studies, differences in safety outcomes between NOACs were seen. Apixaban was associated with a significantly lower major bleeding and intracranial bleeding risk as compared to VKAs in ≥75 and ≥80 year old AF patients (Deitelzweig et al, 2019;Hohmann et al, 2019;Alcusky et al, 2020;Wong et al, 2020). Importantly, as the ARISTOTLE trial did not provide data on the gastrointestinal bleeding risk of apixaban in older AF patients, observational studies were reassuring, illustrating a similar (Wong et al, 2020).…”