Stroke/SEE, Major Bleeding Reduced With DOAC Therapy in Elderly, Very Elderly AF Patient Populations

elderly man walking, exercise
elderly man walking, exercise
To clarify the real-world clinical status and prognosis of elderly and very elderly non-valvular atrial fibrillation (NVAF) patients, more than 30,000 elderly patients with NVAF aged ≥75 years were enrolled in the ANAFIE Registry.

Direct-acting oral anticoagulant (DOAC) therapy is significantly associated with lower rates of stroke/systemic embolic events (SEE), major bleeding, and all-cause death compared with well-controlled warfarin therapy in elderly and very elderly patients with nonvalvular atrial fibrillation (AF). That is the conclusion of investigators whose research was published in the European Heart Journal Quality of Care and Clinical Outcomes.

To elucidate the real-world clinical status and prognosis of both elderly and very elderly patients with nonvalvular AF, researchers conducted a multicenter, prospective, observational study using the ANAFIE registry, which includes data from more than 30,000 patients older than 75 years of age with nonvalvular AF.

The total cohort included 32,275 patients (57.3% men; mean age, 81.5 years) for analysis, with 1109 patients lost to follow-up and 762 patients who discontinued participation. The mean duration of follow-up was 1.88 years.

Most patients were between 75 and 79 years of age (40%) or 80 and 89 years of age (43.5%); 6.5% were aged over 90 years. The most common type of AF was paroxysmal AF, followed by persistent and long-standing persistent/permanent AF. The most common comorbidities included hypertension and heart failure (75.3% and 37.5%, respectively).

In total, 92.4% of patients were receiving OAC therapy. Among these patients, 25.5% were using warfarin and 66.9% were using DOACs. Patients not taking OACs (7.6%) were the oldest, followed by the warfarin and DOAC groups.

The 2-year incidence of the primary study endpoints (stroke/SEE) was 3.01%, with lower incidence among patients younger than 85 years compared with patients 85 years of age and older. The incidences of major bleeding and intracranial hemorrhage were 2.00% and 1.40%, respectively, and were higher in the group of patients aged 85 years and older.

The incidence of cardiovascular events was 2-fold higher in those 85 and older, and the 2-year incidences of all-cause death and cardiovascular death were 6.95% and 2.03%, respectively. Compared with patients younger than 85 years, the incidences of all-cause and cardiovascular death were “nearly tripled” in the group of patients 85 years and older.

Risks of stroke/SEE, stroke, and ischemic stroke were higher in the No OAC group but lower in the DOAC group, compared with the warfarin group; major bleeding and intracranial hemorrhage risks were lower in the No OAC and DOAC groups compared with the warfarin group, but all bleeding and gastrointestinal bleeding were comparable between the warfarin and DOAC groups.

Both all-cause death and net clinical outcome were significantly higher in patients in the No OAC group and lower in the DOAC group compared with those taking warfarin.

Results of a Cox multivariate regression analysis for variables other than anticoagulation therapy type identified numerous independent risk factors; history of cerebrovascular disease was a significant risk factor for both stroke/SEE and major bleeding and severe liver function disorder was a significant risk factor for major bleeding. Independent risk factors for all-cause death varied and “included factors other than those for stroke/SEE and major bleeding,” the authors wrote.

Study limitations, the investigators said, include a lack of generalizability outside of the study population, no accounting for OAC changes during the follow-up period, and a relatively high proportion of patients lost to follow-up compared with randomized controlled trials.

“The rates of stroke/SEE, major bleeding, and all-cause death were observed less frequently in patients receiving DOACs as compared with patients well-controlled with warfarin,” the researchers concluded. “These results can help inform appropriate management of the growing elderly and very elderly [nonvalvular AF] patient population worldwide.”

Disclosure: This clinical trial was supported by Daiichi Sankyo Co. Ltd. Please see the original reference for a full list of authors’ disclosures.


Yamashita T, Suzuki S, Inoue H, et al. Two-year outcomes of more than 30,000 elderly patients with atrial fibrillation: results from the All Nippon AF In the Elderly (ANAFIE) Registry. Eur Heart J Qual Care Clin Outcomes. Published online April 2, 2021. doi:10.1093/ehjqcco/qcab025