Oral anticoagulants for nonvalvular atrial fibrillation in frail elderly patients: insights from the ARISTOPHANES study

Abstract

Background. Patient frailty amongst patients with nonvalvular atrial fibrillation (NVAF) is associated with adverse health outcomes and increased risk of mortality. Additional evidence is needed to evaluate effective and safe NVAF treatment in this patient population. Objectives. This subgroup analysis of the ARISTO-PHANES study compared the risk of stroke/systemic embolism (S/SE) and major bleeding (MB) amongst frail NVAF patients prescribed nonvitamin K antagonist oral anticoagulants (NOACs) or warfarin. Methods. This comparative retrospective observational study of frail, older NVAF patients who initiated apixaban, dabigatran, rivaroxaban or warfarin from 01JAN2013-30SEP2015 was conducted using Medicare and 3 US commercial claims databases. To compare each drug, 6 propensity score-matched (PSM) cohorts were created. Patient cohorts were pooled from 4 databases after PSM. Cox models were used to estimate hazard ratios (HR) of S/SE and MB. Results. Amongst NVAF patients, 34% (N = 150 487) met frailty criteria. Apixaban and rivaroxaban were associated with a lower risk of S/SE VS warfarin (apixaban: HR: 0.61, 95% CI: 0.55-0.69; rivaroxaban: HR: 0.79, 95% CI: 0.72-0.87). For MB, apixaban (HR: 0.62, 95% CI: 0.57-0.66) and dabigatran (HR: 0.79, 95% CI: 0.70-0.89) were associated with a lower risk and rivaroxaban (HR: 1.14, 95% CI: 1.08-1.21) was associated with a higher risk VS warfarin. Conclusion. Amongst this cohort of frail NVAF patients, NOACs were associated with varying rates of stroke/SE and MB compared with warfarin. Due to the lack of real-world data regarding OAC treatment in frail patients, these results may inform clinical practice in the treatment of this patient population.

Antithrombotic therapy in the elderly and senile age: the consensus opinion of experts of the Russian Association of Gerontologists and Geriatricians and the National Society of Preventive Cardiology

“…Апиксабан и дабигатран продемонстрировали сопоставимую с варфарином эффективность и безопасность. В 2020г опубликованы результаты крупного наблюдательного ретроспективного исследования [152] с участием "хрупких" пациентов с ФП, ранее не получавших антикоагулянты. Как и в исследовании Martinez ВК, et al [151], для выявления СА использовали диагностический алгоритм Johns Hopkins Claims-based Frailty Indicator с пороговым значением индекса "хрупкости" ≥0,20.…”

Analysis of low‐dose subgroups receiving NOACs

“…The ARISTOPHANES study [1] is an important contribution to the recognition that the new oral anticoagulants (NOACs) have a role in the management of nonvalvular atrial fibrillation (NVAF), even at doses lower than those recommended in the original studies [2][3][4]. In the original studies, conventional dose apixaban was associated with the same risk of gastrointestinal bleeding as warfarin [2], dabigatran 150 mg BID was associated with greater risk [3], and rivaroxaban with greater risk only if there was no previous history of gastrointestinal bleeding [4].…”

Response to a letter by Jolobe: ARISTOPHANES subgroup analysis of frail and older patients with NVAF receiving low doses of novel oral anticoagulants

“…We would like to thank Oscar Jolobe for his comments on our ARISTOPHANES subgroup analysis [1,2] on frail elderly patients with nonvalvular atrial fibrillation (NVAF). He suggests it would be useful to ascertain whether the lower risk of gastrointestinal (GI) bleeding in the comparison between apixaban and warfarin was evident in the standard-dose apixaban subgroup in addition to the lower-dose subgroup we evaluated.…”

“…Jolobe mentions that findings of lower GI bleeding risk associated with standard-dose apixaban vs warfarin would be contrary to ARISTOTLE randomized clinical trial findings. We would like to point out that relevant observational studies (including ARISTOPHANES) capture patient outcomes in routine clinical practice, wherein warfarin management was usually suboptimal [2,3,4,5]. In contrast, prospective interventional studies (including ARISTOTLE) were conducted in well-controlled environments [6,7,8].…”