Dabigatran, Rivaroxaban, and Warfarin in the Oldest Adults with Atrial Fibrillation in Taiwan

Abstract

Individuals with AF aged 85 and older who used reduced-dose dabigatran or reduced-dose rivaroxaban had statistically significantly lower all-cause mortality and cardiovascular mortality than those who used warfarin. Reduced-dose dabigatran was also associated with lower risk of intracranial hemorrhage than warfarin.

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

“…Dabigatran was associated with a similar ( Avgil-Tsadok et al., 2016 ; Deitelzweig et al., 2019 ; Alcusky et al., 2020 ) to significantly lower ( Wong et al., 2020 ) major bleeding risk, a similar ( Lai et al., 2018 ; Deitelzweig et al., 2019 ; Hohmann et al., 2019 ; Wong et al., 2020 ) to a significantly higher ( Avgil-Tsadok et al., 2016 ) gastrointestinal bleeding risk, and a significantly lower ( Avgil-Tsadok et al., 2016 ; Lai et al., 2018 ; Deitelzweig et al., 2019 ; Wong et al., 2020 ) intracranial bleeding risk as compared to warfarin in ≥75 in ≥75, ≥80 and ≥85 year old, ≥80 in ≥75, ≥80 and ≥85 year old, and ≥85-year-old AF patients ( Avgil-Tsadok et al., 2016 ; Lai et al., 2018 ; Deitelzweig et al., 2019 ; Hohmann et al., 2019 ; Alcusky et al., 2020 ; Wong et al., 2020 ). On the contrary, rivaroxaban was associated with a similar ( Alcusky et al., 2020 ) to significantly higher ( Deitelzweig et al., 2019 ; Wong et al., 2020 ) major bleeding risk, a similar ( Lai et al., 2018 ) to significantly higher ( Deitelzweig et al., 2019 ; Hohmann et al., 2019 ; Wong et al., 2020 ) gastrointestinal bleeding risk, and a similar ( Lai et al., 2018 ) to significantly lower ( Deitelzweig et al., 2019 ; Wong et al., 2020 ) intracranial bleeding risk as compared to warfarin in ≥75 in ≤75, ≤80 and ≤85 year old, ≥80 in ≤75, ≤80 and ≤85 year old, and ≥85 in ≤75, ≤80 and ≤85 year old year-old AF patients ( Lai et al., 2018 ; Deitelzweig et al., 2019 ; Hohmann et al., 2019 ; Alcusky et al., 2020 ; Wong et al., 2020 ). In a head-to-head comparison between NOACs in AF patients ≥80 years, apixaban was associated with a significantly lower risk of stroke/SE, major bleeding, gastrointestinal bleeding and mortality as compared to dabigatran and rivaroxaban, and even a significantly lower risk of intracranial bleeding as compared to rivaroxaban ( Deitelzweig et al., 2019 ).…”

“…In terms of effectiveness, NOACs had an equal stroke/SE risk as compared to VKAs in AF patients ≥75, ≥80, ≥85, and ≥90 years old ( Avgil-Tsadok et al., 2016 ; Lai et al., 2018 ; Giustozzi et al., 2019 ; Hohmann et al., 2019 ; Nishida et al., 2019 ; Mitchell et al., 2019 ; Russo et al., 2019 ; Shinohara et al., 2019 ; Alcusky et al., 2020 ). Some studies even described a significantly lower stroke/SE ( Deitelzweig et al., 2019 ; Kim et al., 2019 ) and ischemic stroke risk ( Mitchell et al., 2019 ; Deitelzweig et al., 2019 ; Chao et al., 2020 ), as opposed to a higher stroke/transient ischemic attack (TIA) risk in one small Italian study ( Poli et al., 2019 ) and a borderline increased ischemic stroke/TIA risk for apixaban in another study due to off-label underdosing ( Alcusky et al., 2020 ).…”

“…Moreover, in a subgroup analysis, results from observational studies investigating very old AF patients (≥80, ≥85, or ≥90 years old) were additionally included in the meta-analyses on the effectiveness and safety outcomes of interest. Seven additional observational cohort studies were included (four including AF patients ≥80 years old ( Deitelzweig et al., 2019 ; Kim et al., 2019 ; Russo et al., 2019 ; Shinohara et al., 2019 ), two including AF patients ≥85 years old ( Lai et al., 2018 ; Poli et al., 2019 ), and one including AF patients ≥90 years old) ( Giustozzi et al., 2019 ). Similar trends were observed, although the major bleeding risk was significantly lower for NOACs as compared to VKAs in AF patients ≥75, ≥80, ≥85, or ≥90 years old (HR 0.92, 95%CI [0.84-0.998], I² 89.1%) ( eFigures 4A–E ).…”

“…Even after additionally including seven observational studies investigating patients ≥80, ≥85, or ≥90 years old, consistent results were demonstrated, though the major bleeding risk was significantly lower for NOACs as compared to VKAs. However, safety differences between individual NOACs were identified, as increasing age above 75 years significantly interacted with the safety of dabigatran and rivaroxaban, illustrating non-inferior to inferior safety results in older AF patients, especially due to a higher gastrointestinal bleeding risk of both NOACs and a similar intracranial bleeding risk of rivaroxaban as compared to warfarin (Eikelboom et al, 2011;Halperin et al, 2014;Lin et al, 2015;Avgil-Tsadok et al, 2016;Lai et al, 2018;Deitelzweig et al, 2019;Hohmann et al, 2019;Wong et al, 2020). On the contrary, the superior safety profile of apixaban was preserved in older AF patients, with a significantly lower major, intracranial and gastrointestinal bleeding risk as compared to warfarin (Halvorsen et al, 2014;Lin et al, 2015;Deitelzweig et al, 2019;Hohmann et al, 2019;Alcusky et al, 2020;Wong et al, 2020).…”

Direct Anticoagulants Versus Vitamin K Antagonists in Patients Aged 80 Years or Older With Atrial Fibrillation in a “Real-world” Nationwide Registry: Insights From the FANTASIIA Study

“…[5][6][7][8][9] However, there is a paucity of "real-world" data on effectiveness and safety of these drugs, compared to VKAs, in octogenarian patients with AF. [10][11][12][13][14][15] Moreover, some studies have appointed the possibility of unclear safety in this particularly frail subgroup of patients in conditions of daily clinical practice. 16,17 The FANTASIIA registry (Spanish acronym for Atrial fibrillation: Influence of anticoagulation level and type on stroke and bleeding event incidence) is an observational, national, prospective, multicenter study that included patients aged 18 years or older with AF on anticoagulant treatment.…”